Second allogeneic hematopoietic cell transplantation (alloHCT) for patients with acute lymphoblastic leukemia (ALL) who experienced relapse after first alloHCT may be associated with poor outcomes, according to research published in the British Journal of Haematology.

The Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT) conducted a retrospective survey of 245 patients with B-cell (B-ALL) or T-cell ALL (T-ALL) who underwent second alloHCT within a year of experiencing relapse following first alloHCT. The goal of the study was to characterize risk factors and outcomes of second alloHCT to inform the feasibility of performing second alloHCT in patients at high risk.

Median time from first to second alloHCT was 463 days. The majority of patients (93%) received peripheral blood. The donor was a matched sibling for 41% of patients and unmatched for 59% of patients. Prior to second alloHCT, 64% of patients were in second complete remission and 36% were in first relapse.

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After a median follow-up of 58 months, leukemia-free survival (LFS) was 20% at 2 years and 12% at 5 years, and overall survival (OS) was 30% at 2 years and 14% at 5 years. The 2-year and 5-year relapse incidences were 56% and 63%, respectively, while the 2-year and 5-year nonrelapse mortality rates were 24% and 26%, respectively.

There were 181 deaths reported following second alloHCT. Grade 2 or higher acute graft-vs-host disease (GVHD) occurred in 34% of patients, with 18% of patients experiencing grade 3 or higher GVHD. Rates of chronic GVHD were 38% at 5 years and 21% extensively. Time from first relapse to second alloHCT was associated with both acute (P =.02) and chronic GVHD (P =.015).

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Time from first alloHCT to first relapse was associated with relapse incidence (P =.003), improved LFS (P =.05), 2-year OS (P <.012). Karnofsky performance status (KPS) of 90 or higher was associated with improved LFS (P =.01) and 2-year OS (P <.001). GVHD incidence (P =.02). Nonrelapse mortality was not found to be associated with any risk factors; donor type was not to found to influence any outcomes of second alloHCT.

Few patients achieved long-term LFS. Thus, the authors noted that “better disease control, relapse monitoring, patient selection, and prophylactic relapse-prevention strategies are urgently needed to improve outcomes of these very high-risk groups of patients.”


Nagler A, Labopin M, Dholaria B, et al. Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation [published online May 22, 2019]. Br J Haematol. doi:10.1111/bjh.15973