Non-TBI, Non-ATG Containing Fludarabine-Based Regimen for Unrelated Allogeneic Reduced Intensity Transplantation.
Authors: Nakamae Hirohisa , Nakane Takahiko , Koh Hideo , Takaoka Yasunobu , Sakamoto Erina , Kanashima Hiroshi , Ichihara Hiroyoshi , Nakamae Mika , Koh Ki-Ryang , Yamane Takahisa , Hino Masayuki 
Published: October 2019

Optimal conditioning for unrelated allogeneic reduced intensity stem cell transplant (u-RIST) has not been sufficiently established yet. Most reported conditioning regimens for u-RIST include anti-thymocyte globulin (ATG), low dose total body irradiation (TBI) or Campath-1H. However, even low dose TBI can evoke additional toxic effects, and ATG or Campath-1H can over-suppress graft versus lymphoma or leukemia effects or immune reconstitution which causes opportunistic infections. Whether or not TBI, ATG or Campath-1H is indeed needed for engraftment in u-RIST, has been not yet determined.Å@The magnitude of immunnosuppression and the intensity of conditioning to facilitate engraftment are definitely different in each patient. Here we report fludarabine-based conditioning without TBI, ATG and Campath-1H for u-RIST in patients who received prior chemotherapy.

In this study, we enrolled 14 patients (22 to 69 years old) with hematologic diseases who received unrelated bone marrow transplantation from September 2002 to April 2006 at our institution. These patients included 5 with acute myeloid leukemia, 4 with acute lymphoblastic leukemia, 1 with myelodysplastic syndrome, 2 with non-Hodgkin’s lymphoma, 2 with adult T-cell leukemia (ATL), and one patient with plasma cell leukemia. Ten (71%) patients were at the advanced stages of their disease. All patients received at least one course of prior chemotherapy. The median course of prior chemotherapy was 5 (1–12). The reduced-intensity conditioning for 12 patients excluding ATL consisted of fludarabine 150mg/m2 and busulfan 8 mg/m2. Whereas, the reduced-intensity conditioning for 2 patients with ATL included busulfex 8 mg/m2 instead of busulfan. As a prophylaxis for acute graft-versus-host disease (aGVHD), 12 patients received both cyclosporine A and short-term methotrexate; 3 received CyA alone because of apparent residual or active disease.

In all patients, neutrophil and platelet engraftment were achieved rapidly. The median time of engraftment in neutrophil and platelet was 16.5 days (11–26) and 23.5 days (15–38), respectively. In 10 (71%) of 14 patients, complete chimerism was achieved within 60 days of transplant. Regimen related toxicity in this conditioning was minimal and grade IV of non-hematological regimen related toxicity did not appear. Grade III stomatitis and liver dysfunction occurred in 3 patients and one patient, respectively.

Four out of 5 patients with grade II–IV received HLA genotype 1-locus mismatched transplants. In 5 patients with grade II–IV, acute GVHD was manageable only with additional steroids treatments except one patient with grade IV acute GVHD causing early death. In this study, day100-transplant related mortality (TRM), 1 year-TRM, event free survival, and overall survival were 7%, 24%, 70%, and 53 %, respectively. These results show that non-TBI, non-ATG containing fludarabine based-regimen for u-RIST may be less toxic and feasible at least for patients who received prior chemotherapy.