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Umbilical Cord Transplant (UCBT) Without Serotherapy for Malignant and Non Malignant Diseases Provides a Curative Alternative with Improved Immune Reconstitution
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
POSTER SESSION I ALTERNATIVE DONORS
130 Umbilical Cord Transplant (UCBT) Without Serotherapy for Malignant and Non Malignant Diseases Provides a Curative Alternative with Improved Immune Reconstitution Paibel Ixia Aguayo-Hiraldo 1, Lisa Forbes 2, William Shearer 2, Jordan Orange 2, Swati Naik 3, Ghadir Sasa 3, Kathryn Leung 3, Stephen Gottschalk 3, Carl Allen 3, Nabil Ahmed 3, Malcolm K. Brenner 3, Ann M. Leen 4, Helen E. Heslop 3, Imelda C. Hanson 2, Robert A. Krance 3, Caridad Martinez 3. 1 Pediatric Hematology and Oncology, Stem Cell Transplant, Texas Children’s Hospital Cancer Center, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX; 2 Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX; 3 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX; 4 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston Methodist Hospital, Houston, TX UCBT is widely accepted as an alternative donor source in recent years but is associated with increased incidence of viral infection related mortality. In part this increased risk is due to delayed viral specific T cell function. In this prospective single center study we tested a novel conditioning regimen administering fludarabine and omitting lymphocytolytic antibodies such as ATG or Campath. 52 children, median age 8 months (1.5 mo-15 yr), underwent UCBT at our institution for both malignant and non-malignant disorders between 2009 and 2016. Indications for transplant: SCID (n = 25), HLH (n = 2), FA (n = 2), IPEX(n = 2), LAD(n = 1), WAS(n = 1), metabolic disorders (n = 3), DBA (n = 1), ALL(n = 5), AML(n = 3), JMML(n = 2), MDS(n = 4), and DC(n = 1). MAC conditioning therapy for non malignant and myeliod malignancy: Busulfan, Cyclophosphamide and Fludarabine: conditioning therapy for ALL: Cyclophosphamide, Fludarabine and TBI. Patients with chromosomal breakage/instability syndromes received a Reduced Intensity Regimen. Median time to neutrophil and platelet engraftment was 20.2 days; (range 8-35) and 45.7 days; (range 23159) respectively. 39/52 patients developed viral infections including 17 of them with recurence of infections diagnosed pre transplant. 14/17 pts with persistent viral infections preUCBT were able to clear the infection. Some of these patient’s virus specific response was evaluated using IFN-g ELISpot assay, with clearance of the infection associated with T cell recovery established at a median time of 35 days after UCBT (n = 8). The median CD3 absolute count was 326 x103(range 0-1314) and 506 (range 65-3693) at 42 and 60 days respectively. Median CD3+CD4+ was 264 (range .02-1077) and 381 (range 452620) for day 42 and 60 post UCBT, and C3+CD8+ median cell count was 57 (range .01-588) at 42 days and 89 (range 9-1195) at 60 days post. 42/52 patients are alive with a median follow up of 45 months (range 6- 89 months). The most common cause of death was relapse (5), complications of GvHD (2), and MOF secondary to bacterial septic shock (1). No patients died from viral disease. We conclude that, omitting lymphocytolytic antibodies from conditioning regimens for UCBT may be allow more rapid and effective T cell cellular and functional reconstitution without significant GvHD.
S119
131 Haploindentical Stem Cell Transplantation From Related Donors in Pediatric Patients Using a 2-Step Myeloablative Approach Sakshi Bami 1, Indira Sahdev 1, Rosemarie Corless 1, Susan Durham 1, Nan Werther 1, Patricia Shi 2, Rona Weinberg 2, Joel A. Brochstein 1. 1 Pediatric Hematology/ Oncology and Stem Cell Transplantation, Cohen Children’s Medical Center of New York, New Hyde Park, NY; 2 The New York Blood Center, New York, NY Background: Haploidentical hematopoietic stem cell transplant (HSCT) has expanded the pool of donors for patients who lack related or unrelated HLA matched donors. Grosso et al. (Biol Blood Marrow Transplant 21:646, 2015) used a 2-step myeloablative approach for haploidentical HSCT in adults, in which the lymphoid and myeloid portions of the graft were administered separately. This approach allows adjustments of the T-cell and CD34+ stem cell doses. Selective depletion of alloreactive T-cell clones is achieved by administering cyclophosphamide (CY) 3 days after donor lymphocyte infusion but before infusion of the CD34selected peripheral blood stem cell product, thereby avoiding stem cell exposure to CY. We report our initial experience with this 2-step approach in pediatric patients with hematologic malignancies. Methods: Between October 2015 and August 2016, 6 pediatric patients with hematologic malignancies underwent haploidentical stem cell transplantation. The median age at transplant was 9.6 years (range, 9.1-17.6 years). Two patients had myelodysplastic syndrome, 1 had initially refractory acute myeloid leukemia in complete remission (CR) 1 and 3 had ALL in CR 2. The father was the donor for 3 patients and the mother for the other 3. All patients received a conditioning regimen of total body irradiation (TBI) 1200 cGy and CY. Donor lymphocytes containing 2 × 108 CD3 cells/kg were infused immediately after the final TBI fraction, followed 66 hours later by administration of CY 60 mg/kg daily × 2. CD34+ selected donor peripheral blood stem cells were infused 2 days after the second CY dose. The median CD34+ cell dose was 5.7 × 106/kg (range, 4.1-9.9 × 106/kg). Tacrolimus and mycophenolate mofetil were used for GVHD prophylaxis. Results: Neutrophil engraftment and platelet engraftment (>20,000/uL) was seen in all patients at a median of 9.5 days (range, 9-10 days) and 13.5 days (range, 9-20 days) respectively. All patients achieved full donor chimerism with no secondary graft failure. Median length of stay was 25 days post-SCT (range, 18-43 days). Grade II acute GVHD was observed in 2 of 6 patients and grade III acute GVHD in 1 of 6 patients. All patients had a complete response to a short course of steroids. No acute GVHD was observed in 3 of 6 patients. One patient developed chronic GVHD limited to the skin. The median period of follow up was 148.5 days (range, 51-331 days). One patient (AML) relapsed at day +122 with multiple chloromas. Conclusion: Haploidentical SCT from related donors using this 2-step methodology is a feasible approach for pediatric patients with hematologic malignancies and results in an acceptable incidence of transient GVHD. Modifications to the conditioning regimen are planned in order to make this approach applicable to children with nonmalignant disorders.
POSTER SESSION I ALTERNATIVE DONORS
130 Umbilical Cord Transplant (UCBT) Without Serotherapy for Malignant and Non Malignant Diseases Provides a Curative Alternative with Improved Immune Reconstitution Paibel Ixia Aguayo-Hiraldo 1, Lisa Forbes 2, William Shearer 2, Jordan Orange 2, Swati Naik 3, Ghadir Sasa 3, Kathryn Leung 3, Stephen Gottschalk 3, Carl Allen 3, Nabil Ahmed 3, Malcolm K. Brenner 3, Ann M. Leen 4, Helen E. Heslop 3, Imelda C. Hanson 2, Robert A. Krance 3, Caridad Martinez 3. 1 Pediatric Hematology and Oncology, Stem Cell Transplant, Texas Children’s Hospital Cancer Center, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX; 2 Immunology, Allergy and Rheumatology, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX; 3 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX; 4 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston Methodist Hospital, Houston, TX UCBT is widely accepted as an alternative donor source in recent years but is associated with increased incidence of viral infection related mortality. In part this increased risk is due to delayed viral specific T cell function. In this prospective single center study we tested a novel conditioning regimen administering fludarabine and omitting lymphocytolytic antibodies such as ATG or Campath. 52 children, median age 8 months (1.5 mo-15 yr), underwent UCBT at our institution for both malignant and non-malignant disorders between 2009 and 2016. Indications for transplant: SCID (n = 25), HLH (n = 2), FA (n = 2), IPEX(n = 2), LAD(n = 1), WAS(n = 1), metabolic disorders (n = 3), DBA (n = 1), ALL(n = 5), AML(n = 3), JMML(n = 2), MDS(n = 4), and DC(n = 1). MAC conditioning therapy for non malignant and myeliod malignancy: Busulfan, Cyclophosphamide and Fludarabine: conditioning therapy for ALL: Cyclophosphamide, Fludarabine and TBI. Patients with chromosomal breakage/instability syndromes received a Reduced Intensity Regimen. Median time to neutrophil and platelet engraftment was 20.2 days; (range 8-35) and 45.7 days; (range 23159) respectively. 39/52 patients developed viral infections including 17 of them with recurence of infections diagnosed pre transplant. 14/17 pts with persistent viral infections preUCBT were able to clear the infection. Some of these patient’s virus specific response was evaluated using IFN-g ELISpot assay, with clearance of the infection associated with T cell recovery established at a median time of 35 days after UCBT (n = 8). The median CD3 absolute count was 326 x103(range 0-1314) and 506 (range 65-3693) at 42 and 60 days respectively. Median CD3+CD4+ was 264 (range .02-1077) and 381 (range 452620) for day 42 and 60 post UCBT, and C3+CD8+ median cell count was 57 (range .01-588) at 42 days and 89 (range 9-1195) at 60 days post. 42/52 patients are alive with a median follow up of 45 months (range 6- 89 months). The most common cause of death was relapse (5), complications of GvHD (2), and MOF secondary to bacterial septic shock (1). No patients died from viral disease. We conclude that, omitting lymphocytolytic antibodies from conditioning regimens for UCBT may be allow more rapid and effective T cell cellular and functional reconstitution without significant GvHD.
S119
131 Haploindentical Stem Cell Transplantation From Related Donors in Pediatric Patients Using a 2-Step Myeloablative Approach Sakshi Bami 1, Indira Sahdev 1, Rosemarie Corless 1, Susan Durham 1, Nan Werther 1, Patricia Shi 2, Rona Weinberg 2, Joel A. Brochstein 1. 1 Pediatric Hematology/ Oncology and Stem Cell Transplantation, Cohen Children’s Medical Center of New York, New Hyde Park, NY; 2 The New York Blood Center, New York, NY Background: Haploidentical hematopoietic stem cell transplant (HSCT) has expanded the pool of donors for patients who lack related or unrelated HLA matched donors. Grosso et al. (Biol Blood Marrow Transplant 21:646, 2015) used a 2-step myeloablative approach for haploidentical HSCT in adults, in which the lymphoid and myeloid portions of the graft were administered separately. This approach allows adjustments of the T-cell and CD34+ stem cell doses. Selective depletion of alloreactive T-cell clones is achieved by administering cyclophosphamide (CY) 3 days after donor lymphocyte infusion but before infusion of the CD34selected peripheral blood stem cell product, thereby avoiding stem cell exposure to CY. We report our initial experience with this 2-step approach in pediatric patients with hematologic malignancies. Methods: Between October 2015 and August 2016, 6 pediatric patients with hematologic malignancies underwent haploidentical stem cell transplantation. The median age at transplant was 9.6 years (range, 9.1-17.6 years). Two patients had myelodysplastic syndrome, 1 had initially refractory acute myeloid leukemia in complete remission (CR) 1 and 3 had ALL in CR 2. The father was the donor for 3 patients and the mother for the other 3. All patients received a conditioning regimen of total body irradiation (TBI) 1200 cGy and CY. Donor lymphocytes containing 2 × 108 CD3 cells/kg were infused immediately after the final TBI fraction, followed 66 hours later by administration of CY 60 mg/kg daily × 2. CD34+ selected donor peripheral blood stem cells were infused 2 days after the second CY dose. The median CD34+ cell dose was 5.7 × 106/kg (range, 4.1-9.9 × 106/kg). Tacrolimus and mycophenolate mofetil were used for GVHD prophylaxis. Results: Neutrophil engraftment and platelet engraftment (>20,000/uL) was seen in all patients at a median of 9.5 days (range, 9-10 days) and 13.5 days (range, 9-20 days) respectively. All patients achieved full donor chimerism with no secondary graft failure. Median length of stay was 25 days post-SCT (range, 18-43 days). Grade II acute GVHD was observed in 2 of 6 patients and grade III acute GVHD in 1 of 6 patients. All patients had a complete response to a short course of steroids. No acute GVHD was observed in 3 of 6 patients. One patient developed chronic GVHD limited to the skin. The median period of follow up was 148.5 days (range, 51-331 days). One patient (AML) relapsed at day +122 with multiple chloromas. Conclusion: Haploidentical SCT from related donors using this 2-step methodology is a feasible approach for pediatric patients with hematologic malignancies and results in an acceptable incidence of transient GVHD. Modifications to the conditioning regimen are planned in order to make this approach applicable to children with nonmalignant disorders.