Successful Haploidentical Stem Cell Transplant With Posttransplant Cyclophosphamide in Wiskott-Aldrich Syndrome With Myeloablative Conditioning.

Hematopoietic stem cell transplant (HSCT) is the only curative treatment modality for Wiskott-Aldrich syndrome. Haploidentical HSCT with posttransplant cyclophosphamide (PTCy) is an upcoming option in children with nonmalignant conditions. However, only few cases have been reported for Wiskott-Aldrich syndrome HSCT with PTCy approach. Here we report a 4-year-old boy, treated successfully by haploidentical HSCT with myeloablative conditioning (busulfan, fludarabine, and thiotepa) and PTCy. Posttransplant chimerism was fully donor. Of 13 cases (current case and other 12 published cases) 10 are alive and disease free after haploidentical HSCT with PTCy. Haploidentical HSCT with PTCy using myeloablative conditioning is feasible and safe.

Sharma A ，Rastogi N ，Kapoor R ，Chatterjee G ，Yadav SP ... -  《-》

Posttransplant cyclophosphamide for haploidentical stem cell transplantation in children with Wiskott-Aldrich syndrome.

Hematopoietic stem cell transplantation (HSCT) is the curative treatment for Wiskott-Aldrich syndrome (WAS). However, it is difficult to find a matched donor for patients. Therefore, haploidentical donors should be considered for patients lacking a suitable donor. Our pilot study evaluated whether HSCT with posttransplantation cyclophosphamide (PTCy) is an effective treatment for WAS. Haploidentical family donors were selected as donor sources for a total of five patients without a suitable donor between March 2015 and March 2017. A modified transplant protocol using PTCy (50 mg/kg/day on days +3 and +4) was performed, including busulfan (16 mg/kg), fludarabine (150 mg/m2 ), and rabbit antihuman thymocyte globulin (7.5 mg/kg). The median time for neutrophil recovery over 1,000 × 103 /mm3 was 15 days (range, 12-18 days), and that for keeping platelets counts over 50,000/mm3 was 27.5 days (range, 20-35 days). The median follow-up was 2.1 years (range, 1.4-2.5 years). Two patients developed grade I acute graft-versus-host disease (GVHD), and one patient had limited chronic GVHD. All five patients are alive and independent of platelet infusion with 100% donor chimerism. Our pilot study suggests that HSCT with modified PTCy is a safe and effective treatment for WAS, which needs further clinical practice and research.

Yue Y ，Shi X ，Song Z ，Qin J ，Li J ，Feng S ，Liu R ... -  《-》

Successful Reduced Intensity Conditioning Alternate Donor Stem Cell Transplant for Wiskott-Aldrich Syndrome.

Thakkar D ，Katewa S ，Rastogi N ，Kohli S ，Nivargi S ，Yadav SP ... -  《-》

Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells.

Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/μL of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting.

Cieri N ，Greco R ，Crucitti L ，Morelli M ，Giglio F ，Levati G ，Assanelli A ，Carrabba MG ，Bellio L ，Milani R ，Lorentino F ，Stanghellini MT ，De Freitas T ，Marktel S ，Bernardi M ，Corti C ，Vago L ，Bonini C ，Ciceri F ，Peccatori J ... -  《-》

Haploidentical Stem Cell Transplantation With Post-transplant Cyclophosphamide for Pediatric Acute Leukemia is Safe and Effective.

Haploidentical family donor is universally available and is fast emerging as an alternative donor choice for children with leukemia needing hematopoietic stem cell transplant (HSCT). Here we describe our experience of treating children with acute leukemia by haploidentical HSCT with posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the outcome data of 17 children with acute leukemia who underwent related haploidentical HSCT. Fifteen were in complete remission (CR) before HSCT: CR1-6, CR2-7, and CR3-2 and 2 were not in remission. Donors were mobilized with granulocyte colony stimulating factor. The conditioning was nonmyeloablative in 4 and myeloablative in 13. All received PTCy 50 mg/kg on days 3 and 4 as graft-versus-host disease (GVHD) prophylaxis along with tacrolimus or cyclosporine and mycophenolate mofetil. A median of 8.94 million of CD34+ cells/kg was infused. All patients were engrafted for neutrophil and platelets, except 1 child with refractory acute myeloid leukemia disease who relapsed before engraftment. Five children relapsed (4 died and 1 child with CD20-positive leukemia is disease free after Rituximab therapy). There was 1 transplant-related mortality due to grade IV GVHD. Remaining 11 patients are in CR. Acute GVHD was seen in 4 patients. Of 4, 3 children later developed chronic GVHD and all are alive and disease free. Three of 4 children who received nonmyeloablative conditioning have relapsed. Overall survival is 70.5% and event-free survival is 64.7%. Median follow-up of all patients was 393 days. Haploidentical HSCT with PTCy is a safe and effective therapy for children with acute leukemia. Myeloablative conditioning and chronic GVHD lead to improved disease-free survival.

Sharma A ，Rastogi N ，Chatterjee G ，Kapoor R ，Nivargi S ，Yadav SP ... -  《-》