Clinical Focus

  • Hematology
  • Leukemia
  • Medical Oncology

Academic Appointments

Professional Education

  • Board Certification: American Board of Internal Medicine, Hematology (2015)
  • Board Certification: American Board of Internal Medicine, Medical Oncology (2014)
  • Board Certification: American Board of Internal Medicine, Internal Medicine (2011)
  • Fellowship: UCSF Hematology and Medical Oncology Fellowship (2014) CA
  • Residency: UCSF Internal Medicine Residency (2011) CA
  • Medical Education: University of California Davis School of Medicine (2008) CA

Research & Scholarship

Clinical Trials

  • A Phase 1b Master Trial to Investigate CPX-351 in Subjects With Previously Untreated Acute Myeloid Leukemia Recruiting

    JZP025-101 is an open-label, multicenter, multi-arm, nonrandomized phase 1b master trial to determine the recommended phase 2 dose (RP2D) of CPX-351 when administered in combination with various targeted agents in previously untreated subjects with Acute Myeloid Leukemia (AML) who are fit to receive intensive chemotherapy (ICT). Subjects will be assigned to treatment arms based on results of AML mutation testing.

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  • Magrolimab Monotherapy or Magrolimab in Combination With Azacitidine in Patients With Hematological Malignancies Recruiting

    This trial will evaluate magrolimab, a monoclonal antibody which is designed to block a protein called CD47, which is widely expressed on human cancer cells. Blocking CD47 with magrolimab may enable the body's immune system to find and destroy the cancer cells. In this study, magrolimab may be given alone or in combination with azacitidine to patients with acute myeloid leukemia (AML) or higher risk myelodysplastic syndrome (MDS). Azacitidine is a drug used for treatment of AML or MDS in patients who are not eligible for typical chemotherapy. The major aims of the study are: to confirm the safety and tolerability of magrolimab monotherapy in a relapsed/refractory AML and MDS population, and of magrolimab in combination with azacitidine in previously untreated AML and MDS; to evaluate the efficacy of magrolimab monotherapy in relapsed/refractory AML/MDS, and of magrolimab in combination with azacitidine in previously untreated AML/MDS, as measured by the objective response rate; and to evaluate the safety, tolerability, and efficacy of magrolimab monotherapy or combination with azacitidine in low-risk MDS patients as measured by RBC transfusion independence rate.

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  • Study to Determine the Efficacy of Uproleselan (GMI-1271) in Combination With Chemotherapy to Treat Relapsed/Refractory Acute Myeloid Leukemia Recruiting

    This study will evaluate the efficacy of uproleselan (GMI-1271), a specific E-selectin antagonist, in combination with chemotherapy to treat relapsed/refractory AML, compared to chemotherapy alone. The safety of uproleselan when given with chemotherapy will also be investigated in patients with relapsed/refractory AML

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All Publications

  • Hypomethylating agents super-responders: challenging the dogma of long-term remission for acute myeloid leukemia. Annals of hematology Maakaron, J. E., Ozga, M. P., Mannis, G. N., Pulley, W., Foster, M. C., Zeidner, J. F., Mims, A. S. 2020

    View details for DOI 10.1007/s00277-020-04054-x

    View details for PubMedID 32377815

  • Improved Outcomes of Octogenarians and Nonagenarians with Acute Myeloid Leukemia in the Era of Novel Therapies. American journal of hematology Jeng, M. Y., Dutta, R., Tan, I. T., Zhang, T. Y., Mannis, G. N. 2020

    View details for DOI 10.1002/ajh.25949

    View details for PubMedID 32744731

  • Venetoclax and hypomethylating agent therapy in high risk myelodysplastic syndromes: a retrospective evaluation of a real-world experience. Leukemia & lymphoma Azizi, A., Ediriwickrema, A., Dutta, R., Patel, S. A., Shomali, W., Medeiros, B., Iberri, D., Gotlib, J., Mannis, G., Greenberg, P., Majeti, R., Zhang, T. 2020: 1?8


    Treatment with hypomethylating agents (HMAs) azacitidine or decitabine is the current standard of care for high risk myelodysplastic syndromes (MDSs) but is associated with low rates of response. The limited number of treatment options for patients with high risk MDS highlights a need for new therapeutic options. Venetoclax is an inhibitor of the BCL-2 protein which, when combined with an HMA, has shown high response rates in unfit and previously untreated acute myeloid leukemia. We performed a retrospective study of high risk MDS patients receiving combination HMA plus venetoclax in order to determine their effectiveness in this context. We show that in our cohort, the combination results in high response rates but is associated with a high frequency of myelosuppression. These data highlight the efficacy of combination HMA plus venetoclax in high risk MDS, warranting further prospective evaluation in clinical trials.

    View details for DOI 10.1080/10428194.2020.1775214

    View details for PubMedID 32543932

  • Maintenance Lenalidomide in Primary CNS Lymphoma. Annals of oncology : official journal of the European Society for Medical Oncology Rubenstein, J. L., Geng, H., Vu, K., Mannis, G., Formaker, P., Hwang, J., Munster, P. N., Damato, B. 2019

    View details for DOI 10.1093/annonc/mdz142

    View details for PubMedID 31046114

  • Limitation in Patient-Reported Function Is Associated with Inferior Survival in Older Adults Undergoing Autologous Hematopoietic Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Nawas, M. T., Andreadis, C., Martin, T. G., Wolf, J. L., Ai, W. Z., Kaplan, L. D., Mannis, G. N., Logan, A. C., Damon, L. E., Huang, C., Olin, R. L. 2019


    Although the use of geriatric assessment (GA) in the allogeneic hematopoietic cell transplantation (HCT) setting has been reported, few studies have evaluated the impact of patient-reported function on autologous HCT (autoHCT) outcomes. In this study, GA, including the administration of Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) quality of life tool, was performed in 184 patients age ?50 years (median age, 61 years; range, 50 to 75 years) before autoHCT. Associations among GA findings, quality of life metrics, and post-transplantation outcomes were evaluated using Cox regression. Indications for autoHCT included multiple myeloma (73%), non-Hodgkin lymphoma (20%), and other disorders (7%). The median progression-free survival (PFS) was 28 months, whereas the median overall survival (OS) was not reached. In unadjusted analysis, both PFS and OS were significantly associated with 5 GA components: limitation in instrumental activities of daily living, patient-reported Karnofsky Performance Status (KPS), and the Physical, Functional, and BMT subscale scores of the FACT-BMT. In multivariate analysis, 3 components-limitation in instrumental activities of daily living, patient-reported KPS, and FACT-BMT Physical subscale-remained predictive of both PFS and OS when adjusted for age, provider-reported KPS, disease status, and HCT comorbidity index. In older adults undergoing autoHCT, limitation in any 1 of 3 patient-reported measures of functional status was independently associated with inferior PFS and OS, even after adjusting for known prognostic factors.

    View details for DOI 10.1016/j.bbmt.2019.01.028

    View details for PubMedID 30708189

  • Allogeneic HSCT for adult-onset leukoencephalopathy with spheroids and pigmented glia. Brain : a journal of neurology Gelfand, J. M., Greenfield, A. L., Barkovich, M., Mendelsohn, B. A., Van Haren, K., Hess, C. P., Mannis, G. N. 2019


    Adult-onset leukoencephalopathy with spheroids and pigmented glia (ALSP) is an autosomal dominant leukoencephalopathy caused by mutations in colony stimulating factor 1 receptor (CSF1R). Here we report clinical and imaging outcomes following allogeneic haematopoietic stem cell transplantation (HSCT) in two patients with ALSP at the University of California, San Francisco between January 2016 and December 2017. Patient 1 proceeded to transplantation at age 53 with a haplo-identical sibling donor. Patient 2, whose sister and mother had died of the disease, proceeded to transplantation at age 49 with a 12/12 human leukocyte antigen-matched unrelated donor. Both patients received reduced intensity conditioning regimens. At 28 and 26 months post-HSCT, respectively, both patients were alive, without evidence of graft-versus-host disease, with major infection at 1 year in one and new-onset seizures in the other. In both cases, neurological worsening continued post-HSCT; however, the progression in cognitive deficits, overall functional status and gait impairment gradually stabilized. There was continued progression of parkinsonism in both patients. On brain MRI, within 1 year there was stabilization of T2/FLAIR abnormalities, and after 2 years there was complete resolution of abnormal multifocal reduced diffusion. In summary, after >2 years of follow-up, allogeneic HSCT in ALSP led to interval resolution of diffusion MRI abnormalities, stabilization of T2/FLAIR MRI abnormalities, and partial clinical stabilization, supportive of treatment response. Allogeneic HSCT may be beneficial in ALSP by providing a supply of bone marrow-derived brain-engrafting myeloid cells with donor wild-type CSF1R to repopulate the microglial niche.

    View details for DOI 10.1093/brain/awz390

    View details for PubMedID 31840744

  • Functional status as measured by geriatric assessment predicts inferior survival in older allogeneic hematopoietic cell transplant recipients. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Huang, L. W., Sheng, Y., Andreadis, C., Logan, A. C., Mannis, G. N., Smith, C. C., Gaensler, K. M., Martin, T. G., Damon, L. E., Steinman, M. A., Huang, C. Y., Olin, R. L. 2019


    Allogeneic hematopoietic cell transplantation (alloHCT) has been increasingly offered to older adults with hematologic malignancies. However, optimal methods to determine fitness for alloHCT have yet to be defined. We evaluated the ability of a comprehensive geriatric assessment (CGA) to predict post-alloHCT outcomes in a single-center prospective cohort study of patients aged 50 and older. Outcomes included overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM). A total of 148 patients were included, with median age 62 years (range 50-76). In multivariate regression analysis, several CGA measures of functional status were predictive of post-alloHCT outcomes, after adjusting for traditional prognostic factors. Any deficit in Instrumental Activities of Daily Living (IADL) was associated with inferior OS (hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.07-3.08, p=0.03) and PFS (HR 1.85, 95% CI 1.15-2.99, p=0.01). Medical Outcomes Study Physical Health scale (MOS-PH) score <85 was associated with inferior OS (HR 1.96, 95% CI 1.13-3.40, p=0.02), PFS (HR 1.75, 95% CI 1.07-2.88, p=0.03), and increased NRM (subdistribution HR 2.57, 95% CI 1.12-5.92, p=0.03). MOS-PH was also associated with the number of non-hematologic grade ?3 adverse events within the first 100 days after alloHCT (rate ratio 1.61, 95% CI 1.04-2.49, p=0.03). These findings support previous work suggesting that IADL is an important prognostic tool prior to alloHCT. MOS-PH is newly identified as an additional metric to identify older patients at higher risk of poor post-alloHCT outcomes, including toxicity and NRM.

    View details for DOI 10.1016/j.bbmt.2019.08.022

    View details for PubMedID 31493541

  • Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood Roboz, G. J., DiNardo, C. D., Stein, E. M., de Botton, S., Mims, A. S., Prince, G. T., Altman, J. K., Arellano, M. L., Donnellan, W., Erba, H. P., Mannis, G. N., Pollyea, D. A., Stein, A. S., Uy, G. L., Watts, J. M., Fathi, A. T., Kantarjian, H. M., Tallman, M. S., Choe, S., Dai, D., Fan, B., Wang, H., Zhang, V., Yen, K. E., Kapsalis, S. M., Hickman, D., Liu, H., Agresta, S. V., Wu, B., Attar, E. C., Stone, R. M. 2019


    Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (mIDH1) enzyme. From a phase 1 study of 258 patients with IDH1-mutant advanced hematologic malignancies, we report results for 34 patients with newly diagnosed acute myeloid leukemia (AML) ineligible for standard therapy who received ivosidenib 500 mg once daily. Median age was 76.5 years, 26 (76%) patients had secondary AML and 16 (47%) had received {greater than or equal to}1 hypomethylating agent for an antecedent hematologic disorder. The most common all-grade adverse events were diarrhea (n=18; 53%), fatigue (n=16; 47%), nausea (n=13; 38%), and decreased appetite (n=12; 35%). Differentiation syndrome was reported in 6 (18%) patients (grade {greater than or equal to}3 in 3 [9%]) and did not require treatment discontinuation. Complete remission (CR) + CR with partial hematologic recovery (CRh) rate was 42.4% (95% confidence interval [CI], 25.5-60.8%); CR rate was 30.3% (95% CI, 15.6-48.7%). Median durations of CR+CRh and CR were not reached, with 95% CI lower bounds of 4.6 and 4.2 months, respectively; 61.5% and 77.8% of patients remained in remission at 1 year. With median follow-up of 23.5 months (range, 0.6-40.9), median overall survival was 12.6 months (95% CI, 4.5-25.7). Of 21 (63.6%) patients who were transfusion dependent at baseline, 9 (42.9%) became transfusion independent. IDH1 mutation clearance was seen in 9/14 patients achieving CR+CRh (5/10 CR, 4/4 CRh). Ivosidenib monotherapy was well tolerated and induced durable remissions and transfusion independence in patients with newly diagnosed AML. (Trial registered at #NCT02074839.).

    View details for DOI 10.1182/blood.2019002140

    View details for PubMedID 31841594

  • Low-dose lenalidomide maintenance after induction therapy in older patients with primary central nervous system lymphoma. British journal of haematology Vu, K., Mannis, G., Hwang, J., Geng, H., Rubenstein, J. L. 2019

    View details for DOI 10.1111/bjh.15787

    View details for PubMedID 30714128

  • Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Tallman, M. S., Wang, E. S., Altman, J. K., Appelbaum, F. R., Bhatt, V. R., Bixby, D., Coutre, S. E., De Lima, M., Fathi, A. T., Fiorella, M., Foran, J. M., Hall, A. C., Jacoby, M., Lancet, J., LeBlanc, T. W., Mannis, G., Marcucci, G., Martin, M. G., Mims, A., O'Donnell, M. R., Olin, R., Peker, D., Perl, A., Pollyea, D. A., Pratz, K., Prebet, T., Ravandi, F., Shami, P. J., Stone, R. M., Strickland, S. A., Wieduwilt, M., Gregory, K. M., Hammond, L., Ogba, N. 2019; 17 (6): 721?49


    Acute myeloid leukemia (AML) is the most common form of acute leukemia among adults and accounts for the largest number of annual deaths due to leukemias in the United States. Recent advances have resulted in an expansion of treatment options for AML, especially concerning targeted therapies and low-intensity regimens. This portion of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML focuses on the management of AML and provides recommendations on the workup, diagnostic evaluation and treatment options for younger (age <60 years) and older (age ?60 years) adult patients.

    View details for DOI 10.6004/jnccn.2019.0028

    View details for PubMedID 31200351

  • Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML NEW ENGLAND JOURNAL OF MEDICINE DiNardo, C. D., Stein, E. M., de Botton, S., Roboz, G. J., Altman, J. K., Mims, A. S., Swords, R., Collins, R. H., Mannis, G. N., Pollyea, D. A., Donnellan, W., Fathi, A. T., Pigneux, A., Erba, H. P., Prince, G. T., Stein, A. S., Uy, G. L., Foran, J. M., Traer, E., Stuart, R. K., Arellano, M. L., Slack, J. L., Sekeres, M. A., Willekens, C., Choe, S., Wang, H., Zhang, V., Yen, K. E., Kapsalis, S. M., Yang, H., Dai, D., Fan, B., Goldwasser, M., Liu, H., Agresta, S., Wu, B., Attar, E. C., Tallman, M. S., Stone, R. M., Kantarjian, H. M. 2018; 378 (25): 2386?98


    Mutations in the gene encoding isocitrate dehydrogenase 1 ( IDH1) occur in 6 to 10% of patients with acute myeloid leukemia (AML). Ivosidenib (AG-120) is an oral, targeted, small-molecule inhibitor of mutant IDH1.We conducted a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated AML. Safety and efficacy were assessed in all treated patients. The primary efficacy population included patients with relapsed or refractory AML receiving 500 mg of ivosidenib daily with at least 6 months of follow-up.Overall, 258 patients received ivosidenib and had safety outcomes assessed. Among patients with relapsed or refractory AML (179 patients), treatment-related adverse events of grade 3 or higher that occurred in at least 3 patients were prolongation of the QT interval (in 7.8% of the patients), the IDH differentiation syndrome (in 3.9%), anemia (in 2.2%), thrombocytopenia or a decrease in the platelet count (in 3.4%), and leukocytosis (in 1.7%). In the primary efficacy population (125 patients), the rate of complete remission or complete remission with partial hematologic recovery was 30.4% (95% confidence interval [CI], 22.5 to 39.3), the rate of complete remission was 21.6% (95% CI, 14.7 to 29.8), and the overall response rate was 41.6% (95% CI, 32.9 to 50.8). The median durations of these responses were 8.2 months (95% CI, 5.5 to 12.0), 9.3 months (95% CI, 5.6 to 18.3), and 6.5 months (95% CI, 4.6 to 9.3), respectively. Transfusion independence was attained in 29 of 84 patients (35%), and patients who had a response had fewer infections and febrile neutropenia episodes than those who did not have a response. Among 34 patients who had a complete remission or complete remission with partial hematologic recovery, 7 (21%) had no residual detectable IDH1 mutations on digital polymerase-chain-reaction assay. No preexisting co-occurring single gene mutation predicted clinical response or resistance to treatment.In patients with advanced IDH1-mutated relapsed or refractory AML, ivosidenib at a dose of 500 mg daily was associated with a low frequency of grade 3 or higher treatment-related adverse events and with transfusion independence, durable remissions, and molecular remissions in some patients with complete remission. (Funded by Agios Pharmaceuticals; number, NCT02074839 .).

    View details for PubMedID 29860938

  • Venetoclax in Combination with Decitabine for Relapsed T-Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Cell Transplant CASE REPORTS IN HEMATOLOGY Rahmat, L. T., Nguyen, A., Abdulhaq, H., Prakash, S., Logan, A. C., Mannis, G. N. 2018: 6092646


    Long-term disease-free survival in adults with T-cell acute lymphoblastic leukemia (T-ALL) remains poor, particularly after relapse, with few available salvage options. Preclinical data suggest that inhibition of the antiapoptotic protein BCL-2 (B-cell lymphoma 2) either alone or in combination with other agents, may be a unique therapeutic approach for the treatment of T-ALL. We present a case of a young male with T-ALL, relapsed after allogeneic hematopoietic stem cell transplant, who achieved a second complete remission following salvage therapy with combined venetoclax and decitabine. Assessment of measurable residual disease by next generation sequencing showed no evidence of residual disease of a sensitivity of 1?×?10-6. While the combination of venetoclax and hypomethylating agents has shown promise in the treatment of relapsed/refractory AML, and to our knowledge, this is the first report of this combination demonstrating clinical activity in relapsed/refractory T-ALL.

    View details for DOI 10.1155/2018/6092646

    View details for Web of Science ID 000444206900001

    View details for PubMedID 30225152

    View details for PubMedCentralID PMC6129347

  • Discussion on reply to Foley et al., 'Acute myeloid leukemia with t(14;21) involving RUNX1 and SYNE2: A novel favorable-risk translocation?' CANCER GENETICS Mannis, G. N. 2018; 220: 77?78
  • Acute myeloid leukemia with t(14;21) involving RUNX1 and SYNE2: A novel favorable-risk translocation? CANCER GENETICS Foley, N., Van Ziffle, J., Yu, J., Qi, Z., Grenert, J. P., Yeh, I., Bastian, B., Kogan, S., Mannis, G. N. 2017; 216: 74?78


    In acute myeloid leukemia (AML), a translocation between chromosomes 8q22 and 21q22 leads to the RUNX1-RUNXT1 fusion gene which, in the absence of a concomitant KIT mutation, generally portends a more favorable prognosis. Translocations at 21q22, other than those involving 8q22, are uncommon, and the specific prognostic and therapeutic implications are accordingly limited by the small number of reported cases. In this report, we describe the case of a 67-year-old gentleman who presented with AML harboring t(14;21)(q23;q22). Subsequent molecular analysis revealed mutations in RUNX1, ASXL1, and SF3B1, with translocation breakpoints identified within SYNE2 on chromosome 14 and RUNX1 on chromosome 21. The functional consequence of the DNA fusion between SYNE2 and RUNX1 is unclear. Nonetheless, despite several adverse risk factors associated with this patient's AML, he achieved a long-lasting remission with standard chemotherapy alone, potentially suggestive of a novel favorable-risk translocation in AML involving 21q22.

    View details for DOI 10.1016/j.cancergen.2017.07.002

    View details for Web of Science ID 000414382900010

    View details for PubMedID 29025598

  • Advance care planning and end-of-life care for patients with hematologic malignancies who die after hematopoietic cell transplant. Bone marrow transplantation Eckhert, E. E., Schoenbeck, K. L., Galligan, D., McNey, L. M., Hwang, J., Mannis, G. N. 2017; 52 (6): 929?31

    View details for DOI 10.1038/bmt.2017.41

    View details for PubMedID 28287642

  • Regression of methotrexate-resistant AIDS-related primary central nervous system lymphoma with lenalidomide plus combination anti-retroviral therapy LEUKEMIA & LYMPHOMA Gupta, N. K., Wang, C., Mannis, G. N., Yu, J. J., Rubenstein, J. L. 2017; 58 (11): 2748?51

    View details for DOI 10.1080/10428194.2017.1312374

    View details for Web of Science ID 000406274600034

    View details for PubMedID 28395565

    View details for PubMedCentralID PMC6026016

  • Multigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Mule, M. P., Mannis, G. N., Wood, B. L., Radich, J. R., Hwang, J., Ramos, N. R., Andreadis, C., Damon, L., Logan, A. C., Martin, T. G., Hourigan, C. S. 2016; 22 (11): 1974?82


    We report here the largest study to date of adult patients with acute myeloid leukemia (AML) tested for measurable residual disease (MRD) at the time of autologous hematopoietic cell transplantation (auto-HCT). Seventy-two adult patients who underwent transplantation between 2004 and 2013 at a single academic medical center (University of California San Francisco) were eligible for this retrospective study based on availability of cryopreserved granulocyte colony-stimulating factor (GCSF)-mobilized autologous peripheral blood progenitor cell (PBPC) leukapheresis specimens ("autografts"). Autograft MRD was assessed by molecular methods (real-time quantitative PCR [RQ-PCR] for Wilms tumor 1 (WT1) alone or a multigene panel) and by multiparameter flow cytometry (MPFC). WT1 RQ-PCR testing of the autograft had low sensitivity for relapse prediction (14%) and a negative predictive value of 51%. MPFC failed to identify MRD in any of 34 autografts tested. Combinations of molecular MRD assays, however, improved prediction of post-auto-HCT relapse. In multivariate analysis of clinical variables, including age, gender, race, cytogenetic risk category, and CD34+ cell dose, only autograft multigene MRD as assessed by RQ-PCR was statistically significantly associated with relapse. One year after transplantation, only 28% patients with detectable autograft MRD were relapse free, compared with 67% in the MRD-negative cohort. Multigene MRD, while an improvement on other methods tested, was however suboptimal for relapse prediction in unselected patients, with specificity of 83% and sensitivity of 46%. In patients with known chromosomal abnormalities or mutations, however, better predictive value was observed with no relapses observed in MRD-negative patients in the first year after auto-HCT compared with 83% incidence of relapse in the MRD-positive patients (hazard ratio, 12.45; P?=?.0016). In summary, increased personalization of MRD monitoring by use of a multigene panel improved the ability to risk stratify patients for post-auto-HCT relapse. WT1 RQ-PCR and flow cytometric assessment for AML MRD in autograft samples had limited value for predicting relapse after auto-HCT. We demonstrate that cryopreserved autograft material presents unique challenges for AML MRD testing because of the masking effects of previous GCSF exposure on gene expression and flow cytometry signatures. In the absence of information regarding diagnostic characteristics, sources other than GCSF-stimulated PBSC leukapheresis specimens should be considered as alternatives for MRD testing in AML patients undergoing auto-HCT.

    View details for DOI 10.1016/j.bbmt.2016.08.014

    View details for Web of Science ID 000386544200010

    View details for PubMedID 27544285

    View details for PubMedCentralID PMC5072749

  • Paraproteinemic keratopathy as the presenting sign of hematologic malignancy AMERICAN JOURNAL OF HEMATOLOGY Mannis, T. E., Mannis, G. N., Waterhouse, E. G., Aldave, A. J., Rose-Nussbaumer, J. 2016; 91 (9): 961?62

    View details for DOI 10.1002/ajh.24327

    View details for Web of Science ID 000385237100167

    View details for PubMedID 26872417

    View details for PubMedCentralID PMC6038815

  • Quantification of Acute Lymphoblastic Leukemia Clonotypes in Leukapheresed Peripheral Blood Progenitor Cells Predicts Relapse Risk after Autologous Hematopoietic Stem Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Mannis, G. N., Martin, T. G., Damon, L. E., Andreadis, C., Olin, R. L., Kong, K. A., Faham, M., Hwang, J., Ai, W. Z., Gaensler, K. L., Sayre, P. H., Wolf, J. L., Logan, A. C. 2016; 22 (6): 1030?36


    Since the incorporation of tyrosine kinase inhibitors into the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), the notion that all patients with "high-risk" ALL uniformly require allogeneic (allo) hematopoietic cell transplantation (HCT) has received increasing scrutiny. Although multiple studies have shown superiority of alloHCT over autologous (auto) hematopoietic cell transplantation for high-risk patients, these findings may be explained, in part, by contamination of the peripheral blood progenitor cell (PBPC) leukapheresis product by residual leukemic cells in patients undergoing autoHCT. We retrospectively evaluated minimal residual disease (MRD) using next-generation sequencing (NGS) in the PBPC leukapheresis product of 32 ALL patients who underwent autoHCT. Twenty-eight patients (88%) had diagnostic samples with quantifiable immunoreceptor rearrangements to follow for MRD. Twelve (38%) patients had Ph+ B-ALL, 12 (38%) had Philadelphia chromosome-negative (Ph-) B-ALL, and 4 (14%) had T cell ALL. With a median follow-up of 41 months (range, 3 to 217), median relapse-free survival (RFS) and overall survival for the entire cohort were 3.2 and 4.2 years, respectively; at 5 years after transplantation, 42% of patients remain alive and relapse free. Using MRD detection at a threshold of ? 1 × 10(-6), median RFS for patients with detectable MRD was 6.5 months and was not reached for patients without detectable disease (P = .0005). In multivariate analysis, the only factor significantly associated with relapse was the presence of MRD ?1 × 10(-6) (odds ratio, 23.8; confidence interval, 1.8 to 312.9; P = .0158). Our findings suggest that NGS for MRD detection can predict long-term RFS in patients undergoing autoHCT for high-risk ALL.

    View details for DOI 10.1016/j.bbmt.2016.02.004

    View details for Web of Science ID 000376814000010

    View details for PubMedID 26899561

  • Inferior vena cava filter thrombosis CLINICAL CASE REPORTS Byrne, M., Mannis, G. N., Nair, J., Andreadis, C. 2016; 4 (2): 162?64


    Patients with inferior vena cava (IVC) filters - particularly permanent filters - are at increased risk for recurrent deep venous thrombosis (DVT). Judicious use of IVC filters, as well as the prompt retrieval of temporary IVC filters, substantially reduces the risk of IVC thrombosis.

    View details for DOI 10.1002/ccr3.418

    View details for Web of Science ID 000369149200015

    View details for PubMedID 26862415

    View details for PubMedCentralID PMC4736520

  • Long-term outcomes of patients with intermediate-risk acute myeloid leukemia treated with autologous hematopoietic cell transplant in first complete remission LEUKEMIA & LYMPHOMA Mannis, G. N., Martin, T. G., Damon, L. E., Logan, A. C., Olin, R. L., Flanders, M. D., Ai, W. Z., Gaensler, K. L., Kaplan, L. D., Sayre, P. H., Smith, C. C., Wolf, J. L., Andreadis, C. 2016; 57 (7): 1560?66


    In 2014, autologous hematopoietic cell transplant (autoHCT) was removed from the National Comprehensive Cancer Network guidelines as a recommended treatment for patients with intermediate-risk AML in first complete remission (CR1). We reviewed the outcomes of all patients with intermediate-risk AML treated with autoHCT in CR1 at our institution. Of 334 patients who underwent autoHCT for AML between 1988 and 2013, 133 patients with intermediate-risk AML in CR1 were identified. Cytogenetics were diploid in 97 (73%). With a median follow-up of 4.1 years (range 0.1-17), median overall survival (OS) is 6.7 years; at 5 years post-transplant, 59% of patients remain alive and 43% remain relapse-free. Forty-eight percent of relapsing patients proceeded to salvage alloHCT. Our findings demonstrate that nearly half of patients with intermediate-risk AML in CR1 achieve sustained remissions, and that salvage alloHCT is feasible in those who relapse. AutoHCT therefore remains a reasonable option for intermediate-risk patients with AML in CR1.

    View details for DOI 10.3109/10428194.2015.1088646

    View details for Web of Science ID 000377265000013

    View details for PubMedID 26490487

  • Long-term survival in AIDS-related primary central nervous system lymphoma. Neuro-oncology Gupta, N. K., Nolan, A., Omuro, A., Reid, E. G., Wang, C. C., Mannis, G., Jaglal, M., Chavez, J. C., Rubinstein, P. G., Griffin, A., Abrams, D. I., Hwang, J., Kaplan, L. D., Luce, J. A., Volberding, P., Treseler, P. A., Rubenstein, J. L. 2016


    The optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention.To identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX).We provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4 <100. This was confirmed in a multicenter analysis which demonstrated that integration of cART regimens with HD-MTX was generally well tolerated and resulted in longer progression-free survival than other treatments. No profound differences in immunophenotype were identified in an analysis of AR-PCNSL tumors that arose in the pre- versus post-cART eras. However, we detected evidence for a demographic shift, as the proportion of minority patients with AR-PCNSL increased since advent of cART.Long-term disease-free survival can be achieved in AR-PCNSL, even among those with histories of opportunistic infections, limited access to health care, and medical non-adherence. Given this, as well as the long-term toxicities of WBRT, we recommend that integration of cART plus first-line HD-MTX be considered for all patients with AR-PCNSL.

    View details for DOI 10.1093/neuonc/now155

    View details for PubMedID 27576871

  • The Transfusion Tether: Bridging the Gap Between End-Stage Hematologic Malignancies and Optimal End-of-Life Care. American journal of hematology Mannis, G. N., McNey, L. M., Gupta, N. K., Gross, D. M. 2016

    View details for PubMedID 26799788

  • A Phase I Study of Targeted, Dose-Escalated Intravenous Busulfan in Combination With Etoposide as Myeloablative Therapy for Autologous Stem Cell Transplantation in Acute Myeloid Leukemia CLINICAL LYMPHOMA MYELOMA & LEUKEMIA Mannis, G. N., Andreadis, C., Logan, A. C., Damon, L. E., Benet, L. Z., Ai, W. Z., Gaensler, K. L., Kaplan, L. D., Koplowicz, Y. B., Linker, C. A., Olin, R. L., Sayre, P. H., Smith, C. C., Sudhindra, A., Venstrom, J. M., Wolf, J. L., Martin, T. G. 2015; 15 (6): 377?83


    Busulfan and etoposide have been used as myeloablative therapy for autologous hematopoietic stem cell transplantation (HSCT) in adults with acute myeloid leukemia (AML) for > 20 years. The use of targeted intravenous (I.V.) busulfan has significantly improved the tolerability and efficacy of this regimen. We designed a dose-escalation study to examine the maximum tolerated dose (MTD) of targeted I.V. busulfan with bolus etoposide as preparative therapy for autologous HSCT in AML.In this single-center, phase I study, adult AML patients received I.V. busulfan targeted to either an area under the curve (AUC) of 1250 (cohort 1) or 1400 (cohort 2) ?mol/min over 16 doses. Dose adjustments based on plasma pharmacokinetics occurred before doses 2 and 11. Etoposide 60 mg/kg I.V. was administered 24 hours after the last busulfan dose and 3 days before stem cell infusion.Twelve patients with intermediate-risk AML in first complete remission were treated. All patients in cohort 1 and 5 patients (83%) in cohort 2 were within 10% of the target AUC. The MTD was not reached, although Grade ? 3 mucositis occurred in 3 patients (50%) in cohort 1 and in 4 patients (66%) in cohort 2, limiting further dose escalation. Two-year relapse-free survival was 33% in cohort 1 versus 67% in cohort 2 (P = .08).Etoposide and targeted, dose-escalated I.V. busulfan as myeloablative therapy for autologous HSCT in AML is safe, with mucositis being the most significant toxicity. A phase II study is warranted to further evaluate the activity and safety of busulfan targeted to AUC 1400 ?mol/min.

    View details for DOI 10.1016/j.clml.2015.02.016

    View details for Web of Science ID 000356397700010

    View details for PubMedID 25776193

  • Delayed hematopoietic recovery after auto-SCT in patients receiving arsenic trioxide-based therapy for acute promyelocytic leukemia: a multi-center analysis BONE MARROW TRANSPLANTATION Mannis, G. N., Logan, A. C., Leavitt, A. D., Yanada, M., Hwang, J., Olin, R. L., Damon, L. E., Andreadis, C., Ai, W. Z., Gaensler, K. M., Greene, C. C., Gupta, N. K., Kaplan, L. D., MAHINDRA, A., Miyazaki, Y., Naoe, T., Ohtake, S., Sayre, P. H., Smith, C. C., Venstrom, J. M., Wolf, J. L., Caballero, L., Emi, N., Martin, T. G. 2015; 50 (1): 40-44


    A potential link between arsenic (ATO)-based therapy and delayed hematopoietic recovery after autologous hematopoietic SCT (HSCT) for acute promyelocytic leukemia (APL) has previously been reported. We retrospectively reviewed the clinical histories of 58 patients undergoing autologous HSCT for APL at 21 institutions in the United States and Japan. Thirty-three (56%) of the patients received ATO-based therapy prior to stem cell collection. Delayed neutrophil engraftment occurred in 10 patients (17%): 9 of the 10 patients (90%) received prior ATO (representing 27% of all ATO-treated patients), compared with 1 of the 10 patients (10%) not previously treated with ATO (representing 4% of all ATO-naïve patients; P<0.001). Compared with ATO-naïve patients, ATO-treated patients experienced significantly longer times to ANC recovery (median 12 days vs 9 days, P<0.001). In multivariate analysis, the only significant independent predictor of delayed neutrophil engraftment was prior treatment with ATO (hazard ratio 4.87; P<0.001). Of the available stem cell aliquots from APL patients, the median viable post-thaw CD34+ cell recovery was significantly lower than that of cryopreserved autologous stem cell products from patients with non-APL AML. Our findings suggest that ATO exposure prior to CD34+ cell harvest has deleterious effects on hematopoietic recovery after autologous HSCT.

    View details for DOI 10.1038/bmt.2014.201

    View details for Web of Science ID 000347806800008

    View details for PubMedID 25243620

  • Ibrutinib rash in a patient with 17p del chronic lymphocytic leukemia. American journal of hematology Mannis, G., Wu, D., Dea, T., Mauro, T., Hsu, G. 2015; 90 (2): 179

    View details for DOI 10.1002/ajh.23775

    View details for PubMedID 24890909

    View details for PubMedCentralID PMC4548957

  • How I treat CNS lymphomas BLOOD Rubenstein, J. L., Gupta, N. K., Mannis, G. N., LaMarre, A. K., Treseler, P. 2013; 122 (14): 2318-2330


    The pathogenesis of primary and secondary central nervous system (CNS) lymphoma poses a unique set of diagnostic, prognostic, and therapeutic challenges. During the past 10 years, there has been significant progress in the elucidation of the molecular properties of CNS lymphomas and their microenvironment, as well as evolution in the development of novel treatment strategies. Although a CNS lymphoma diagnosis was once assumed to be uniformly associated with a dismal prognosis, it is now reasonable to anticipate long-term survival, and possibly a cure, for a significant fraction of CNS lymphoma patients. The pathogenesis of CNS lymphomas affects multiple compartments within the neuroaxis, and proper treatment of the CNS lymphoma patient requires a multidisciplinary team with expertise not only in hematology/oncology but also in neurology, neuroradiology, neurosurgery, clinical neuropsychology, ophthalmology, pathology, and radiation oncology. Given the evolving principles of management and the evidence for improvements in survival, our goal is to provide an overview of current knowledge regarding the pathogenesis of CNS lymphomas and to highlight promising strategies that we believe to be most effective in establishing diagnosis, staging, and therapeutic management.

    View details for DOI 10.1182/blood-2013-06-453084

    View details for Web of Science ID 000326078200015

    View details for PubMedID 23963042

    View details for PubMedCentralID PMC3790503

  • Risk-Reducing Salpingo-oophorectomy and Ovarian Cancer Screening in 1077 Women After BRCA Testing JAMA INTERNAL MEDICINE Mannis, G. N., Fehniger, J. E., Creasman, J. S., Jacoby, V. L., Beattie, M. S. 2013; 173 (2): 96?103


    For women at potentially increased risk for ovarian cancer, data regarding screening and risk reduction are limited. Previous studies have reported on the behaviors of BRCA mutation carriers, but less is known about the behaviors of non- BRCA carriers. We surveyed a large cohort of women after BRCA testing to identify the prevalence and posttest predictors of risk-reducing and screening interventions.A median of 3.7 years after BRCA testing, 1447 women who received genetic counseling and BRCA testing at 2 hospital sites were surveyed, with a 77.6% response rate. We analyzed data from 1077 survey respondents. We performed univariate and multivariate logistic regression analyses to identify predictors of risk-reducing salpingo-oophorectomy (RRSO), screening transvaginal ultrasonography (TVUS), and screening serum cancer antigen 125 (CA-125).Among the respondents, 201 women (18.7%) received positive test results for a deleterious mutation, 103 women (9.6%) received true-negative results, and 773 women (71.8%) received uninformative results. Overall, 19.1% of eligible women underwent RRSO and 39.6% used screening procedures. A positive BRCA result predicted RRSO (odds ratio [OR], 28.1; 95% CI, 16.2-48.6), TVUS (9.5 [4.3-21.0]), and serum CA-125 (13.0 [5.5-29.0]). Similarly, a true-negative BRCA result reduced the OR for RRSO (0.1 [0.0-0.6]), TVUS (0.2 [0.1-0.5]), and serum CA-125 (0.3 [0.1-0.7]). Of the 71.8% of women who received uninformative results after BRCA testing, 12.3% subsequently underwent RRSO, 33.8% reported ever having undergone screening serum CA-125 since BRCA testing, and 37.3% reported ever having undergone screening TVUS since BRCA testing.Results of BRCA testing strongly predict RRSO and ovarian cancer screening. Use of RRSO and ovarian screening was reported in a sizable percentage of non- BRCA carriers despite insufficient data to determine the effectiveness of these interventions.

    View details for DOI 10.1001/2013.jamainternmed.962

    View details for Web of Science ID 000317239700004

    View details for PubMedID 23247828

    View details for PubMedCentralID PMC4989513

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