Role of Allogeneic Hematopoietic Stem Cell Transplantation in t(4;11) Positive Acute Lymphoblastic Leukemia (ALL): A Retrospective Multicenter Study of the Italian Association of Pediatric Hematology and Oncology (AIEOP)

Background. Disease-free survival (DFS) for children with ALL exceeds 80%. Nevertheless, the cure rate can be significantly lower in patients with specific chromosomal translocations, confering poor prognosis. The t(4;11) translocation can be detected in 1-3% of children with ALL and is associated with aggressive clinical course and high risk of treatment failure and relapse. Consequently, patients with t(4;11) may be offered allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR), although the role of HSCT in this setting is still unclear.

Patients and Methods. Data on children with t(4;11) positive ALL treated with allogeneic HSCT in AIEOP Centers from 1990 to 2013 were retrospectively collected, and the impact of patient- and treatment-related variables on the clinical outcome was evaluated. A total of 72 consecutive children with t(4;11) positive ALL were analyzed; 33 patients were males and 39 female. The median age at diagnosis was 11 months (range, 1.2 months - 15 years). 38 patients (53%) had an age at diagnosis < 12 months (defined as infants) and 22 were younger than 6 months at diagnosis. The median WBC count was 167x10⁹/l. The majority of infants (30 patients) were enrolled into Interfant 99 and 06 protocols, while the 34 children older than 12 months of age were enrolled into AIEOP 95, 2000, R-2006 and 2009 protocols, respectively. 46 children (64%) were transplanted in first CR, 18 (25%) in second CR and the remaining 8 (11%) in a more advanced disease phase. 35 patients received HSCT from a matched unrelated donor (MUD), 28 from a matched family donor (MFD) and 9 from a partially matched family donor (PMFD). TBI was used in 40% of patients, while a busulfan-based conditioning regimen was used in 56% of cases.

Results. 5-year overall survival (OS) and DFS were 54% (42-67) and 47% (35-60), respectively. Transplant-related mortality (TRM) and relapse incidence (RI) were 20% (13-33) and 32% (23-46), respectively. DFS by donor type was as follow: MFD 51%, MUD 52% and PMFD 22%, respectively (P = 0.04). TRM by donor type was 20% for MFD, 14% for MUD and 44% for PMFD, respectively (P = 0.03). DFS was 60% for children transplanted in 1^st CR, 30% for patients transplanted in 2^nd CR and 25% for those with more advanced disease (P = 0.002). DFS was 40% for children with an age at diagnosis < 6 months, 46% for those with an age at diagnosis between 6 and 12 months, 40% for the 12-24 months group and 57% for patients with an age at diagnosis > 24 months (P = N.S.). DFS was 61% for children receiving TBI and 39% for those treated with a chemo-based conditioning (P = 0.089).

Conclusions. Our analysis suggests that HSCT in first remission is a valid therapeutic option for children with t(4;11) positive ALL. Patients transplanted in 1^st CR, as well as those receiving a TBI-based conditioning regimen, had a better outcome. MFD and MUD transplants were associated with a similar DFS probability.