Long-Term Results Of Allogeneic Stem Cell Transplantation In 56 Adult Patients With Philadelphia-Positive Acute Lymphoblastic Leukemia: A 20-Year Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5521-5521
Author(s):  
Adalberto Ibatici ◽  
Fabio Guolo ◽  
Federica Galaverna ◽  
Clara Delle Piane ◽  
Alida Dominietto ◽  
...  

Abstract Background Despite the great clinical benefit from the advent of tyrosine-kinase inhibitors (TKIs) treatment for adult patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL), allogeneic hematopoietic stem cells transplantation (allo-HSCT) does not appear to be dispensable, if the optimal long-term outcome is to be achieved. However, there are only few data reported on long-term survivors with Ph+ ALL, particularly for those not receiving pre-transplant TKIs in the conventional induction therapy. In this retrospective analysis, we report on the long term outcomes of myeloablative allo-HSCT during the past 2 decades as single center experience. Data on the use of post-transplant TKIs and molecular monitoring for minimal residual disease are being collected to investigate their predictive role. Patients and methods Between 1989 and 2013, we collected 56 patients who underwent myeloablative allo-HSCT from HLA-identical siblings (n: 24), unrelated donors (n: 17), alternative donors (n: 15). Median age was 41 years (16-64). Disease phase at transplant was CR1 in 30 pts (53%), >CR1 in 26 pts. Pre-transplant TKI as part of induction therapy was given in 25 pts (44%). Conditioning regimen was TBI-based in 47 pts (83%) and chemotherapy-based in 9 pts. GVHD prophylaxis was given according to Center standard practice. Results Median follow-up was 67 months (1- 244). There were no cases of primary graft failure. Incidence of grade II-IV acute GVHD occurred in 31 pts (55%) and extensive chronic GVHD in 18 pts (32%). Transplant-related mortality was 35% at 2 years and 7 more patients died of non-relapse causes up to 12 years after transplant. The 10-year OS was 25% and significantly better for patients in CR1 vs. >CR1 (36% VS 14% - p=0,006). The 10-year DFS was 27% with no statistical difference for pts in CR1 vs. >CR1. Age at transplant and pre-transplant TKI did not affect the outcomes. Conclusions In this retrospective analysis over a 20-year time period, we show that approximately one-third of adult Ph+ ALL are cured if they undergo allo-HSCT in CR1. Therefore, we confirm that disease status at transplant has a major prognostic impact on clinical outcomes. The apparent lack of benefit of pre-transplant TKI exposure may be due to the retrospective nature of the analysis. Disclosures: No relevant conflicts of interest to declare.

2015 ◽  
Vol 56 (9) ◽  
pp. 2524-2528 ◽  
Author(s):  
José Carlos Jaime-Perez ◽  
Perla R. Colunga-Pedraza ◽  
César Homero Gutiérrez-Aguirre ◽  
Mónica Andrea Pinzón-Uresti ◽  
Olga G. Cantú-Rodríguez ◽  
...  

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4087-4087
Author(s):  
Jae-Ho Yoon ◽  
Hanwool Cho ◽  
Seug Yun Yoon ◽  
Gi June Min ◽  
Sung-Soo Park ◽  
...  

Abstract Background: Recently, a high-risk subgroup of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) called Philadelphia chromosome (Ph)-like ALL was identified in adolescents and young adults. However, there are conflicting data regarding the incidence and prognosis of Ph-like ALL in adult patients, and no data have yet been introduced in Asian countries. Aim: We tried to identify the prevalence and genetic characteristics of Ph-like ALL in adult patients with newly diagnosed BCP-ALL. Furthermore, we analyzed the clinical characteristics, long-term outcomes, and prognostic impact of Ph-like ALL compared with non-Ph-like ALL (Ph-positive ALL or BCP-other ALL). Methods: Between December 2008 and March 2016, 334 adult patients with newly diagnosed BCP-ALL who received modified hyper-CVAD chemotherapy and had suitable material for genomic analysis were included in this analysis (median age, 43 years [range, 16-65 years]). Our post-remission therapy was based on allogeneic hematopoietic cell transplantation (HCT) if a donor is available. Ph-like ALL was determined by next generation sequencing using the Archer® FusionPlex® ALL Kit (ArcherDX Inc., CO) which can detect fusions, point mutations, and expression levels in 81 genes associated with ALL and additional FISH analysis was done. Results: Overall, 48 (14.4%) of the 334 patients were Ph-like ALL, and the cohort was divided into patients with ABL1-class rearrangements (n=4), CRLF2 rearrangements (n=11), JAK2 rearrangements (n=4), other JAK-STAT sequence mutations (n=12), and RAS mutations (n=17). The remaining 286 patients had Ph-positive ALL (n=197) and BCP-other ALL (n=89; including 19 patients with KMT2A [MLL] rearrangements). No significant differences in baseline characteristics were observed between the Ph-like ALL and BCP-other ALL subgroups, whereas patients with Ph-positive ALL were older (median age, 47 vs 37 years; p=0.003) and had higher presenting leukocyte counts (median, 33.1 vs 11.4´109/L; p=0.001) compared with Ph-like ALL. The complete remission rate was somewhat different between the 3 disease subgroups (Ph-like ALL, 97.9%; Ph-positive ALL, 95.9%; BCP-other ALL, 88.8%; p=0.027). A higher proportion of patients with Ph-like ALL actually received allogeneic HCT in CR1 than patients with non-Ph-like ALL (Ph-like ALL, 91.6%; Ph-positive ALL, 84.2%; BCP-other ALL, 71.9%; p=0.007). With a median follow-up of 58.1 months (range; 6.0-121.0), outcomes of patients with Ph-like ALL were not inferior compared with outcomes of patients with non-Ph-like ALL. Disease-free survival rates at 5 years were 56.0% for Ph-like ALL, 42.6% for Ph-positive ALL, and 40.6% for BCP-other ALL (p=0.138). The 5-year cumulative incidence of relapse were 19.2% for Ph-like ALL, 35.3% for Ph-positive ALL, and 33.5% for BCP-other ALL (p=0.076). These findings were maintained when only patients receiving HCT were considered. Within the Ph-like ALL subgroup, patients with ABL1-class and CRLF2-rearrangements had worse outcomes than patients with other JAK-STAT sequence and RAS mutations. Also, patients with higher CRLF2 expression had inferior outcomes. Conclusion: Within the limitation of sample size, our data showed a different frequency of subtypes (e.g., lower incidence of CRLF2 rearrangements, higher RAS mutations) and treatment outcomes of adult patients with Ph-like ALL compared with other Western reports. Racial and ethnic differences in the patient population studied may have contributed to these differences. We also suggest that HCT-based post-remission therapy may overcome the poor prognosis of Ph-like ALL. Disclosures Kim: BMS: Research Funding; Ilyang: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Lee:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.


2010 ◽  
Vol 58 (S 01) ◽  
Author(s):  
S Kueri ◽  
B Nitsch ◽  
C Heilmann ◽  
J Schneider ◽  
C Schlensak ◽  
...  

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