A Prospective Feasibility Trial of Unrelated Bone Marrow Transplantation with Reduced Intensity Conditioning Regimen for Elderly Patients with Adult T-Cell Leukemia/Lymphoma (ATL),
Authors: Eto Tetsuya , Choi Ilseung , Tanosaki Ryuji , Takatsuka Yoshifusa , Utsunomiya Atae , Takemoto Shigeki , Taguchi Jun , Fukushima Takuya , Kato Koji , Teshima Takanori , Suehiro Yoko , Yamanaka Takeharu , Okamura Jun , Uike Naokuni 
Published: October 2019

Abstract 4163

Introduction:

ATL is a peripheral T-cell malignancy that is caused by human T-lymphotropic virus type 1 (HTLV-1) infection and commonly affects individuals at an average age of 60 years. Since the prognosis of elderly patients with the disease has been unsatisfactory by conventional chemotherapy, we had so far conducted two clinical trials to evaluate the feasibility of allogeneic hematopoietic stem cell transplantation (allo-SCT) using G-CSF-mobilized peripheral blood stem cells from HLA-identical sibling donors combined with reduced-intensity conditioning regimen (RIC) and reported promising results (Okamura et al, Blood, 2005; Tanosaki et al, Biol Blood Marrow Transplant, 2008; Choi et al, Bone Marrow Transplant, 2011). The availability of suitable sibling donors, however, will become more and more difficult due to the aging as well as complications of donors. In this study, we conducted a clinical trial of an alternative strategy of allo-SCT using bone marrow cells from unrelated donors with RIC for elderly patients with ATL.

Study design:

Patients between 50 and 65 years of age who satisfied the diagnostic criteria for acute or lymphoma type ATL and had no available HLA matched family donors were eligible. It was required at the time of registration that they were in either complete remission (CR) or partial remission after chemotherapy and had an unrelated donor whose HLA-A, B and DR loci were genotypically matched. DR one locus-mismatched donors were acceptable. All patients were needed their written informed consent to participate in this study which was approved by the institutional review board of each participating institution. The conditioning regimen consisted of fludarabine (180 mg/m2), intravenous busulfan (6.4 mg/kg) and low dose total body irradiation (2Gy). Bone marrow grafts from the Japan Marrow Donor Program were transplanted on day 0. To prevent graft versus host disease (GVHD), tacrolimus (0.03 mg/kg/day) and short-term methotrexate were administered. The primary endpoints of the study were both engraftment, as judged by the achievement of complete donor chimerism before day 100, and survival at day 100 after SCT. The severity of GVHD was graded according to the consensus criteria. The degrees of donor-recipient chimerism and HTLV-1 proviral DNA in peripheral blood mononuclear cells were quantified by published methods.

Results and discussion:

Fifteen patients were registered between February 2009 and April 2011 at 8 institutions in Japan. The median age of the patients was 58 (range, 51–62). Seven were male, 12 had acute type, and 7 were in CR. Median period from diagnosis to SCT was 7 months (range, 4–12). There were 9 pairs of patient and donor with HLA fully matched, and HLA-DR one locus-mismatched pairs were six. All donors were negative for anti-HTLV-1 antibody. One patient who developed an early relapse failed to achieve complete donor chimerism before day 100, resulting in 14 out of 15 patients with complete donor chimerism. One other patient developed an early treatment-related death on day 34 due to sever thrombotic microangiopathy-related toxicities. Thus, 13 of 15 patients achieved the primary objective. Disease progression was observed in 3 patients at a median follow-up period of 530 (range, 108–864) days. Acute GVHD was observed in 10 of 15 patients, where 2/6/2 patients experienced grade 3/2/1. Kinetics of the HTLV-1 proviral load after SCT showed that it decreased to an undetectable level (< 0.5 copies) in 10 of 14 patients who survived beyond 100 days. In conclusion, this study firstly indicated that SCT using bone marrow cells with RIC from unrelated donors is a feasible therapeutic procedure for elderly patients with ATL.

Disclosures:

No relevant conflicts of interest to declare.