Unrelated Donor Peripheral Stem Cell Research Articles

17 - Unrelated Donor Peripheral Stem Cell Transplantation (SCT) with Ex Vivo T Cell Receptor (TCR) αβ+/CD19+depletion for Pediatric Patients with Bone Marrow Failure (BMF)

17 - Unrelated Donor Peripheral Stem Cell Transplantation (SCT) with Ex Vivo T Cell Receptor (TCR) αβ+/CD19+depletion for Pediatric Patients with Bone Marrow Failure (BMF)

601 - Two Partial T Cell Depletion Strategies for Unrelated Donor Peripheral Stem Cell Transplantation are Associated with Excellent Outcomes for Pediatric Patients with Bone Marrow Failure (BMF)

601 - Two Partial T Cell Depletion Strategies for Unrelated Donor Peripheral Stem Cell Transplantation are Associated with Excellent Outcomes for Pediatric Patients with Bone Marrow Failure (BMF)

OR37 Persistence of T cells from the first donor after a second allogeneic stem cell transplantation

The monitoring of chimerism is a standard procedure to help assess engraftment and achievement of full donor lymphoid cells after allogeneic stem cell transplantation. T cell chimerism analysis is essential since T cells support the engraftment of hematopoietic stem cells and progenitor cells. TCRαβ T cells provide anti-tumor activity but can also cause graft vs. host disease (GVHD). In contrast, TCRγδ T cells have been found not to be associated with GVHD. Here we report a case in which residual T cells from the first donor were identified in a patient who received a second conditioning regiment and a subsequent second hematopoietic stem cell transplant. These cells from the first donor need to be closely monitored since they are TCRαβ T cells. A 10-year old male with high risk Acute Myeloid Leukemia received a 10/10 matched unrelated donor peripheral stem cell transplant (PSCT) with TCRαβ T cell depletion in May of 2015. He had been doing well until July 2016 when he relapsed. The patient underwent one dose of donor lymphocyte infusion in August 2016, with no improvement. He then received the second conditioning regimen and a KIR favorable maternal haplo-identical CD3/CD19 depleted PSCT on 11/9/16. The patient has done well overall post-transplant. He remains in remission with 100% donor engraftment without GVHD. Interestingly, his T cell engraftment analysis indicates he has T cell chimerism. 9% of his T cells are from the first unrelated donor and 91% are from the second donor. A subsequent analysis of TCRγδ T cell enriched engraftment showed that 100% of the TCRγδ T cells were from the second donor. This result suggests that the residual T cells identified from the first donor were most likely TCRαβ T cells. These results demonstrated that even after TCRαβ-depletion of the first graft and intensified immunosuppressive therapy conditioning regiment prior to the second transplant, CD3 + TCRαβ T cells from the first donor persisted. The patient is currently in remission. The expansion of the first donor T cells would strongly suggest a high risk of GVHD. Thus, it is clinically relevant to closely monitor these cells.

P141 Mirage syndrome with bone marrow stem cell transplant: A case report

MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes and enteropathy) syndrome is a recently described multisystem disorder that is related to gain of function of the growth repressor SAMD9. Due to the dominant suppressive effect of SAMD9 mutants, MIRAGE syndrome is associated with high mortality. A new publication this year suggests bone marrow transplantation (BMT) may be necessary for survival. Here we report a case of a patient who developed unexpected post-transplant complication and raise concerns of BMT as a treatment for the MIRAGE syndrome patients. A 23-month female with a history of congenital amegakaryocytic thrombocytopenia appears associated with MIRAGE syndrome, received a 9/10 matched (one mismatch at C locus) unrelated donor peripheral stem cell transplant in April of 2016. Although the patient has fully engrafted, her graft did not function properly. She had hemolytic anemia, marked decreased granulopoiesis in the marrow and persistent neutropenia, which further resulted in several episodes of sepsis. The underneath etiology is likely autoimmune related reactivity. Further tests excluded HLA antibody mediated response. Instead an alloreactive clonal T cell population was found in her bone marrow, which was consistent with the clinical observation that her neutrophil counts were improved to normal level after the T-cell-targeted chemotherapy. However, the patient passed away 10 months post-transplant due to respiratory failure. The patient was identified to have features of thymic hypoplasia, atrophic ovaries and bilateral adrenal hypoplasia that is consistent with the MIRAGE syndrome diagnosis. Moreover, the histology of the patient’s hypoplasia thymus showed lymphocyte depletion, lacking of corticomedullary demarcation, absence of Hassall’s corpuscles and extensive adipocytic infiltration. These results suggest the patient’s thymus is defective in supporting T cell development, and the development of the alloreactive T cells that targeted specifically her neutrophil is most likely due to a disfunction of her thymus. Since thymic hypoplasia is one of the features of MIGRAGE syndrome, this case suggests bone marrow transplant might not be the primary choice of the treatment for MIRAGE syndrome patient.

Impact of postremission consolidation chemotherapy on outcome after reduced‐intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete remission: A report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

BACKGROUNDThe objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced‐intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1).METHODSOf the 789 consecutive patients with AML in CR1 who underwent RIC alloSCT from a human leukocyte antigen‐matched sibling or matched unrelated donor peripheral stem cell grafts between 2001 and 2010, 591 patients received at least 1 cycle of consolidation chemotherapy and 198 patients did not receive any consolidation chemotherapy before alloSCT. To minimize inherent survival bias in favor of patients who underwent transplant long after achieving CR1, the study focused on 373 patients who underwent transplant within the median time frame between achievement of CR1 and alloSCT (3 months for patients who underwent alloSCT from matched siblings and 4 months for patients who underwent alloSCT from matched unrelated donors). In this subgroup, 151 patients did not receive any consolidation chemotherapy and 222 patients received ≥ 1 consolidation chemotherapy cycle.RESULTSWith a median follow‐up of 36 months (range, 2 months‐135 months), the 3‐year cumulative recurrence incidence (RI) was not significantly different between the groups (36% ± 4% for the group treated without consolidation chemotherapy vs 38% ± 3% for patients who received consolidation chemotherapy; P = .89). In addition, leukemia‐free survival was similar between the groups (45% ± 4% and 47% ± 3%, respectively; P = .41). Dose intensity of cytarabine given during consolidation chemotherapy appeared to have no influence on RI. On multivariate analysis, pretransplant consolidation (≥ 1 cycle vs 0 cycles) was found to have no significant impact on RI (hazards ratio, 1.29; 95% confidence interval, 0.84‐1.97 [P = .24]) or leukemia‐free survival (hazards ratio, 1.00; 95% confidence interval, 0.71‐1.42 [P = .99]).CONCLUSIONSThe data from the current study suggest no apparent advantage for postremission consolidation chemotherapy before RIC alloSCT, provided a donor is readily available. Cancer 2014;120:855–863. © 2013 American Cancer Society.