Outcome of patients with acute undifferentiated leukemia after allogeneic hematopoietic stem cell transplantation

The World Health Organization (WHO) has categorized acute undifferentiated leukemia (AUL) as a rare subtype of acute leukemias of ambiguous lineage (ALAL). The prognosis of AUL is considered poor and it expresses no known lineage-specific marker [1,2]. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can potentially cure various hematological malignancies, little is known about the transplant modality and outcomes of patients with AUL. Most published reports to date have analyzed the clinical characteristics and prognosis of AUL together with those of mixed-phenotypic acute leukemia (MPAL) although they have quite different clinical characteristics [3–5]. Therefore, these studies might not be particularly informative for patients with AUL. Here, we analyzed the clinical outcomes of 10 patients with AUL after allo-HSCT at our institution. We retrospectively reviewed 911 patients with acute leukemia who were admitted to our institution between April 2005 and March 2017. Consensus diagnostic criteria for AUL have not yet been established. Therefore, we defined AUL based on the WHO classification [2] as leukemic cells that were not positive for any lineage-specific markers (myeloid lineage: myeloperoxidase [cytochemistry, immunohistochemistry, or flow cytometry]; B cell lineage: CD19, CD79a, or cytoplasmic CD22; T cell lineage: cytoplasmic CD3 or surface CD3). Our institutional committee on research ethics approved the study (approval number: 1973), which proceeded according to the Declaration of Helsinki. Transplant procedures have been described in detail elsewhere [6]. Generally, myeloablative conditioning mainly included a total body irradiation (TBI) regimen (12Gy) in combination with cyclophosphamide (CY) at 120mg/kg, or a non-TBI regimen that included intravenous busulfan at 12.8mg/kg, and CY at 120mg/kg. The preparative regimen for the reduced-intensity procedure consisted of fludarabine (30mg/m for 6 d), melphalan (40mg/m for 2 d), and TBI (4 Gy). The patients were given intravenous infusion of donor hematopoietic stem cells on day 0. All patients received acute graft-versus-host disease (GVHD) prophylaxis with cyclosporine or tacrolimus and short-term methotrexate. Tacrolimus was used in cases involving either unrelated or human leukocyte antigen (HLA) mismatched transplantation. Engraftment in alloHSCT is defined as the first of three consecutive days with an absolute neutrophil count of 0.5 10/l or greater. The probability of overall survival (OS) was estimated using Kaplan–Meier product limit method. We calculated OS from the date of allo-HSCT to the last assessment for survivors. The cumulative incidence of non-relapse mortality (NRM), relapse and acute GVHD were evaluated using Gray’s method. For each estimation of the cumulative incidence of an event, death without event was defined as a competing risk. All statistical analyses were performed with EZR, a graphical user interface for R software (The R Foundation for Statistical Computing, version 2.13.0; www.r-project.org). Among the 911 patients with acute leukemia, AUL was classified in only 12 (1.3%). Among those, one patient refused to undergo allo-HSCT and another died early. Table 1 shows the characteristics of 10 patients with AUL who underwent allo-HSCT. The median age at the time of transplantation was 45 (range: 22–63) years. Seven (70.0%) and three (30.0%) patients were male and female, respectively. Marrow fibrosis was found in two (20.0%) patients, but extramedullary disease was not present in any patient. Cytochemical findings were negative for myeloperoxidase in all patients. Immunophenotyping revealed the common expression of CD34 (90.0%), HLADR (80.0%), and CD13 (60.0%), but the lineage-specific markers were absent in all patients. Cytogenetic studies of nine patients revealed chromosomal abnormalities in five (55.6%) of them. In five patients (cases 2, 4, 5, 9, and 10) with available data, polymerase chain reaction (PCR)