Safety and Efficacy of Non-Myeloablative (NMA) Melphalan-Based Conditioning for Haploidentical Allogeenic Stem Cell Transplantation (HaploSCT) in Patients with Advanced Lymphoma

Safety and Efficacy of Non-Myeloablative (NMA) Melphalan-Based Conditioning for Haploidentical Allogeneic Stem Cell Transplantation (HaploSCT) in Patients with Advanced Lymphoma

Jonathan E Brammer, Issa Khouri, Sameh Gaballah, Celina Ledesma, Paolo Anderlini, Borje S. Andersson, Uday R. Popat, Qaiser Bashir, Chitra Hosing, Richard E. Champlin, Stefan O. Ciurea

Introduction

Haploidentical transplantation with post-transplant cyclophosphamide (PTCy) using the non-myeloablative (NMA) conditioning regimen with Flu/Cy/TBI has been associated with low treatment-related mortality (TRM) for lymphoma patients. We investigated a more intense, melphalan-based regimen in an attempt to improve disease control post-transplant for advanced lymphoma patients.

Methods

All patients who received a bone marrow HaploSCT at MD Anderson for high-risk lymphoma/CLL after 2009 were reviewed. Initially, patients received myeloablative (MA) conditioning with fludarabine and melphalan 140 mg/m2 (FM140) +/- thiotepa 5-10 mg/kg. Due to concerns of increased TRM, a lower intensity conditioning regimen with melphalan 100 mg/m2 (FM100) +/- thiotepa 5 mg/kg or 2Gy TBI was adopted. Rituximab was included for CD20+ disease. GVHD prophylaxis consisted of tacrolimus/MMF/PTCy, as previously described. One patient was treated with the Flu/Cy/TBI regimen. Univariate comparisons were done utilizing the log-rank test.

Results

Nineteen patients, with a median age of 45 years (range 20-62) underwent HaploSCT for advanced lymphoma. Characteristics of these patients are described in the Table. Seventy-four percent of patients were not in remission at transplant. Of the patients not in CR/CRU at transplant, 9/14 (64%) remain alive. Engraftment occurred in 18 patients (95%), with one incident of primary graft failure. Best chimerism was full donor in 16/19 (84%) of patients. Cumulative incidence (CI) of grade II-IV acute GVHD was 44% at day 100. Only 2 patients developed chronic GVHD, 1 limited, 1 extensive. After a median follow-up time of 22 months, median OS and PFS for this group was 63% and 52%, respectively. The 2-year CI of TRM and disease relapse were 11% and 26%. PFS at 2 years for patients receiving NMA conditioning was 70% compared to 31% in patients receiving MA conditioning (p=0.29).

Conclusions

FM100 regimen appears at least as effective as FM140 as conditioning for patients with advanced lymphoma receiving HaploSCT, with excellent disease control and low TRM and should be further investigated in prospective clinical trials.

Characteristic	N (%)
Sex Male Female	13 (32) 6   (68)
Lymphoma Type Hodgkin's NHL CLL/PLL	7   (37) 7   (37) 5   (26)
Disease Status at Transplant CR/CRU PR SD PD	5   (26) 10 (53) 3   (16) 1   (5)
Conditioning Intensity MA NMA	11 (58) 8   (42)
Donor Relation Parent Child Sibling	4   (21) 4   (21) 11 (58)