Khoa Thomas Pham

All Publications

• Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal. Science translational medicine Busque, S., Scandling, J. D., Lowsky, R., Shizuru, J., Jensen, K., Waters, J., Wu, H. H., Sheehan, K., Shori, A., Choi, O., Pham, T., Fernandez Vina, M. A., Hoppe, R., Tamaresis, J., Lavori, P., Engleman, E. G., Meyer, E., Strober, S. 2020; 12 (528)

  Abstract

  Preclinical studies have shown that persistent mixed chimerism is linked to acceptance of organ allografts without immunosuppressive (IS) drugs. Mixed chimerism refers to continued mixing of donor and recipient hematopoietic cells in recipient tissues after transplantation of donor cells. To determine whether persistent mixed chimerism and tolerance can be established in patients undergoing living donor kidney transplantation, we infused allograft recipients with donor T cells and hematopoietic progenitors after posttransplant lymphoid irradiation. In 24 of 29 fully human leukocyte antigen (HLA)-matched patients who had persistent mixed chimerism for at least 6 months, complete IS drug withdrawal was achieved without subsequent evidence of rejection for at least 2 years. In 10 of 22 HLA haplotype-matched patients with persistent mixed chimerism for at least 12 months, reduction of IS drugs to tacrolimus monotherapy was achieved. Withdrawal of tacrolimus during the second year resulted in loss of detectable chimerism and subsequent rejection episodes, unless tacrolimus therapy was reinstituted. Posttransplant immune reconstitution of naïve B cells and B cell precursors was more rapid than the reconstitution of naïve T cells and thymic T cell precursors. Robust chimerism was observed only among naïve T and B cells but not among memory T cells. No evidence of rejection was observed in all surveillance graft biopsies obtained from mixed chimeric patients withdrawn from IS drugs, and none developed graft-versus-host disease. In conclusion, persistent mixed chimerism established in fully HLA- or haplotype-matched patients allowed for complete or partial IS drug withdrawal without rejection.

  View details for DOI 10.1126/scitranslmed.aax8863

  View details for PubMedID 31996467

• Kidney transplant outcomes and function following simultaneous heart kidney transplant compared to solitary kidney transplant from the same donor Than, P., Brubaker, A., Taiwo, A., Pham, T. WILEY. 2020: 89

  View details for Web of Science ID 000505634300187

• Are two operations better than one? The debate over combined versus sequential liver-kidney transplantation from a single live donor in the treatment of primary hyperoxaluria 1 PEDIATRIC TRANSPLANTATION Pham, T. A., Esquivel, C. 2019; 23 (4)

  View details for DOI 10.1111/petr.13457

  View details for Web of Science ID 000470844700016

• Are two operations better than one? The debate over combined versus sequential liver-kidney transplantation from a single live donor in the treatment of primary hyperoxaluria 1. Pediatric transplantation Pham, T. A., Esquivel, C. 2019: e13457

  View details for PubMedID 31081215

• Living Kidney Donation: Strategies to Increase the Donor Pool. The Surgical clinics of North America Lee, L., Pham, T. A., Melcher, M. L. 2019; 99 (1): 37–47

  Abstract

  End-stage renal disease (ESRD) is a significant health care burden. Although kidney transplantation is the optimal treatment modality, less than 25% of waiting list patients are transplanted because of organ shortage. Living kidney donation can lead to better recipient and graft survival and increase the number of donors. Not all ESRD patients have potential living donors, and not all living donors are a compatible match to recipients. Kidney paired exchanges allow incompatible pairs to identify compatible living donors for living donor kidney transplants for multiple recipients. Innovative modifications of kidney paired donation can increase the number of kidney transplants, with excellent outcomes.

  View details for PubMedID 30471740

• Living Kidney Donation: Strategies to Increase the Donor Pool SURGICAL CLINICS OF NORTH AMERICA Lee, L., Pham, T. A., Melcher, M. L. 2019; 99 (1): 37-+

  View details for DOI 10.1016/j.suc.2018.09.003

  View details for Web of Science ID 000454664200003

• Socioeconomic Status in Non-directed and Voucher-based Living Kidney Donation EUROPEAN UROLOGY FOCUS Nassiri, N., Baskin, A. S., Herbert, L. K., Connor, S., Pham, T., Melcher, M. L., Sinacore, J., Veale, J. L. 2018; 4 (2): 185–89

  View details for DOI 10.1016/j.euf.2018.07.020

  View details for Web of Science ID 000486143800011

• Socioeconomic Status in Non-directed and Voucher-based Living Kidney Donation. European urology focus Nassiri, N., Baskin, A. S., Herbert, L. K., Connor, S., Pham, T., Melcher, M. L., Sinacore, J., Veale, J. L. 2018; 4 (2): 185–89

  Abstract

  BACKGROUND: Little has been reported about the socioeconomic status (SES) and demographics of non-directed (altruistic) and voucher-based donation.OBJECTIVE: To analyze common characteristics amongst altruistic donors in order to promote non-directed and voucher-based donation.DESIGN, SETTING, AND PARTICIPANTS: Information regarding altruistic donations from 2008 to 2015 and voucher-based donors was obtained from the National Kidney Registry.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: An SES index, created and validated by the Agency for Healthcare Research and Quality (AHRQ), was created by geocoding the donor's zip code and linking it to seven publicly available SES variables found in the 2010 United States Census data.RESULTS AND LIMITATIONS: In total, 267 non-directed and 3 voucher-based donations were identified. Non-directed donors were predominantly female (58%), with an average age of 45.6 yr (range, 21-72). The mean SES index score was 55.6 (SD=3.2), which corresponds to the 77th percentile of 1.5 million MediCare beneficiaries as reported by the AHRQ in 2008. Voucher-based donors were Caucasian males of high SES. The study was limited by the number of voucher-based donations.CONCLUSIONS: Non-directed and voucher-based donors are in the upper end of the economic spectrum. The voucher-based program has built within it the inherent capacity to remove disincentives to donation, which currently limit altruistic donation.PATIENT SUMMARY: We wanted to determine what types of people donated their kidneys altruistically, so that we could understand how to motivate more people to donate their kidneys. The voucher-based program was recently started and is a promising tool to motivate many people to donate kidneys by removing major disincentives to donation.

  View details for PubMedID 30122635

• Kidney paired exchange and desensitization: Strategies to transplant the difficult to match kidney patients with living donors TRANSPLANTATION REVIEWS Pham, T. A., Lee, J. I., Melcher, M. L. 2017; 31 (1): 29-34

  Abstract

  With organs in short supply, only a limited number of kidney transplants can be performed a year. Live donor donation accounts for 1/3rd of all kidney transplants performed in the United States. Unfortunately, not every donor recipient pair is feasible because of Human leukocyte antigen (HLA) sensitization and ABO incompatibility. To overcome these barriers to transplant, strategies such as kidney paired donation (KPD) and desensitization have been developed. KPD is the exchange of donors between at least two incompatible donor-recipient pairs such that they are now compatible. Desensitization is the removal of circulating donor specific antibodies to prevent graft rejection. Regardless of the treatment strategy, highly sensitized patients whose calculated panel reactive antibody (cPRA) is ≥95% remain difficult to transplant with match rates as low as 15% in KPD pools. Desensitization has proved to be difficult in those with high antibody titers. A novel approach is the combination of both KPD and desensitization to facilitate compatible and successful transplantation. A highly sensitized patient can be paired with a better immunological match in the KPD pool and subsequently desensitized to a lesser degree. This article reviews the current progress in KPD and desensitization and their use as a combined therapy.

  View details for DOI 10.1016/j.trre.2017.01.003

  View details for PubMedID 28284304

• Living donor liver transplantation for inborn errors of metabolism - An underutilized resource in the United States. Pediatric transplantation Pham, T. A., Enns, G. M., Esquivel, C. O. 2016; 20 (6): 770-773

  Abstract

  Inborn metabolic diseases of the liver can be life-threatening disorders that cause debilitating and permanent neurological damage. Symptoms may manifest as early as the neonatal period. Liver transplant replaces the enzymatically deficient liver, allowing for metabolism of toxic metabolites. LDLT for metabolic disorders is rarely performed in the United States as compared to countries such as Japan, where they report >2000 cases performed within the past two decades. Patient and graft survival is comparable to that of the United States, where most of the studies are based on deceased donors. No living donor complications were observed, suggesting that LDLT is as safe and effective as deceased donor transplants performed in the USA. Increased utilization of living donors in the USA will allow for early transplantation to prevent permanent neurological damage in those with severe disease. Pediatric transplant centers should consider utilizing living donors when feasible for children with metabolic disorders of the liver.

  View details for DOI 10.1111/petr.12746

  View details for PubMedID 27392539

• Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer JAMA SURGERY Pham, T. A., Gallo, A. M., Concepcion, W., Esquivel, C. O., Bonham, C. A. 2015; 150 (12): 1150-1158

  Abstract

  Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed.To determine the efficacy of liver transplant in children with HBL or HCC.This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria.Disease-free and overall patient survival and graft survival.Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence.Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.

  View details for DOI 10.1001/jamasurg.2015.1847

  View details for Web of Science ID 000367990700010

• Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer. JAMA surgery Pham, T. A., Gallo, A. M., Concepcion, W., Esquivel, C. O., Bonham, C. A. 2015; 150 (12): 1150–58

  Abstract

  Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed.To determine the efficacy of liver transplant in children with HBL or HCC.This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria.Disease-free and overall patient survival and graft survival.Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence.Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.

  View details for PubMedID 26308249

• Demographic and Clinical Characteristics of 207 Non-Directed Donors Participating in Paired Exchange Through the National Kidney Registry Pham, T., Waterman, A., Veale, J., Melcher, M. WILEY-BLACKWELL. 2015: 79

  View details for Web of Science ID 000348030600090