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Adoptive immunotherapy, chemotherapy, and second allogeneic transplant in the treatment of post-transplant relapse of acute leukemia in children: a single center experience

Relapse of acute leukemia (AL) remains a major cause of treatment failure in allogeneic hematopoietic stem cell transplant (HSCT) in children. The prognosis of patients with post-transplant relapse is extremely poor [1–4]. Current treatment options include chemotherapy (CHT), adoptive immunotherapy (AI), and second allogeneic transplant. Previously reported studies showed that second allogeneic HSCT may be a reasonable treatment option in selected patients [1–6]. Between January 1994 and December 2007, a total of 132 children with acute leukemia (acute lymphoblastic leukemia [ALL]: 92, acute myeloid leukemia [AML]: 37, and acute biphenotypic leukemia [ABiL]: 3) were transplanted at our institution. The median age at first HSCT was 9.4 years (range: 1.1– 20.5). Forty-one patients with high-risk leukemia (21 ALL, 20 AML) underwent HSCT in the first complete remission (CR1). The indication for HSCT in CR1 was based on criteria of the current treatment protocols (BFM [Berlin–Frankfurt–Munich], Interfant, EsPhALL [European intergroup study on post-induction treatment of PhþALL]). Seventy-nine patients were transplanted in second or higher remission (64 ALL, 13 AML, two ABiL), and 12 children in partial remission (PR) with55% blast cells in the bone marrow but without full recovery of hematopoiesis (five ALL, five AML, two ABiL; three PR1, one PR2, eight PR3). The median follow-up of surviving patients was 77 months (29–193). Donors were human leukocyte antigen (HLA)-identical siblings (49), unrelated donors (74), matched family donors (three), or mismatched family donors (six). Overall survival (OS) 3 years after HSCT for all transplanted patients was 54.5+ 4.3%, and eventfree survival (EFS) was 47.7+ 4.3%. Twenty-nine patients (22%) died due to transplant related mortality (TRM): graft-versus-host disease (GVHD) (seven), infectious complications (18), or toxicity (four). Post-transplant relapse of AL following first allogeneic HSCT was documented in 42 patients (32%; 29 ALL, 12 AML, one ABiL) at a median of 6.8 (range: 1–36) months post-HSCT. Intensive therapy of post-transplant relapse was not attempted in 22 patients: 17 patients developed a relapse less than 6 months after HSCT (less than 3 months in nine); three patients had been transplanted in CR3 and were heavily pretreated; one patient recurred with extramedullary disease 7 months after HSCT and developed a subsequent hematological relapse; and one patient’s parents did not consent to further therapy. Intensive treatment of hematological relapse was initiated in 20 patients (48%): 11 ALL, eight AML, and one ABiL after a median of 13 (range: 6– 36) months after HSCT (Figure 1). Chemotherapy was administered to 10 patients (six ALL, four AML), chemotherapy combined with donor lymphocyte infusion (DLI) to four patients with ALL, gemtuzumab ozogamicin to four patients (one ABiL,