Allogeneic Transplant for Acute Biphenotypic Leukemia: Characteristics and Outcome in the CIBMTR Database

Acute biphenotypic leukemias (bearing markers of myeloid and lymphoid origin, ABiL) are rare (2- 5% of all acute leukemias) and are considered puzzling both with regard to their cell of origin as well as to the optimal treatment approach. The diagnostic criteria for ABiL were revised by the World Health Organization (WHO) in 2008. In the pediatric age group, the prognosis of ABiL is reported to be intermediate between acute lymphoblastic and acute myeloid leukemia. In the adult age group, ABiL generally has an unfavorable prognosis. As far as allogeneic transplant for ABiL is concerned, only small series of cases have been published to date.

In the current study, the CIBMTR database was queried for patients with ABiL who received an allogeneic transplant between 1996 and 2013 being younger than 70 years of age (n=468). Patients with primary induction failure (n=19) and transplanted in relapse (n=27) were excluded. After detailed review of pathology, cytogenetic and flow cytometry reports, of 241 cases submitted as ABiL, those without complete data to confirm WHO criteria (n=157) were excluded. Of 84 cases with complete immunophenotyping data for review, 48 co-expressed Myeloid and B-lymphoid markers (M+B) and 28 Myeloid and T-lymphoid markers (M+T). The median age of the patients was 19 years, 56% were male, the median WBC at diagnosis was 17 000, 36% received a bone marrow, 33% a peripheral blood graft and 31% cord blood stem cells. The conditioning regimen was myeloablative in 87% and RIC/NMA in 10% of cases.

Treatment outcomes are shown below:

Treatment related mortality	n=80
1-year		15 (8-24)%
2-year		17 (9-26)%
3-year		17 (9-26)%
Disease free survival	n=80
1-year		70 (60-80)%
2-year		62 (50-72)%
3-year		60 (48-71)%
Overall survival	n=84
1-year		78 (69-87)%
2-year		69 (59-79)%
3-year		65 (54-75)%

The 3-year overall survival was 61% (95%CI, 46-74%) in My+B group and 73%  (95%CI, 54-88%) in My+T group. At three years post transplant, 75%, 48%, and 60% survival rates were observed in younger than 20, 20-40, and older than 40 years age groups, respectively. No notable differences in 3-year overall survival among those transplanted in CR1 and CR2 (64% and 69%, respectively). Patients with normal/intermediate cytogenetics (n=44) and those with bcr/abl+/poor cytogenetics (n=27) had similar 3-year survival rates: 62% and 70%, respectively. In conclusion, allogeneic transplant is a valid treatment option for patients with ABiL and should be explored in patients without significant comorbidities. A study in a larger context is planned.