Bio

Bio


Dr. Muffly specializes in blood and marrow transplant and cellular therapies. Her interests include clinical research with a focus on improving outcomes in acute leukemia and blood and marrow transplantation.

Clinical Focus


  • acute leukemia
  • blood and marrow transplant
  • Hematology

Academic Appointments


Administrative Appointments


  • Senior Fellow, Lymphoma Program, University of Chicago (2011 - 2013)
  • Senior Fellow, Leukemia & Transplantation Program - University of Chicago (2011 - 2013)
  • Senior Fellow, Adolescent & Young Adult Clinic, University of Chicago (2012 - 2013)
  • Bone Marrow Transplant Fellow, Colorado Blood Cancer Institute, Denver CO (2013 - 2014)
  • Clinical Assistant Professor of Medicine, Stanford University (2014 - 2018)
  • Assistant Professor of Medicine, Stanford University (2018 - Present)

Honors & Awards


  • Herbert Armory Hare Honor Medical Society, Jefferson Medical College (2007)
  • Excellence in Teaching Award, Dartmouth Hitchcock Medical Center (2010)
  • Illinois Medical Oncology Society Fellow Research Award Recipient, . (2012)
  • NIH T32CA9566 Training Grant Recipient, . (2012)
  • Richard and Debra Gonzalez Fellowship Grant Recipient, University of Chicago (2012)
  • American Society of Blood & Marrow Transplantation Travel Grant Recipient, . (2013)
  • Conquer Cancer Foundation of ASCO Jane C Wright, MD Young Investigator Award, . (2013)

Boards, Advisory Committees, Professional Organizations


  • Member, American Society of Clinical Oncology (2014 - Present)
  • Member, American Society of Hematology (2014 - Present)

Professional Education


  • Board Certification: Hematology, American Board of Internal Medicine (2013)
  • Board Certification: Medical Oncology, American Board of Internal Medicine (2013)
  • Fellowship:University of Chicago (2013) IL
  • Medical Education:Jefferson Medical College (2007) PA
  • Internship:Dartmouth Hitchock Medical CenterNH
  • Residency:Dartmouth Hitchcock Medical CenterNH

Research & Scholarship

Current Research and Scholarly Interests


Dr. Muffly's interests include health services research and clinical trials with a focus on acute leukemia and blood and marrow transplantation.

Clinical Trials


  • Axicabtagene Ciloleucel Expanded Access Study Recruiting

    A multicenter, open-label expanded access protocol for the treatment of subjects with relapsed/refractory large B-cell lymphoma.

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  • CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Children or Young Adults With Recurrent or Refractory CD19 Positive B Acute Lymphoblastic Leukemia Recruiting

    This phase I trial studies the best dose and side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating children or young adults with CD19 positive B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD19/CD22-CAR T cells and chemotherapy may work better in treating children or young adults with B acute lymphoblastic leukemia.

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  • CD8+ Memory T-Cells as Consolidative Therapy After Donor Non-myeloablative Hematopoietic Cell Transplant in Treating Patients With Leukemia or Lymphoma Recruiting

    This phase II trial studies how well cluster of differentiation 8 (CD8)+ memory T-cells work as a consolidative therapy following a donor non-myeloablative hematopoietic cell transplant in treating patients with leukemia or lymphoma. Giving total lymphoid irradiation and anti-thymocyte globulin before a donor hematopoietic cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells, such as CD8+ memory T-cells, may boost this effect and may be an effective treatment to kill any cancer cells that may be left in the body (consolidative therapy).

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  • Efficacy of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma Recruiting

    The purpose of this study is to evaluate whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

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  • Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant Recruiting

    This phase II trial studies how well ibrutinib works in treating patients after a donor stem cell transplant for lymphoma that is not responding to treatment or has come back. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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  • MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC Recruiting

    This first time in human study is intended for men and women at least 18 years of age who have advanced lung cancer which has grown or returned after being treated. In particular, it is a study for subjects who have a blood test positive for HLA-A*02:01 and/or HLA-A*02:06 and a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose escalation trial that will evaluate 3 doses of transduced cells administered after a lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE A10ᶜ⁷⁹⁶T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by the T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with lung cancer. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose. Subjects will be seen frequently by the Study Physician right after receiving their T cells back and up to first 6 months. After that, subjects will be seen every three months. Subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion. If the T cells are found in the blood at five years, then the subjects will continue to be seen once a year until the T cells are no longer found in the blood for a maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the subject will be contacted by the Study Physician for the next 10 years. Subjects who have a confirmed response (or have stable disease for >4 months) but subsequent disease progression following the initial infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion. All subjects, completing or withdrawing from the Interventional Phase of the study, will enter a 15-year long-term follow-up phase for observation of delayed adverse events, All subjects will continue to be followed for overall survival during the long-term follow-up phase.

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  • Obinutuzumab in cGVHD After Allogeneic Peripheral Blood Stem Cell Transplantation Recruiting

    This research study is studying a drug called obinutuzumab as a means of preventing chronic Graft vs. Host Disease (cGVHD).

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  • Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors Recruiting

    This randomized phase III trial studies how well standard-dose combination chemotherapy works compared to high-dose combination chemotherapy and stem cell transplant in treating patients with germ cell tumors that have returned after a period of improvement or did not respond to treatment. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim or pegfilgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. It is not yet known whether high-dose combination chemotherapy and stem cell transplant are more effective than standard-dose combination chemotherapy in treating patients with refractory or relapsed germ cell tumors.

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  • Study of Quality of Life in Older vs. Younger Adult Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndromes Recruiting

    This is a multi-center, Phase II, cross-sectional study comparing quality of life (QOL) as assessed by patient-reported outcomes (PROs) in older (≥65 years) adults vs younger (55-64 years) undergoing allogeneic hematopoietic cell transplantation (HCT) for myelodysplastic syndromes (MDS).

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  • Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation Recruiting

    The purpose of this study is to evaluate whether addition of a low dose of total body irradiation (TBI) to a standard preparation for transplant [total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG)] conditioning will help to augment donor chimerism without reducing tolerability of this regimen or increasing the risk of graft-vs-host disease (GVHD)

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  • A Study of Ruxolitinib in Combination With Corticosteroids for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease (REACH1) Not Recruiting

    The purpose of this study is to assess the efficacy of ruxolitinib in combination with corticosteroids in subjects with Grades II to IV steroid-refractory acute graft-versus-host disease (GVHD).

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • A Trial of the FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor Gilteritinib Administered as Maintenance Therapy Following Allogeneic Transplant for Patients With FLT3/Internal Tandem Duplication (ITD) Acute Myeloid Leukemia (AML) Not Recruiting

    The purpose of this study is to compare relapse-free survival between participants with FLT3/ITD AML in first morphologic complete remission (CR1) who undergo hematopoietic stem cell transplant (HCT) and are randomized to receive gilteritinib or placebo beginning after the time of engraftment for a two year period.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Calcineurin Inhibitor-Free Interventions for Prevention of Graft-versus-Host Disease (BMT CTN 1301) Not Recruiting

    The study is designed as a three arm randomized Phase III, multicenter trial comparing two calcineurin inhibitor (CNI)-free strategies for Graft-versus-Host Disease (GVHD) prophylaxis to standard tacrolimus and methotrexate (Tac/Mtx) in patients with hematologic malignancies undergoing myeloablative conditioning hematopoietic stem cell transplantation.

    Stanford is currently not accepting patients for this trial.

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  • Donor Regulatory T Cells in Treating Patients With Visceral Acute Graft-versus-Host Disease After Stem Cell Transplant Not Recruiting

    This phase I trial studies the side effects and best dose of donor regulatory T cells in treating patients with graft-versus-host disease affecting the liver or gastrointestinal organs (visceral) within 100 days (acute) after undergoing a stem cell transplant. Graft-versus-host disease occurs when donor immune cells infused in a stem cell transplant attack the gut, skin, liver, or other organ systems of the patient. Regulatory T cells are a type of immune cell that may be able to reduce the attack of the donor's immune cells on the patient's normal cells and help treat graft-vs-host disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Joanne Otani, 650-721-2372.

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  • Expanded Access Protocol for Tabelecleucel for Patients With Epstein-Barr Virus-Associated Viremia or Malignancies Not Recruiting

    The primary objective of this protocol is to provide expanded access to tabelecleucel to participants with Epstein-Barr virus-associated diseases and malignancies for whom there are no other appropriate therapeutic options, and who are not eligible to enroll in clinical studies designed to support the development and registration of tabelecleucel.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Subjects With New Onset cGVHD Not Recruiting

    To evaluate the safety and efficacy of ibrutinib in combination with prednisone in subjects with newly diagnosed moderate to severe cGVHD.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Post T-plant Infusion of Allogeneic Cytokine Induced Killer Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders Not Recruiting

    Allogeneic stem cell transplantation (transplant of blood cells from another individual) is a treatment option for patients with Myelodysplasia or Myeloproliferative Disorders. During the course of this study, we will attempt to learn whether a particular type of blood cell, called a Cytokine Induced Killer (CIK) cell may add benefit to allogeneic stem cell transplantation. CIK cells are present in small quantities in the bloodstream but their numbers can be expanded after a brief period of nurturing in a laboratory.

    Stanford is currently not accepting patients for this trial. For more information, please contact Physician Referrals, 650-723-0822.

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  • Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Not Recruiting

    The primary objective of phase 1 is to evaluate the safety of axicabtagene ciloleucel and atezolizumab combination regimens. The primary objective of phase 2 is to evaluate the efficacy of axicabtagene ciloleucel and atezolizumab, as measured by complete response rate in subjects with refractory diffuse large B-cell lymphoma (DLBCL).

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Stanford Letter or Traditional Advance Directive in Advance Care Planning in Patients Undergoing Bone Marrow Transplant Not Recruiting

    The purpose of the proposed research study is to evaluate whether bone marrow transplant patients prefer the Stanford letter advance care planning tool to the standard Advance directive. Completion of advance care planning prior to BMT is very important, but not often done. The investigators believe that the Stanford Letter will be preferred by patients and will allow them to feel more comfortable and share more of their wishes with family members and the medical team.

    Stanford is currently not accepting patients for this trial. For more information, please contact VJ PERIYAKOIL, MD, 650-493-5000 Ext. 61925.

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Publications

All Publications


  • Hematopoietic Cell Transplantation in Young Adult Acute Lymphoblastic Leukemia: A United States Population-Level Analysis. Journal of adolescent and young adult oncology Muffly, L., Li, Q., Alvarez, E., Kahn, J., Winestone, L., Cress, R., Penn, D. C., Keegan, T. H. 2019

    Abstract

    In this population-based evaluation of adolescents and young adults (AYA) acute lymphoblastic leukemia (ALL), we describe patterns of care (POC) and outcomes regarding hematopoietic cell transplantation (HCT) in first complete remission (CR1). Data were abstracted from the 2013 United States Surveillance, Epidemiology, and End Results POC study; newly diagnosed AYA ALL were included. Multivariable logistic regression evaluated associations with HCT in CR1; Cox proportional hazards regression evaluated survival associations. Of 399 AYAs with ALL included, 102 (28.5%) underwent HCT in CR1. High-risk cytogenetics (odds ratio [OR]=4.86, 95% confidence interval [CI]=3.02-7.83) and hyper-cyclophosphamide, vincristine, adriamycin, and dexamethasone (CVAD) induction (OR=1.84, 95% CI=1.07-3.16) were associated with HCT in CR1. Two-year cumulative incidence of relapse, relapse-free survival (RFS), and overall survival (OS) of the entire cohort were 28.3% (95% CI=23.4-33.4), 69.3% (95% CI=63.6-74.3%), and 84.1% (95% CI=79.7-87.5), respectively. Two-year RFS was significantly higher in patients receiving CR1 HCT relative to chemotherapy (83.6%, 95% CI=72.6-90.5% vs. 64.3%, 95% CI=57.5-70.3), but no difference was seen in 2-year OS (88.9%, 95% CI=80.8-93.7 vs. 82.5%, 95% CI=77.2-86.7). Treatment at a nonteaching hospital was independently associated with inferior OS (hazard ratio=2.15, 95% CI=1.23-3.76). Although the ALL landscape is changing, these data provide a snapshot of the use and outcomes of HCT for AYA ALL across the United States.

    View details for DOI 10.1089/jayao.2018.0140

    View details for PubMedID 30657424

  • Acute leukemia in a patient with 15q overgrowth syndrome. American journal of medical genetics. Part A Bodle, E. E., Gupta, R., Cherry, A. M., Muffly, L., Manning, M. A. 2019

    Abstract

    Overgrowth syndromes are rare genetic conditions which present as global or segmental hyperplasia and are sometimes associated with increased risk of malignancy. Trisomy of the terminal portion of 15q which includes the IGFR1 gene, produces a rare overgrowth phenotype that has been termed 15q overgrowth syndrome (15q OGS). Upregulation of IGF1R has long been implicated in oncogenesis of multiple cancer types, including acute leukemias, and has been shown to render cells more susceptible to other transforming events. To date, too few cases of 15q OGS have been reported to identify any cancer predisposition. We present a case of a 34-year-old female with intellectual disability, macrocephaly, and subtle dysmorphic features who was diagnosed with mixed phenotype acute leukemia (lymphoid and myeloid). Prior to initiation of therapy she was referred to medical genetics for further evaluation and was identified as having a chromosomal translocation resulting in a partial trisomy of chromosome 15q, consistent with 15q OGS. A review of the literature for cases of malignancy in individuals with increased copy number of 15q revealed only one other reported patient. Given the small number of reported individuals, we cannot rule out an increased risk of cancer associated with this chromosomal overgrowth syndrome. Although concerns have been raised regarding treatment feasibility in the setting of chromosomal disorders, the reported patient underwent successful treatment with allogeneic hematopoietic stem-cell transplant.

    View details for DOI 10.1002/ajmg.a.61115

    View details for PubMedID 30861314

  • Decreased Early Mortality in Young Adult Patients With Acute Lymphoblastic Leukemia Treated at Specialized Cancer Centers in California. Journal of oncology practice Alvarez, E. M., Malogolowkin, M., Li, Q., Brunson, A., Pollock, B. H., Muffly, L., Wun, T., Keegan, T. H. 2019: JOP1800264

    Abstract

    PURPOSE:: Studies suggest that patients with acute lymphoblastic leukemia (ALL) have superior survival when treated at specialized cancer centers (SCCs). However, the association of early mortality (< 60 days) with location of initial care, sociodemographic factors, and complications has not been evaluated in pediatric and young adult (YA) patients with ALL.METHODS:: Using the California Cancer Registry linked to hospitalization data, we identified pediatric and YA patients with ALL who received inpatient leukemia treatment between 1991 and 2014. Patients were classified as receiving all or part/none of their care at an SCC (Children's Oncology Group- or National Cancer Institute-designated cancer center). Propensity scores were created for treatment at an SCC in each age group. Multivariable, inverse probability-weighted Cox proportional hazards regression models identified factors associated with early mortality. Results are presented as hazard ratios (HRs) and 95% CIs.RESULTS:: Among 6,531 newly diagnosed pediatric (≤ 18 years) and YA (19 to 39 years of age) patients with ALL, 1.6% of children and 5.4% of YAs died within 60 days of diagnosis. Most children received all of their care at an SCC (n = 4,752; 85.7%) compared with 35.5% of YAs (n = 1,779). Early mortality rates were lower in pediatric patients and those receiving all care at an SCC (pediatric: all, 1.5%, v part/none, 2.4%; P = .049; YAs: all, 3.2%, v part/none, 6.6%; P = .001). However, in adjusted models, receiving all care at an SCC was associated with significantly lower early mortality in YAs (HR, 0.51; 95% CI, 0.32 to 0.81), but not in pediatric patients (HR, 0.77; 95% CI, 0.47 to 1.25).CONCLUSION:: YAs with ALL experience significant reductions in early mortality after treatment at SCCs.

    View details for DOI 10.1200/JOP.18.00264

    View details for PubMedID 30849003

  • Does Treatment Setting Matter? Evaluating Resource Utilization for Adolescents Treated in Pediatric vs Adult Cancer Institutions. Journal of the National Cancer Institute Parsons, H. M., Muffly, L., Alvarez, E. M., Keegan, T. H. 2019; 111 (3): 224–25

    View details for DOI 10.1093/jnci/djy123

    View details for PubMedID 30053066

  • Health Care Utilization and Intensity at End of Life is High Amongst Adults Who Relapse Following Allogeneic Hematopoietic Cell Transplantation Langston, J., Sundaram, V., Periyakoil, V., Muffly, L. ELSEVIER SCIENCE INC. 2019: 506
  • Nonmyeloablative Allogeneic Transplantation Using TLI-ATG Conditioning for Lymphoid and Myeloid Malignancies: Mature Follow-up from a Large, Single Institution Cohort Spinner, M. A., Kennedy, V. E., Tamaresis, J. S., Lavori, P. W., Elder, L. V., Arai, S., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W., Hoppe, R. T., Strober, S., Lowsky, R. AMER SOC HEMATOLOGY. 2018
  • Impact of Myeloablative Total Body Irradiation Versus Chemotherapy on Late Effects and Survival Among Adolescent and Young Adult Survivors of Hematopoietic Cell Transplantation for Acute Leukemia: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis Lee, C. J., Kim, S., Tecca, H. R., Brazauskas, R., Battiwalla, M., Buchbinder, D. K., Flowers, M. D., Phelan, R., Shaw, B. E., Muffly, L. S. AMER SOC HEMATOLOGY. 2018
  • Medical Conditions Among Survivors of Adolescent and Young Adult Non-Hodgkin Lymphoma (NHL), Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML) Keegan, T. M., Muffly, L. S., Li, Q., Alvarez, E., Brunson, A. M., Malogolowkin, M., Wun, T. AMER SOC HEMATOLOGY. 2018
  • Health Care Utilization Is High Amongst Adults Who Relapse Following Allogeneic Hematopoietic Cell Transplantation Langston, J., Sundaram, V., Periyakoil, V., Muffly, L. S. AMER SOC HEMATOLOGY. 2018
  • Disparities in Cancer-Related Mortality and Long-Term Survival in Adolescent and Young Adults with Hodgkin Lymphoma: A Population-Level Analysis across the United States Kahn, J. M., Keegan, T. M., Alvarez, E., Muffly, L. S., Parsons, H., Winestone, L. E., Bleyer, A. AMER SOC HEMATOLOGY. 2018
  • Hematopoietic Cell Transplantation in First Remission Amongst Adolescent and Young Adult Acute Lymphoblastic Leukemia: A Population-Level Analysis across the United States Muffly, L. S., Li, Q., Alvarez, E., Kahn, J. M., Winestone, L. E., Cress, R., Penn, D., Keegan, T. M. AMER SOC HEMATOLOGY. 2018
  • 1 Study of CD19/CD22 Bispecific Chimeric Antigen Receptor (CAR) Therapy in Children and Young Adults with B Cell Acute Lymphoblastic Leukemia (ALL) Schultz, L. M., Davis, K. L., Baggott, C., Chaudry, C., Marcy, A., Mavroukakis, S., Sahaf, B., Kong, K. A., Muffly, L. S., Kim, S., Meyer, E. H., Fry, T. J., Qin, H., Miklos, D. B., Mackall, C. L. AMER SOC HEMATOLOGY. 2018
  • Phase I Experience with a Bi-Specific CAR Targeting CD19 and CD22 in Adults with B-Cell Malignancies Hossain, N., Sahaf, B., Abramian, M., Spiegel, J. Y., Kong, K., Kim, S., Mavroukakis, S., Oak, J., Natkunam, Y., Meyer, E. H., Frank, M. J., Feldman, S. A., Long, S. R., Qin, H., Fry, T. J., Muffly, L. S., Mackall, C. L., Miklos, D. B. AMER SOC HEMATOLOGY. 2018
  • Elevated Axicabtagene Ciloleucel (CAR-19) Expansion By Immunophenotyping Is Associated with Toxicity in Diffuse Large B-Cell Lymphoma Spiegel, J. Y., Sahaf, B., Hossain, N., Frank, M. J., Claire, G., Abramian, M., Latchford, T., Villa, B., Cancilla, J., Oak, J., Natkunam, Y., Long, S. R., Arai, S., Johnston, L. J., Lowsky, R., Meyer, E. H., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W., Kong, K. A., Mackall, C. L., Miklos, D. B. AMER SOC HEMATOLOGY. 2018
  • Care at specialized cancer centers among young adults with acute lymphoblastic leukemia in California. Leukemia & lymphoma Alvarez, E., Muffly, L., Li, Q., Brunson, A., Wun, T., Chamberlain, L., Keegan, T. 2018; 59 (10): 2482–84

    View details for DOI 10.1080/10428194.2018.1427856

    View details for PubMedID 29424251

  • Treatment of young adults with Philadelphia-negative acute lymphoblastic leukemia and lymphoblastic lymphoma: Hyper-CVAD vs. pediatric-inspired regimens AMERICAN JOURNAL OF HEMATOLOGY Siegel, S. E., Advani, A., Seibel, N., Muffly, L., Stock, W., Luger, S., Shah, B., DeAngelo, D. J., Freyer, D. R., Douer, D., Johnson, R. H., Hayes-Lattin, B., Lewis, M., Jaboin, J. J., Coccia, P. F., Bleyer, A. 2018; 93 (10): 1254–66

    Abstract

    For young adults with acute lymphoblastic leukemia, pediatric-based regimens are likely to provide the following when compared to hyper-CVAD regimens: better disease control, less hospitalization time, diminished acute toxicities, decreased financial cost, more quality-adjusted life years, and fewer adverse late effects, such as infertility, myelodysplasia, and second malignant neoplasms. There are also reasons to expect less cardiac and cognitive dysfunction after pediatric regimens. The improved quality and quantity of life associated with pediatric regimens renders them preferable to hyper-CVAD regimens for the treatment of Philadelphia-negative B-precursor or T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma in young adults.

    View details for DOI 10.1002/ajh.25229

    View details for Web of Science ID 000447533300016

    View details for PubMedID 30058716

  • A Three-Step Letter Advance Directive Procedure to Facilitate Patient-Proxy Alignment in Advance Care Planning JOURNAL OF PALLIATIVE MEDICINE Alagappan, M., Richardson, M. T., Schoen, M. K., Muffly, L., Tierney, K., Jenkins, P., Neri, E., Kraemer, H. C., Periyakoil, V. S. 2018

    Abstract

    Little is known about the extent of alignment between hematopoietic stem cell transplant (HSCT) patients and their healthcare proxies with respect to advance care planning (ACP).To determine if a structured three-step process using the letter advance directive (LAD) could (1) allow for the differences in opinion between patient-proxy dyads to surface and (2) help bridge preexisting discordance about specific treatment choices.Blinded to each other, the HSCT patient (LAD-1) and proxy (LAD-2) each completed the LAD (step 1). They unmasked, compared LAD-1 and LAD-2, and discussed their choices (step 2). They completed a final letter directive (LAD-3) by consensus (step 3). Settings/Participants: Convenience sample of eighty dyads (patient and proxy) at a regional HSCT referral center.The mean patient-proxy concordance was 72.9% for the 12 questions in the LAD. Wanting to be pain free at the end of life was the statement with the most amount of agreement (88.75% in LAD-1, 91.25% in LAD-2, and 90% in LAD-3). Patient-proxy dyads had notable discordance related to specific treatments. The highest discordance was related to ventilator support (46.3% of patients refused it, while 58.8% of proxies refused on behalf of the patient). Overall, proxies were more likely than patients to opt in for dialyses and hospice care but more likely to opt out for cardiac resuscitation and sedation to palliate refractory symptoms. On open discussion, patient-proxy discordance mostly resolved in favor of the patient.The ACP process should allow for patient-proxy differences to surface, facilitate a discussion about the granular details with the goal of reaching consensus. Our three-step approach using the LAD is an effective way to identify areas of patient-proxy concordance and discordance about specific treatment preferences. A structured patient-proxy discussion using the LAD helped reconcile discordance and most often in favor of a patient's original wishes.

    View details for DOI 10.1089/jpm.2018.0150

    View details for Web of Science ID 000445343200001

    View details for PubMedID 30247088

  • End-of-Life Care Intensity in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation: A Population-Level Analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Johnston, E. E., Muffly, L., Alvarez, E., Saynina, O., Sanders, L. M., Bhatia, S., Chamberlain, L. J. 2018: JCO2018780957

    Abstract

    Purpose Intensity of end-of-life care receives much attention in oncology because of concerns that high-intensity care is inconsistent with patient goals, leads to worse caregiver outcomes, and is expensive. Little is known about such care in those undergoing allogeneic hematopoietic cell transplantation (HCT), a population at high risk for morbidity and mortality. Patients and Methods We conducted a population-based analysis of patients who died between 2000 and 2013, within 1 year of undergoing an inpatient allogeneic HCT using California administrative data. Previously validated markers of intensity were examined and included: hospital death, intensive care unit (ICU) admission, and procedures such as intubation and cardiopulmonary resuscitation at end of life. Multivariable logistic regression models determined clinical and sociodemographic factors associated with: hospital death, a medically intense intervention (ICU admission, cardiopulmonary resuscitation, hemodialysis, intubation), and ≥ two intensity markers. Results Of the 2,135 patients in the study population, 377 were pediatric patients (age ≤ 21 years), 461 were young adults (age 22 to 39 years), and 1,297 were adults (age ≥ 40 years). The most common intensity markers were: hospital death (83%), ICU admission (49%), and intubation (45%). Medical intensity varied according to age, underlying diagnosis, and presence of comorbidities at time of HCT. Patients with higher-intensity end-of-life care included patients age 15 to 21 years and 30 to 59 years, patients with acute lymphoblastic leukemia, and those with comorbidities at time of HCT. Conclusion Patients dying within 1 year of inpatient allogeneic HCT are receiving medically intense end-of-life care with variations related to age, underlying diagnosis, and presence of comorbidities at time of HCT. Future studies need to determine if these patterns are consistent with patient and family goals.

    View details for DOI 10.1200/JCO.2018.78.0957

    View details for PubMedID 30183467

  • Detection of Measurable Residual Disease by Next-Generation Sequencing in Paired Blood and Bone Marrow Samples from Patients with Lymphoid Malignancies Miklos, D., Muffly, L., Lee, L., Crossley, B. CIG MEDIA GROUP, LP. 2018: S295–S296
  • Minimal Residual Disease Monitoring of Acute Lymphoblastic Leukemia by High-Throughput Sequencing of the Peripheral Blood: Case Examples and Literature Review Muffly, L. CIG MEDIA GROUP, LP. 2018: S53–S55
  • Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma following CAR T-cell therapy. Leukemia & lymphoma Hossain, N. M., Dahiya, S., Le, R., Abramian, A. M., Kong, K. A., Muffly, L. S., Miklos, D. B. 2018: 1–4

    View details for DOI 10.1080/10428194.2018.1474463

    View details for PubMedID 29966461

  • Pediatric-Inspired Treatment Regimens for Adolescents and Young Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia A Review JAMA ONCOLOGY Siegel, S. E., Stock, W., Johnson, R. H., Advani, A., Muffly, L., Douer, D., Reed, D., Lewis, M., Freyer, D. R., Shah, B., Luger, S., Hayes-Lattin, B., Jaboin, J. J., Coccia, P. F., DeAngelo, D. J., Seibel, N., Bleyer, A. 2018; 4 (5): 725–34

    Abstract

    The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL.All but 2 of 25 published comparisons of outcomes with pediatric and adult regimens for ALL and LBL in AYAs and 1 meta-analysis favor the pediatric regimen. After more than a half-century of clinical trials of the pediatric regimens, including at least 160 phase 3 trials in the United States, the pediatric regimens have become far more complex than most adult regimens. Asparaginase, a critical component of the pediatric regimens, is more difficult to administer to AYAs (and older patients) but nonetheless has a favorable benefit to toxicity ratio for AYAs. A dramatic reduction in outcome of ALL and LBL during the AYA years (the "survival cliff") is coincident with similar reductions in proportions of AYAs referred to academic centers and enrolled on clinical trials (the "accrual cliff" and "referral cliff").The accumulating data increasingly support treating AYAs with ALL and LBL with a pediatric-inspired regimen or an approved institutional or national clinical trial tailored for this patient group. A need to develop clinical trials specifically for AYAs and to encourage their participation is paramount, with a goal to improve both the quantity and quality of survival.

    View details for DOI 10.1001/jamaoncol.2017.5305

    View details for Web of Science ID 000431868700023

    View details for PubMedID 29450465

  • Decreased Early Mortality Associated With the Treatment of Acute Myeloid Leukemia at National Cancer Institute-Designated Cancer Centers in California CANCER Ho, G., Wun, T., Muffly, L., Li, Q., Brunson, A., Rosenberg, A. S., Jonas, B. A., Keegan, T. M. 2018; 124 (9): 1938–45

    Abstract

    To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML).Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis).Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs.The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society.

    View details for DOI 10.1002/cncr.31296

    View details for Web of Science ID 000430464800011

    View details for PubMedID 29451695

  • Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukemia: a population-based study BLOOD ADVANCES Muffly, L., Alvarez, E., Lichtensztajn, D., Abrahao, R., Gomez, S., Keegan, T. 2018; 2 (8): 895–903

    Abstract

    Adolescents and young adults (AYAs, 15-39 years) with acute lymphoblastic leukemia (ALL) represent a heterogeneous population who receive care in pediatric or adult cancer settings. Using the California Cancer Registry, we describe AYA ALL patterns of care and outcomes over the past decade. Sociodemographics, treatment location, and front-line therapies administered to AYAs diagnosed with ALL between 2004 and 2014 were obtained. Cox regression models evaluated associations between ALL setting and regimen and overall survival (OS) and leukemia-specific survival (LSS) for the entire cohort, younger AYA (<25 years), and AYAs treated in the adult cancer setting only. Of 1473 cases, 67.7% were treated in an adult setting; of these, 24.8% received a pediatric ALL regimen and 40.7% were treated at a National Cancer Institute (NCI)-designated center. In multivariable analyses, front-line treatment in a pediatric (vs adult) setting (OS HR = 0.53, 95% confidence interval [CI], 0.37-0.76; LSS HR = 0.51, 95% CI, 0.35-0.74) and at an NCI/Children's Oncology Group (COG) center (OS HR = 0.80, 95% CI, 0.66-0.96; LSS HR = 0.80, 95% CI, 0.65-0.97) were associated with significantly superior survival. Results were similar when analyses were limited to younger AYAs. Outcomes for AYAs treated in an adult setting did not differ following front-line pediatric or adult ALL regimens. Our population-level findings demonstrate that two-thirds of AYAs with newly diagnosed ALL are treated in an adult cancer setting, with the majority receiving care in community settings. Given the potential survival benefits, front-line treatment of AYA ALL at pediatric and/or NCI/COG-designated cancer centers should be considered.

    View details for DOI 10.1182/bloodadvances.2017014944

    View details for Web of Science ID 000430753300009

    View details for PubMedID 29669756

    View details for PubMedCentralID PMC5916002

  • Infusion of donor-derived CD8(+) memory T cells for relapse following allogeneic hematopoietic cell transplantation BLOOD ADVANCES Muffly, L., Sheehan, K., Armstrong, R., Jensen, K., Tate, K., Rezvani, A. R., Miklos, D., Arai, S., Shizuru, J., Johnston, L., Meyer, E., Weng, W., Laport, G. G., Negrin, R. S., Strober, S., Lowsky, R. 2018; 2 (6): 681–90

    Abstract

    Murine models showed that CD8+CD44hi memory T (TM) cells could eradicate malignant cells without inducing graft-versus-host disease (GVHD). We evaluated the feasibility and safety of infusing freshly isolated and purified donor-derived phenotypic CD8+ TM cells into adults with disease relapse after allogeneic hematopoietic cell transplantation (HCT). Phenotypic CD8 TM cells were isolated after unmobilized donor apheresis using a tandem immunomagnetic selection strategy of CD45RA depletion followed by CD8+ enrichment. Fifteen patients received CD8+ TM cells at escalating doses (1 × 106, 5 × 106, or 10 × 106 cells per kg). Thirteen received cytoreduction before CD8+ TM cell infusion, and 9 had active disease at the time of infusion. Mean yield and purity of the CD8+ TM infusion were 38.1% and 92.8%, respectively; >90% had CD8+ T effector memory phenotype, cytokine expression, and secretion profile. No adverse infusional events or dose-limiting toxicities occurred; GVHD developed in 1 patient (grade 2 liver). Ten patients (67%) maintained or achieved response (7 complete response, 1 partial response, 2 stable disease) for at least 3 months after infusion; 4 of the responders had active disease at the time of infusion. With a median follow-up from infusion of 328 days (range, 118-1328 days), median event-free survival and overall survival were 4.9 months (95% confidence interval [CI], 1-19.3 months) and 19.6 months (95% CI, 5.6 months to not reached), respectively. Collection and enrichment of phenotypic CD8+ TM cells is feasible, well tolerated, and associated with a low incidence of GVHD when administered as a manipulated infusion of donor lymphocytes in patients who have relapsed after HCT. This trial was registered at www.clinicaltrials.gov as #NCT01523223.

    View details for DOI 10.1182/bloodadvances.2017012104

    View details for Web of Science ID 000428386900010

    View details for PubMedID 29572391

    View details for PubMedCentralID PMC5873230

  • Another reason to encourage psychosocial risk assessment in hematopoietic cell transplantation. Bone marrow transplantation Muffly, L., Artz, A. 2018

    View details for DOI 10.1038/s41409-018-0143-3

    View details for PubMedID 29588499

  • Phase I/II Trial for Patients with Advanced Hematologic Malignancies Undergoing Myeloablative Allogeneic HCT with a T Cell Depleted Graft with Infusion of Conventional T Cells and Regulatory T Cells Meyer, E., Laport, G. G., Tantsura, I., Tang, S., Sahaf, B., Rangarajan, K., Armstrong, R., Tate, K., Tudisco, C., Sheehan, K., Arai, S., Johnston, L., Muffly, L., Lowsky, R., Rezvani, A., Weng, W., Miklos, D., Negrin, R. S. ELSEVIER SCIENCE INC. 2018: S145
  • Management of Acute Lymphoblastic Leukemia in Young Adults CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY Muffly, L., Reizine, N., Stock, W. 2018; 16 (2): 138–46

    Abstract

    Substantial interest in acute lymphoblastic leukemia (ALL) in young adults (YAs) and investigations focused on this patient population have resulted in therapeutic advancements that are changing the management paradigm and improving outcomes. The pediatric ALL approach is feasible and effective when administered by medical oncologists. Advanced diagnostics and minimal residual disease measurements aid in prognostication and have resulted in shifting recommendations regarding allogeneic hematopoietic cell transplant in first remission. Blinatumomab, inotuzumab, and chimeric antigen receptor T-cell therapies are transforming the treatment of relapsed/refractory ALL. This comprehensive review of the current management of ALL in YAs summarizes recent scientific developments and clinical trial findings related to ALL biology, frontline management approaches, novel therapies, and supportive care specific to this patient population. Finally, a practical guide to modern YA management for practicing clinicians is provided.

    View details for Web of Science ID 000430661400008

    View details for PubMedID 29741514

  • Advance Directive Utilization is Associated with Less Aggressive End-of-Life Care in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Cappell, K., Sundaram, V., Park, A., Shiraz, P., Gupta, R., Jenkins, P., Periyakoil, V. S., Muffly, L. 2018

    Abstract

    Background Allogeneic hematopoietic cell transplantation (HCT) is associated with significant morbidity and mortality, making advance care planning (ACP) and management especially important in this patient population. A paucity of data exists on the utilization of ACP amongst allogeneic HCT recipients, and the relationship between ACP and intensity of health care utilization in these patients. Methods We performed a retrospective review of patients receiving allogeneic HCT at our institution from 2008 to 2015 who had subsequently died following HCT. Documentation and timing of advance directive (AD) completion were abstracted from the electronic medical record. Outcomes of interest included (a) utilization of intensive care unit level of care (ICU) at (i) any time point following HCT, (ii) within 30 days of death, (iii) within 14 days of death, (b) use of mechanical ventilation at any time point following HCT, and (c) location of death. Univariate logistic regression was performed to explore associations between AD completion and each outcome. Results Of the 1031 patients who received allogeneic HCT during the study period, there were 422 (41%) decedents who are included in the analysis. Forty-four percent had AD documentation prior to death. A majority of patients (69%) indicated that if terminally ill, they did not wish to be subjected to life-prolonging treatment attempts. Race/ethnicity was significantly associated with AD documentation, with Non-Hispanic White patients documenting ADs more frequently (51%) compared to Hispanic (22%) or Asian patients (35%); p= 0.0007. Patients with AD were less likely to utilize the ICU during the transplant course (41% for patients with AD versus 52% of patients without AD; p= 0.03) and also were less likely to receive mechanical ventilation at any point following transplantation (21% versus 37%; p<0.001). AD documentation was also associated with decreased ICU utilization at the end-of-life; relative to patients without AD, patients with AD were more likely to die at home or in hospital as opposed to in the ICU (OR 0.44, 95% CI 0.27-0.72).ACP remains underutilized in allogeneic HCT. Adoption of a systematic practice to standardize AD documentation as part of allogeneic HCT planning has the potential to significantly reduce ICU utilization and mechanical ventilation while improving quality of care at end-of-life in HCT recipients.

    View details for DOI 10.1016/j.bbmt.2018.01.014

    View details for PubMedID 29371107

  • Inotuzumab ozogamicin: a CD22 mAb-drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia DRUG DESIGN DEVELOPMENT AND THERAPY Yurkiewicz, I. R., Muffly, L., Liedtke, M. 2018; 12: 2293–2300

    Abstract

    Despite improved rates of remission and cure in newly diagnosed adult acute lymphoblastic leukemia (ALL), the prognosis for patients with relapsed or refractory disease remains poor and the 5-year overall survival rate after relapse is under 10%. A recent paradigm shift has focused on the promise of targeted immunotherapy rather than standard chemotherapy, as ALL blast cells express a variety of antigens, and monoclonal antibodies may be developed to identify and destroy the leukemic cells. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. CD22 expression is detected on leukemic blasts in over 90% of patients with ALL. Based on promising results from preclinical studies, inotuzumab ozogamicin was tested in Phase 1/2 and Phase 3 clinical trials and it demonstrated improved complete remission rates, progression-free survival and overall survival in relapsed or refractory adult ALL compared to standard therapy. Ongoing studies are evaluating the value of inotuzumab ozogamicin when given in combination with chemotherapy as part of upfront treatment. This review discusses the drug's biochemical properties and mechanism of action, preclinical research outcomes, clinical trial results, adverse events and toxicities, drug approval and ongoing investigations.

    View details for DOI 10.2147/DDDT.S150317

    View details for Web of Science ID 000439928700001

    View details for PubMedID 30087554

    View details for PubMedCentralID PMC6063246

  • Allogeneic transplantation using TLI-ATG conditioning for Hodgkin lymphoma after failure of autologous transplantation. Blood advances Spinner, M. A., Advani, R. H., Hoppe, R. T., Lowsky, R., Muffly, L. S. 2018; 2 (13): 1547–50

    View details for DOI 10.1182/bloodadvances.2018021071

    View details for PubMedID 29970391

  • Coordination of Care in Survivorship After Treatment of Hematological Malignancies-The Journey is Not Over Yet. Current hematologic malignancy reports Lee, C. J., Muffly, L. S. 2017

    Abstract

    The number of adult survivors of hematologic malignancies is steadily growing. This population is at moderate to high risk for cancer survivorship issues including physical and psychosocial sequelae of intensive cancer therapies. Although cancer survivorship is a growing field in pediatric and solid tumor oncology, survivorship care and research has often been overlooked in the hematologic malignancies. In this review, we focus specifically on survivorship issues related to adult patients with hematologic malignancies and provide commentary on the role of cancer survivorship, proposed survivorship care models, and the economic and health policy obstacles associated with moving the cancer survivorship field forward in this very important patient population.

    View details for DOI 10.1007/s11899-017-0390-1

    View details for PubMedID 28534144

  • Pharmacologic maintenance strategies following allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Leukemia & lymphoma Lee, C. J., Shiraz, P., Muffly, L. 2017; 58 (3): 516-527

    Abstract

    The use of pharmacologic agents to maintain remission following allogeneic hematopoietic cell transplantation (HCT) is a topic of increasing interest and exploration for patients with high-risk acute myeloid leukemia (AML). This review details published and ongoing studies focused on post-transplant pharmacologic maintenance for AML. While early phase studies have demonstrated the safety and tolerability of various maintenance approaches following HCT, the results of several ongoing randomized prospective studies will be required to determine the clinical efficacy needed to expand this approach from experimental to standard of care.

    View details for DOI 10.1080/10428194.2016.1205744

    View details for PubMedID 27685315

  • My Patient, the Superhero. Journal of clinical oncology Muffly, L. 2017: JCO2016696005-?

    View details for DOI 10.1200/JCO.2016.69.6005

    View details for PubMedID 28165900

  • HLA-mismatched unrelated donor transplantation using TLI-ATG conditioning has a low risk of GVHD and potent antitumor activity. Blood advances Spinner, M. A., Fernández-Viña, M., Creary, L. E., Quinn, O., Elder, L., Arai, S., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Shizuru, J. A., Weng, W. K., Laport, G. G., Strober, S., Lowsky, R., Rezvani, A. R. 2017; 1 (17): 1347–57

    Abstract

    Many patients lack a fully HLA-matched donor for hematopoietic cell transplantation (HCT), and HLA mismatch is typically associated with inferior outcomes. Total lymphoid irradiation and antithymocyte globulin (TLI-ATG) is a nonmyeloablative conditioning regimen that is protective against graft-versus-host disease (GVHD), and we hypothesized that the protective effect would extend beyond HLA-matched donors. We report outcomes for all consecutively transplanted patients at Stanford University from December 2001 through May 2015 who received TLI-ATG conditioning and HCTs from 8 to 9 out of 10 HLA-mismatched unrelated donors (MMUDs, N = 72) compared with 10 out of 10 HLA-matched unrelated donors (MUDs, N = 193). The median age of the patients was 60 years with a median follow-up of 2 years, and there was a similar distribution of lymphoid and myeloid malignancies in both cohorts. There were no significant differences between MMUD and MUD cohorts in overall survival (46% vs 46% at 5 years, P = .86), disease-free survival (38% vs 28% at 5 years, P = .25), nonrelapse mortality (17% vs 12% at 2 years, P = .34), acute GVHD grades III-IV (6% vs 3% at day +100, P = .61), or chronic GVHD (39% vs 35% at 5 years, P = .49). There was a trend toward less relapse in the MMUD cohort (45% vs 60% at 5 years, hazard ratio: 0.71, P = .094), which was significant for patients with lymphoid malignancies (29% vs 57% at 5 years, hazard ratio: 0.55, P = .044). Achieving full donor chimerism was strongly associated with lower relapse rates. TLI-ATG conditioning may overcome the traditionally poorer outcome associated with HLA-mismatched donors and may be particularly well suited for patients with lymphoid malignancies who lack HLA-matched donors.

    View details for DOI 10.1182/bloodadvances.2017007716

    View details for PubMedID 29296777

    View details for PubMedCentralID PMC5727975

  • Adoption of Pediatric-Inspired Acute Lymphoblastic Leukemia Regimens by Adult Oncologists Treating Adolescents and Young Adults: A Population-Based Study CANCER Muffly, L., Lichtensztajn, D., Shiraz, P., Abrahao, R., McNeer, J., Stock, W., Keegan, T., Gomez, S. L. 2017; 123 (1): 122-130

    Abstract

    Studies have demonstrated superior outcomes for adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) who are treated using pediatric versus adult therapeutic regimens. To the best of our knowledge, whether adult oncologists in the United States have adopted this approach to ALL in AYA patients is currently unknown. The objective of the current study was to provide a population-based description of ALL treatment patterns in AYA individuals over the past decade.Data regarding AYA patients aged 15 to 39 years and diagnosed with ALL between 2004 and 2014 while living in the Greater Bay Area were obtained from the Greater Bay Area Cancer Registry (GBACR). Treating facilities were designated as pediatric or adult centers; induction treatment regimens were abstracted from registry text data fields.Of 304 patients diagnosed in the GBACR catchment region, complete treatment data were available for 229 (75%). The location of care was identified for 296 patients (97%) treated at 31 unique centers. Approximately 70% of AYA patients received induction therapy at an adult treatment center. All AYA patients who were treated at pediatric centers received pediatric ALL regimens. Among AYA patients treated by adult oncologists with complete treatment data, none received a pediatric regimen before 2008. Between 2008 and 2012, while the US Adult Intergroup C10403 pediatric-inspired ALL protocol was open to accrual, 31% of AYA patients treated by adult oncologists received pediatric regimens. This rate fell to 21% from 2013 through 2014. Adult facilities treating ≥ 2 AYA patients with ALL per year captured in the GBACR were more likely to administer pediatric regimens than lower volume centers (P = .03).As of 2014, only a minority of AYA patients with ALL received pediatric ALL regimens at adult cancer centers. Cancer 2017;122-130. © 2016 American Cancer Society.

    View details for DOI 10.1002/cncr.30322

    View details for Web of Science ID 000394719100016

    View details for PubMedCentralID PMC5161602

  • Pharmacologic maintenance strategies following allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Leuk Lymphoma CJ, L., P, S., L, M. 2017; 58 (3): 516-527
  • Adoption of pediatric-inspired acute lymphoblastic leukemia regimens by adult oncologists treating adolescents and young adults: A population-based study. Cancer Muffly, L., Lichtensztajn, D., Shiraz, P., Abrahão, R., McNeer, J., Stock, W., Keegan, T., Gomez, S. L. 2016

    Abstract

    Studies have demonstrated superior outcomes for adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) who are treated using pediatric versus adult therapeutic regimens. To the best of our knowledge, whether adult oncologists in the United States have adopted this approach to ALL in AYA patients is currently unknown. The objective of the current study was to provide a population-based description of ALL treatment patterns in AYA individuals over the past decade.Data regarding AYA patients aged 15 to 39 years and diagnosed with ALL between 2004 and 2014 while living in the Greater Bay Area were obtained from the Greater Bay Area Cancer Registry (GBACR). Treating facilities were designated as pediatric or adult centers; induction treatment regimens were abstracted from registry text data fields.Of 304 patients diagnosed in the GBACR catchment region, complete treatment data were available for 229 (75%). The location of care was identified for 296 patients (97%) treated at 31 unique centers. Approximately 70% of AYA patients received induction therapy at an adult treatment center. All AYA patients who were treated at pediatric centers received pediatric ALL regimens. Among AYA patients treated by adult oncologists with complete treatment data, none received a pediatric regimen before 2008. Between 2008 and 2012, while the US Adult Intergroup C10403 pediatric-inspired ALL protocol was open to accrual, 31% of AYA patients treated by adult oncologists received pediatric regimens. This rate fell to 21% from 2013 through 2014. Adult facilities treating ≥ 2 AYA patients with ALL per year captured in the GBACR were more likely to administer pediatric regimens than lower volume centers (P = .03).As of 2014, only a minority of AYA patients with ALL received pediatric ALL regimens at adult cancer centers. Cancer 2017;122-130. © 2016 American Cancer Society.

    View details for DOI 10.1002/cncr.30322

    View details for PubMedID 27622953

  • Psychological morbidities in adolescent and young adult blood cancer patients during curative-intent therapy and early survivorship. Cancer Muffly, L. S., Hlubocky, F. J., Khan, N., Wroblewski, K., Breitenbach, K., Gomez, J., McNeer, J. L., Stock, W., Daugherty, C. K. 2016; 122 (6): 954-961

    Abstract

    Adolescents and young adults (AYAs) with cancer face unique psychosocial challenges. This pilot study was aimed at describing the prevalence of psychological morbidities among AYAs with hematologic malignancies during curative-intent therapy and early survivorship and at examining provider perceptions of psychological morbidities in their AYA patients.Patients aged 15 to 39 years with acute leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma who were undergoing curative-intent therapy (on-treatment group) or were in remission within 2 years of therapy completion (early survivors) underwent a semistructured interview that incorporated measures of anxiety, depression, and posttraumatic stress (PTS). A subset of providers (n = 15) concomitantly completed a survey for each of the first 30 patients enrolled that evaluated their perception of each subject's anxiety, depression, and PTS.Sixty-one of 77 eligible AYAs participated. The median age at diagnosis was 26 years (range, 15-39 years), 64% were male, and 59% were non-Hispanic white. On-treatment demographics differed significantly from early-survivor demographics only in the median time from diagnosis to interview. Among the 61 evaluable AYAs, 23% met the criteria for anxiety, 28% met the criteria for depression, and 13% met the criteria for PTS; 46% demonstrated PTS symptomatology. Thirty-nine percent were impaired in 1 or more psychological domains. Psychological impairments were as frequent among early survivors as AYAs on treatment. Provider perceptions did not significantly correlate with patient survey results.AYAs with hematologic malignancies experience substantial psychological morbidities while they are undergoing therapy and during early survivorship, with more than one-third of the patients included in this study meeting the criteria for anxiety, depression, or traumatic stress. This psychological burden may not be accurately identified by their oncology providers. Cancer 2015. © 2015 American Cancer Society.

    View details for DOI 10.1002/cncr.29868

    View details for PubMedID 26749023

  • The overlooked COST of multiple myeloma. The Lancet. Haematology de Souza, J. A., Muffly, L. 2015; 2 (10): e394-5

    View details for DOI 10.1016/S2352-3026(15)00192-1

    View details for PubMedID 26686034

  • Secondary solid cancer screening following hematopoietic cell transplantation. Bone marrow transplantation INAMOTO, Y., Shah, N. N., Savani, B. N., Shaw, B. E., Abraham, A. A., Ahmed, I. A., Akpek, G., Atsuta, Y., Baker, K. S., Basak, G. W., Bitan, M., DeFilipp, Z., GREGORY, T. K., Greinix, H. T., Hamadani, M., Hamilton, B. K., Hayashi, R. J., Jacobsohn, D. A., Kamble, R. T., Kasow, K. A., Khera, N., Lazarus, H. M., Malone, A. K., Lupo-Stanghellini, M. T., Margossian, S. P., Muffly, L. S., Norkin, M., Ramanathan, M., Salooja, N., Schoemans, H., Wingard, J. R., Wirk, B., Wood, W. A., Yong, A., Duncan, C. N., Flowers, M. E., Majhail, N. S. 2015; 50 (8): 1013-1023

    Abstract

    Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

    View details for DOI 10.1038/bmt.2015.63

    View details for PubMedID 25822223

    View details for PubMedCentralID PMC4989866

  • Patient Selection for Allogeneic Hematopoietic Cell Transplantation (HCT): the Evolution of HCT Risk Assessment. Current hematologic malignancy reports Muffly, L. 2015; 10 (1): 28-34

    Abstract

    The use of allogeneic hematopoietic cell transplantation is expanding, with disproportionate growth witnessed in older adults with hematologic malignancies. As the chronological age barrier to transplant fades, refining the pre-hematopoietic cell transplantation (HCT) risk assessment to better capture host health status and disease characteristics is essential. This review summarizes recent efforts to move the field forward towards achieving this goal. Many of these risk assessment tools are currently included in prospective clinical trials; routine clinical use requires greater understanding of how to best incorporate this new information into HCT decision making.

    View details for DOI 10.1007/s11899-014-0241-2

    View details for PubMedID 25500987

  • Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients HAEMATOLOGICA Muffly, L. S., Kocherginsky, M., Stock, W., Chu, Q., Bishop, M. R., Godley, L. A., Kline, J., Liu, H., Odenike, O. M., Larson, R. A., Van Besien, K., Artz, A. S. 2014; 99 (8): 1373-1379

    Abstract

    Allogeneic hematopoietic cell transplantation is increasingly utilized in older adults. This study prospectively evaluated the prognostic utility of geriatric assessment domains prior to allogeneic transplantation in recipients aged 50 years and over. Geriatric assessment was performed prior to transplant, and included validated measures across domains of function and disability, comorbidity, frailty, mental health, nutritional status, and systemic inflammation. A total of 203 patients completed geriatric assessment and underwent transplant. Median age was 58 years (range 50-73). After adjusting for established prognostic factors, limitations in instrumental activities of daily living (HR 2.38, 95%CI: 1.59-3.56; P<0.001), slow walk speed (HR 1.80, 95%CI: 1.14-2.83; P=0.01), high comorbidity by hematopoietic cell transplantation-specific comorbidity index (HR 1.56, 95%CI: 1.07-2.28; P=0.02), low mental health by short-form-36 mental component summary (HR 1.67, 95%CI: 1.13-2.48; P=0.01), and elevated serum C-reactive protein (HR 2.51, 95%CI: 1.54-4.09; P<0.001) were significantly associated with inferior overall survival. These associations were more pronounced in the cohort 60 years and over. Geriatric assessment measures confer independent prognostic utility in older allogeneic transplant recipients. Implementation of geriatric assessment prior to allogeneic transplantation may aid appropriate selection of older adults.

    View details for DOI 10.3324/haematol.2014.103655

    View details for Web of Science ID 000342834300022

    View details for PubMedID 24816237

  • Pilot Study of Comprehensive Geriatric Assessment (CGA) in Allogeneic Transplant: CGA Captures a High Prevalence of Vulnerabilities in Older Transplant Recipients BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Muffly, L. S., Boulukos, M., Swanson, K., Kocherginsky, M., del Cerro, P., Schroeder, L., Pape, L., Extermann, M., Van Besien, K., Artz, A. S. 2013; 19 (3): 429-434

    Abstract

    Comprehensive geriatric assessment (CGA) is frequently used in oncology to measure the health status of older adults with cancer, but it has not been studied in allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective pilot study of CGA in allogeneic HCT recipients aged ≥50 years to examine the prevalence of vulnerabilities in this population. Patients aged ≥50 years eligible for HCT were enrolled. CGA consisted mainly of self-reported, performance-based, and chart-extracted measures evaluating domains of comorbidity, physical and mental function, frailty, disability, and nutrition. Of 238 eligible patients, 166 completed CGA and underwent HCT. Only 1% had a Zubrod Performance Status score >1; 44% had high comorbidity defined by the Hematopoietic Cell Transplantation Comorbidity Index, and 66% had high comorbidity defined by the Cumulative Illness Rating Scale-Geriatrics. The presence of additional vulnerability was frequent. Disability was present in 40% by Instrumental Activities of Daily Living. Self-reported physical and mental function were significantly lower than population age group norms, 58% were pre-frail, and 25% were frail. Among those with Zubrod Performance Status score of 0, 28% demonstrated disability, 58% were pre-frail, 15% were frail, 35% reported low physical function, and 55% reported low mental function. CGA uncovers a substantial prevalence of undocumented impairments in functional status, frailty, disability, and mental health in older allogeneic HCT recipients.

    View details for DOI 10.1016/j.bbmt.2012.11.006

    View details for Web of Science ID 000315425700015

    View details for PubMedID 23160006

  • Microwave imaging for neoadjuvant chemotherapy monitoring: initial clinical experience BREAST CANCER RESEARCH Meaney, P. M., Kaufman, P. A., Muffly, L. S., Click, M., Poplack, S. P., Wells, W. A., Schwartz, G. N., di Florio-Alexander, R. M., Tosteson, T. D., Li, Z., Geimer, S. D., Fanning, M. W., Zhou, T., Epstein, N. R., Paulsen, K. D. 2013; 15 (2)

    Abstract

    Microwave tomography recovers images of tissue dielectric properties, which appear to be specific for breast cancer, with low-cost technology that does not present an exposure risk, suggesting the modality may be a good candidate for monitoring neoadjuvant chemotherapy.Eight patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer were imaged longitudinally five to eight times during the course of treatment. At the start of therapy, regions of interest (ROIs) were identified from contrast-enhanced magnetic resonance imaging studies. During subsequent microwave examinations, subjects were positioned with their breasts pendant in a coupling fluid and surrounded by an immersed antenna array. Microwave property values were extracted from the ROIs through an automated procedure and statistical analyses were performed to assess short term (30 days) and longer term (four to six months) dielectric property changes.Two patient cases (one complete and one partial response) are presented in detail and demonstrate changes in microwave properties commensurate with the degree of treatment response observed pathologically. Normalized mean conductivity in ROIs from patients with complete pathological responses was significantly different from that of partial responders (P value = 0.004). In addition, the normalized conductivity measure also correlated well with complete pathological response at 30 days (P value = 0.002).These preliminary findings suggest that both early and late conductivity property changes correlate well with overall treatment response to neoadjuvant therapy in locally advanced breast cancer. This result is consistent with earlier clinical outcomes that lesion conductivity is specific to differentiating breast cancer from benign lesions and normal tissue.

    View details for DOI 10.1186/bcr3418

    View details for Web of Science ID 000330612000018

    View details for PubMedID 23621959