Allogeneic Hematopoietic Stem Cell Transplantation Overcomes the Adverse Prognostic Impact of CD20 Expression In Both Adult and Pediatric Acute Lymphoblastic Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1681-1681
Author(s):  
Veronika Bachanova ◽  
Karamjeet Sandhu ◽  
Daniel J. Weisdorf ◽  
Michael Verneris ◽  
Michael J Burke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Disease Recurrence ◽  
Hematopoietic Stem ◽  
Cd20 Expression

Abstract Abstract 1681 The heterogeneous expression of CD20 antigen on leukemic blasts may harbor prognostic value and therapeutic potential. CD20 positivity (CD20+) has been recently associated with disease recurrence and shorter overall survival in adults with pre-B acute lymphoblastic leukemia (ALL). The influence of CD20 expression on outcomes following allogeneic donor hematopoietic stem cell transplantation (HCT) is not known. Results: We analyzed CD20 expression on pre-B ALL marrow blasts at diagnosis in 157 consecutive patients who underwent allogeneic HCT in first or second complete remission (CR) from 1999–2010. Thirty-two patients with no available flow cytometry data were excluded. Out of 125 evaluable patients, 52 (42%) were < 20 years of age; 73 (58%) were ≥20. All patients had high risk ALL and were in CR at HCT (57% in CR1, 43% in CR2). A majority of patients were Ph+ (60%) and received myeloablative conditioning (84%). Grafts were from sibling (36%), unrelated umbilical cord blood (UCB) (59%) and matched adult URD (5%). CD20+, defined as >20% expression on marrow blasts, was observed in 58 (46%) patients. 55% of children and 39% of adults were CD20+ and expression was similar in CR1 & CR2. Gender, donor source (sibling vs UCB), patient CMV serostatus, cytogenetics (Ph+ vs other), and conditioning (myeloablative vs reduced intensity) was similar in CD20+ and CD20- groups. Disease-free survival (DFS) at 3 years was 48% (95% CI 39–57%) for all patients; 42% (95% CI 30–54%) for CD20- patients, and 55% (95% CI 40–67%) for CD20+ patients (p=0.14). CD20+ expression did not significantly impact relapse rate or DFS in adults (Table) while in patients <20 years CD20+ expression was associated with a slightly favorable relapse rate. Similar overall survival (OS) and DFS was seen in both age groups, independent of CD20 expression. Treatment-related mortality was unaffected at 18% (95% CI 9–27%) and 19% (95% CI 9–29%) in CD20+ and CD20- cohorts, respectively (p= 1.00). In adjusted multivariate regression, the CD20+ group had a slightly but not significantly lower risk of relapse (RR 0.54 [0.27-1.09]; p=0.09), yet similar OS (RR 0.66 [0.38-1.14], p=0.13) and DFS (RR 0.67 [0.39-1.14], p=0.14) compared to the CD20- group. Conclusion: Pre-B ALL with a CD20+ immunophenotype reportedly confers higher risk of disease recurrence and unfavorable OS with conventional chemotherapy. Our data demonstrates that the poor prognosis associated with CD20+ ALL blasts is overcome by allogeneic HCT. In addition, post-HCT survival is promising in both adults and children, independent of CD20 expression. CD20 targeting monoclonal antibodies may further improve these outcomes. Disclosures: No relevant conflicts of interest to declare.

The Use of Imatinib with Chemotherapy and Allogeneic Hematopoietic Stem Cell Transplantation Improves Survival of Philadelphia Positive Acute Lymphoblastic Leukemia in Adults

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3653-3653
Author(s):  
Josefina Perez-Nuñez ◽  
Antonio Jimenez-Velasco ◽  
Katy Hurst ◽  
Manuel Barrios-Garcia ◽  
MJ Moreno ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Philadelphia positive acute lymphoblastic leukemia (Ph + ALL) accounts for approximately 20% -30% of all adult ALL. The prognosis of patients with Phi + ALL is unfavorable when treated with standard chemotherapy schemes, presenting a long-term survival of 15% -20%. Since the introduction of Imatinib (IM) to treatment regimens the survival of these patients has improved, although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option. We conducted a retrospective analysis of Ph + ALL patients before and after IM became available in order to analyze the impact of IM on survival in adult Phi + ALL. Patients and methods Between April 1997 and April 2013 we diagnosed 120 over 15 year old patients with ALL (B and T lineage), 31 (25.8%) of which were Phi +, all B lineage. Of these 31 cases, 30 were treated with protocols from Spanish group PETHEMA with curative intent. 14 of them (47%) were treated with chemotherapy and Imatinib (IM cohort) and 16 (53%) with chemotherapy (pre-IM cohort). In 17 of the 30 cases allogeneic HSCT was performed, 7 in the pre-IM cohort and 10 in the IM cohort. In the post-transplant period, two patients were treated with Dasatinib due to positive minimal residual disease (BCR-ABL1 positive). The probabilities of overall survival (OS) (death) and event free survival (EFS) (no response, relapse or death) were estimated using the Kaplan-Meier product limit method. Differences between groups were tested using the X2 test. Univariate analysis was performed using Cox regression models or log-rank test. Multivariate analysis was performed using Cox proportional hazards regression model. The study was conducted in accordance with the Declaration of Helsinki. Results The median age was 38 years (range, 15-66 years), 17 patients were males and 13 females. The whole series survival was 32.4 ± 9.2%. The OS mean of the pre-IM cohort was 3.1 years (CI 95%, 0.5-5.7) and 6.9 years (CI 95%, 4.4-9.4) in the IM cohort (figure 1). The main characteristics of both groups are reflected in Table 1. When we analyzed the EFS, the variables that influenced it were being treated with IM (48% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.03), having received an allogeneic HSCT (45% versus 8%, p = 0.004) and being in first complete remission before allogeneic HSCT (51% versus 0%, p <0.001). In the analysis of OS, the only variables with prognostic significance were: treatment with IM (63% in the IM cohort versus 12.5% in the pre-IM cohort, p = 0.01) and having received an allogeneic HSCT (55 % versus 0%, p <0.001). When the 17 patients that received allogeneic HSCT were analyzed separately, OS in the pre-IM cohort was 29 ± 17% versus 79 ± 13% in the IM cohort (p = 0.057). Table 1. Patient characteristics (N=30) Characteristic Pre-IM cohort(N=16) IM cohort(N=14) P Female/Male 7/9 6/8 0.96 Age ² 40 years 12 (75%) 10 (71%) 0.82 ³ 50 x109/L WBC 8 (50%) 4 (29%) 0.23 Transcript type: e1a2 b2a2/b3a2 12 (75%) 4 (25%) 11 (79%) 3 (21) 0.83 Morphological CR after induction 13/15 (88%) 13/13 (100%) 0.17 No. of Allo-HSCT 7 (44%) 10 (71%) 0.13 CR pre Allo-HSCT: 1CR 2CR 5 (71%) 2 (29%) 10 (100%) 0 (0%) 0.07 Relapse 8/13 (61.5%) 4/13 (31%) 0.12 Exitus 14 (87.5%) 5 (36%) 0.003 Abbreviations: IM, imatinib. WBC, white blood cells. CR, complete remision. Allo-HSCT, allogenetic hematopoietic stem cell transplantation. Figure 1 Figure 1. Conclusions In our study we show how adult Phi + ALL patients who are treated with chemotherapy associated with IM and subsequently receive an allogeneic HSCT exhibit a higher overall survival rate than those treated in the pre-IM era. Although Phi + ALL is still considered of very high risk, in our series of patients treated in the IM era, with a follow-up of over 7 years, overall survival was of 63%, higher than that of historical series of adults with Phi negative ALL. This work has been financed by a grant from the Malaga Association for Research in Leukemia "AMPILE" and the FIS 11-01966 project. Disclosures No relevant conflicts of interest to declare.

scholarly journals Allogeneic hematopoietic stem cell transplantation overcomes the adverse prognostic impact of CD20 expression in acute lymphoblastic leukemia

Blood ◽  
2011 ◽  
Vol 117 (19) ◽  
pp. 5261-5263 ◽  
Author(s):  
Veronika Bachanova ◽  
Karamjeet Sandhu ◽  
Sophia Yohe ◽  
Qing Cao ◽  
Michael J. Burke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Confidence Interval ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Cd20 Expression

Abstract CD20 expression is associated with early recurrence and inferior survival in precursor-B acute lymphoblastic leukemia patients treated with chemotherapy. Whether CD20 influences outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unknown. We analyzed CD20 expression on blasts at diagnosis in 157 patients who underwent allo-HSCT in the first complete remission (57%) or the second complete remission (43%). Of 125 evaluable patients, 71 were ≥ 20 years of age. CD20 expression was observed in 58 patients (46%; 52% of children, 39% of adults). There was no association between age, Ph+ status, white blood cell count at diagnosis, and CD20 positivity. After allo-HSCT, disease-free survival at 5 years was 48% for all patients, 55% (95% confidence interval 40%-67%) for CD20+ patients, and 43% (95% confidence interval 30%-54%) for CD20− patients (P = .15). Relapse did not differ between the groups. These results can serve as a reference to evaluate incorporation of anti-CD20 therapeutics to HSCT for the CD20+ acute lymphoblastic leukemia subset. Clinical trial numbers for www.clinicaltrials.gov are NCT00365287, NCT00305682, and NCT00303719.

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