Unmanipulated Haploidentical Bone Marrow Transplantation and Posttransplantation Cyclophosphamide for Hematologic Malignancies after Myeloablative Conditioning

Abstract

Fifty patients with high-risk hematologic malignancies, underwent an unmanipulated haploidentical bone marrow transplantation (BMT), followed by posttransplantation high-dose cyclophosphamide (PT-CY): the myeloablative (MA) conditioning consisted of thiotepa, busulfan, fludarabine (n = 35), or total body irradiation (TBI), fludarabine (n = 15). The median age was 42 years (range, 18-66 years); 23 patients were in remission, 27 had active disease, and 10 patients were receiving a second allograft. Graft-versus-host disease (GVHD) prophylaxis consisted in PT-CY on day +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). Three patients died before engraftment, and 2 patients had autologous recovery: 45 patients (90%) had full-donor chimerism on day +30. The median day for neutrophil engraftment was day +18 (range, 13-30 days). The cumulative incidence of grade II-III acute GVHD (aGVHD) was 12%, and of moderate chronic GVHD (cGVHD) 10%. With a median follow-up for surviving patients of 333 days (range, 149-623 days), the cumulative incidence of transplantation-related mortality (TRM) was 18%, and the rate of relapse was 26%. The actuarial 22-month disease-free survival (DFS) rate was 68% for patients in remission and 37% for patients with active disease (P < .001). Causes of death were pneumonia (n = 3), hemorrhage (n = 3), sepsis (n = 3), and relapse (n = 7). In conclusion, an MA conditioning regimen followed by haploidentical BMT with PT-CY results in a low risk of aGVHD and cGVHD and encouraging rates of TRM and DFS.

Haploidentical transplantation using G-CSF-mobilized T-cell replete PBSCs and post-transplantation CY after non-myeloablative conditioning is safe and is associated with favorable outcomes

“…Despite a high median T-cell dose, aGVHD rate of 41% and cGVHD rate of 8% are comparable to those reported by other groups using more aggressive myeloablative conditioning regimens. 2,3,5 The 1-year OS of 62% and RFS of 53% are highly encouraging considering the fact that approximately one-third had prior HSCT and half of our patients underwent transplant with active disease. Although our study is limited by a small number of patients with relatively short Abbreviations: CLL/SLL = chronic lymphocytic leukemia/small lymphocytic leukemia; DLBCL = diffuse large B-cell lymphoma; F = female; M = male; NHL = non-Hodgkin lymphoma; t-MDS = therapy related myelodysplastic syndrome.…”

“…1 Recently, several groups have reported encouraging outcomes using PBSC and more intensive myeloablative conditioning regimens on this PT-CY haplo-HSCT platform. [2][3][4][5] We hypothesized that relatively high T-cell numbers in the G-CSF-mobilized PBSC graft would help in engraftment and reduce relapse rates without the need to increase the intensity of the conditioning regimen on this PT-CY haplo-HSCT platform. After an approval from our institutional review board, we retrospectively analyzed all the patients treated on this haplo-HSCT regimen since July 2009.…”

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes

“…We suppose that these results could be improved in AML patients with standard risk (that is, Intermediate cytogenetics AML in CR1), but to date, very few data of PT-Cy Haplo-SCT are available in this specific setting. The others series reporting the results of PT-Cy Haplo-SCT in the specific fields of AML or MDS included few patients (18)(19)(20)(21)(22)(23)(24)(25), with various proportion of refractory diseases (36-100%). [25][26][27] They found a PFS ranging from 39 to 72%.…”

Chronic GVHD induced GVL effect after unmanipulated haploidentical hematopoietic SCT for AML and myelodysplastic syndrome

“…Although it is a large study of unmanipulated haplo-HSCT in patients with AML and MDS, the number of cGVHD patients, particularly severe cGVHD patients, was relatively small and that might influence the accuracy of our results. Secondly, we only enrolled the haplo-HSCT recipients and our unmanipulated transplant protocol was distinct from what is observed in other haplo-HSCT performed with TCD, 25,26 posttransplant CY, 31 or regulatory T-cell admixture. 32 Thus, it would be premature to derive conclusions regarding the association between severity of cGVHD and transplant outcomes in patients with AML and MDS.…”