scholarly journals Adults with Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia: Considerations for Allogeneic Hematopoietic Cell Transplantation in First Complete Remission

2019 ◽  
Vol 25 (2) ◽  
pp. e41-e45 ◽  
Author(s):  
Ibrahim Aldoss ◽  
Muhammad O. Kamal ◽  
Stephen J. Forman ◽  
Vinod Pullarkat
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
First Complete Remission

scholarly journals Superior survival with pediatric-style chemotherapy compared to myeloablative allogeneic hematopoietic cell transplantation in older adolescents and young adults with Ph-negative acute lymphoblastic leukemia in first complete remission: analysis from CALGB 10403 and the CIBMTR

Leukemia ◽  
2021 ◽  
Author(s):  
Matthew J. Wieduwilt ◽  
Wendy Stock ◽  
Anjali Advani ◽  
Selina Luger ◽  
Richard A. Larson ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct ◽  
First Complete Remission

AbstractOptimal post-remission therapy for adolescents and young adults (AYAs) with Ph-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is not established. We compared overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) for patients receiving post-remission therapy on CALGB 10403 to a cohort undergoing myeloablative (MA) allogeneic hematopoietic cell transplantation (HCT) in CR1. In univariate analysis, OS was superior with chemotherapy compared to MA allogeneic HCT (3-year OS 77% vs. 53%, P < 0.001). In multivariate analysis, allogeneic HCT showed inferior OS (HR 2.00, 95% CI 1.5–2.66, P < 0.001), inferior DFS (HR 1.62, 95% CI 1.25–2.12, P < 0.001), and increased NRM (HR 5.41, 95% CI 3.23–9.06, P < 0.001) compared to chemotherapy. A higher 5-year relapse incidence was seen with chemotherapy compared to allogeneic HCT (34% vs. 23%, P = 0.011). Obesity was independently associated with inferior OS (HR 2.17, 95% CI 1.63–2.89, P < 0.001), inferior DFS (HR 1.97, 95% CI 1.51–2.57, P < 0.001), increased relapse (1.84, 95% CI 1.31–2.59, P < 0.001), and increased NRM (HR 2.10, 95% CI 1.37–3.23, P < 0.001). For AYA ALL patients in CR1, post-remission therapy with pediatric-style chemotherapy is superior to MA allogeneic HCT for OS, DFS, and NRM.

Superiority of Pediatric Chemotherapy over Allogeneic Hematopoietic Cell Transplantation for Philadelphia Chromosome Negative Adult ALL in First Complete Remission: A Combined Analysis of Dana-Farber ALL Consortium and CIBMTR Cohorts

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 319-319
Author(s):  
Matthew D. Seftel ◽  
Donna Neuberg ◽  
Mei-Jie Zhang ◽  
Hai-Lin Wang ◽  
Julie Bergeron ◽  
...  
Keyword(s):  
Complete Remission ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Philadelphia Chromosome ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Allogeneic Hct ◽  
Unrelated Donors ◽  
First Complete Remission

Abstract Introduction: In adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL), the optimal post-remission therapy remains uncertain. Although allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR1) has become a widely adopted curative strategy, the need for HCT may be supplanted by intensive, pediatric-style chemotherapy regimens. These two approaches have not previously been compared. Methods: We evaluated the outcomes of 422 related or unrelated donor HCT recipients aged 18-50 years with Ph-ALL in CR1 between 06/2002 and 12/2011 as reported to the CIBMTR. This was compared to a concurrent cohort of 108 Ph- ALL CR1 pts (18-50 years) who received a Dana Farber Cancer Institute (DFCI) ALL Consortium pediatric regimen consisting of intensive, non-HCT therapy. Primary outcome was disease-free survival (DFS). Patients in the DFCI chemotherapy cohort who received HCT in CR1 were censored at the day of HCT. Left-truncated analysis methods were used to adjust time from CR1 to transplant. Results: The HCT cohort was older (median age 34 vs. 30 years, p=0.001) and had higher diagnostic WBC counts (median 12x109/L [range <1-515) vs. 8x109/L [1-1424], p=0.001, respectively). The proportion of patients with T –ALL was lower in the HCT cohort (14% vs. 22%, p=0.03), while the incidence of t(4;11)/MLL was similar in both groups (8% vs. 10%, respectively). Of the HCT cohort 396 (94%) underwent myeloablative (MA) conditioning. Donor source was matched related donor in 176 (42%), 8/8 unrelated donors in 168 (40%), and 7/8 (18%) from 7/8 unrelated donors. In univariate analyses (Figure 1) cumulative incidence of relapse at 4 years was similar in both groups (HCT 25% [19-28] vs. chemo 23% [15-32] p=0.97). Two-year treatment-related mortality (TRM) was higher in the HCT cohort (HCT 33% [28-39] vs. chemo 4% [1-8], p<0.0001). At 4 years, DFS was superior in the chemo cohort (HCT 40% [35-45] vs. chemo 71% [60-79], p<0.0001). Four year OS also favored chemo (HCT 45% [40-50] vs. chemo 73% [63-81], p<0.0001). In multivariable analysis, independent factors predictive of treatment failure (relapse or death) were HCT (HR 3.11 [2.08 – 4.66], p<0.001) and the presence of CNS disease at diagnosis (HR 1.56 [1.03 – 2.38], p=0.04). The sole factor associated with poorer OS was the administration of HCT (HR 2.86 [1.88 – 4.34], p<0.0001). The favorable OS with chemo was maintained when restricting the HCT cohort to those recipients with related donors or fully matched (8/8) unrelated donors and those whose time from diagnosis to CR1 was <8 weeks (HR 2.14 [1.36-3.35], p=0.001). Similar outcomes were seen when restricting the HCT cohort to those who achieved CR1 < 8 weeks from diagnosis and received myeloablative conditioning. Conclusion: In this comparison of two cohorts of younger Ph- negative adults in CR1, post-remission therapy with an intensive, pediatric-inspired, chemotherapy-based regimen conferred a survival advantage when compared to allogeneic HCT. The high TRM associated with HCT is a major factor in determining outcomes after HCT. In an era of increasing adoption of pediatric regimens for adults with Ph- ALL, allogeneic HCT may no longer be required for the majority of patients who achieve CR1. These data support the need for randomized controlled studies in Ph- ALL comparing pediatric-inspired non-HCT regimens to allogeneic HCT-based therapy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document