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Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia: The Cibmtr Experience

Track: Pediatric BMT Program
Thursday, February 27, 2014, 5:30 PM-7:00 PM
Grapevine A+C (Gaylord Texan)
Parinda A. Mehta, MD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Mary Eapen, MBBS, MS , CIBMTR, CIBMTR/Medical College of Wisconsin, Milwaukee, WI
Mei-Jie Zhang, PhD , Biostatistics, Medical College of Wisconsin, Milwaukee, WI
Wensheng He, PhD, MS , CIBMTR, Medical College of Wisconsin, Milwaukee, WI
Adriana Seber, MD , Instituto de Oncologia Pediatrica, Sao Paulo, Brazil
Carrie L. Kitko, MD , University of Michigan, Ann Arbor, MI
Gregory A. Hale, MD , All Children's Hospital, St. Petersburg, FL
Stella M. Davies, MBBS, PhD , Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Audio File Recorded Presentation

Children with hypodiploid ALL have inferior outcomes with chemotherapy despite intensive risk adapted treatment. A case series of pediatric hypodiploid ALL (n=139) with <45 chromosomes treated by 10 different national ALL study groups (Nachman et al; 2007), reported an 8-year event free survival (EFS) of 38.5% and overall survival (OS) of 49.8%.  Patients with fewer than 44 chromosomes fared significantly worse than those with 44 chromosomes (EFS of 30% vs. 52%, p=0.01). A similar report from the Medical Research Council (MRC) included 226 children and adults treated with chemotherapy (Harrison et al, 2004). Patients with 42-45 chromosomes (n=153) had a 3 year survival of 66% compared to 29% in those with 25-39 chromosomes.   

We conducted a retrospective study of 78 children with hypodiploid ALL who underwent HSCT between 1990 and 2010 and reported to CIBMTR, to determine whether outcomes might be improved with transplant.

Median age at HSCT was 10 years (range 3-18). Thirty nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes and 27 (35%) had 45 chromosomes. Forty three (55%) patients were transplanted in CR1 while 35 (45%) were transplanted in ≥CR2. Twenty nine patients (37%) received a graft from a related donor, 34 (44%) an unrelated donor and 15 (19%) cord blood. Demographics and transplant characteristics were similar in those with chromosomes ≤43 or ≥44 and those transplanted with early or late disease (CR1 or CR2 and beyond). All patients received a myeloablative conditioning regimen.

Multivariate analysis confirmed both disease status and number of chromosomes were independently associated with mortality; mortality risks were higher for transplants in CR2 (HR 2.16, p=0.05) and when chromosomes were <=43 (HR 2.15, p=0.05).The 5-year estimates of DFS, OS, relapse, and treatment related mortality (TRM) for the entire group, those in CR1 and for those in CR1 with ≤43 chromosomes are shown in Table 1. In the group with ≥44 chromosomes (n=13), 3 patients died and 10 were alive at last contact (9 disease free and 1 with relapsed disease). Despite the obvious limitation of small numbers of patients and the retrospective nature of our study, our results suggest that compared to historical results from chemotherapy only treatment, pediatric patients with hypodiploid ALL, may have improved outcomes when transplanted in CR1, and benefit may be most notable in those with ≤43 chromosomes.

Table 1. HSCT outcomes in children with hypodiploid ALL at 5 years

 

 

DFS % (range)

OS % (range)

Relapse% (range)

TRM% (range)

 

<------------------------- 5 year estimates ------------------------->

All patients

51 (40-62)

56 (44-67)

27 (18-38)

22 (14-32)

 

Patients in CR1

 55 (40-70)

58 (43-72)

26 (14-40)

20 (9-33)

 

 

CR1 patients with ≤43 chromosomes

 47 (29-66)

50 (32-69)

30 (15-47)

23 (9-41)

 

Disclosures:
Nothing To Disclose
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