Allogeneic hematopoietic stem cell transplantation for adult patients with t(4;11)(q21;q23) KMT2A/AFF1 B-cell precursor acute lymphoblastic leukemia in first complete remission: impact of pretransplant measurable residual disease (MRD) status. An analysis from the Acute Leukemia Working Party of the EBMT

Leukemia ◽  
2021 ◽  
Author(s):  
Jordi Esteve ◽  
Sebastian Giebel ◽  
Myriam Labopin ◽  
Tomasz Czerw ◽  
Depei Wu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Working Party ◽  
Cell Precursor ◽  
Hematopoietic Stem ◽  
Measurable Residual Disease ◽  
First Complete Remission

Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Patients With Acute Lymphoblastic Leukemia: No Difference in Related Compared With Unrelated Transplant in First Complete Remission

2004 ◽  
Vol 22 (14) ◽  
pp. 2816-2825 ◽  
Author(s):  
Michael G. Kiehl ◽  
Ludwig Kraut ◽  
Rainer Schwerdtfeger ◽  
Bernd Hertenstein ◽  
Mats Remberger ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
First Complete Remission

Purpose The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. Patients and Methods The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen–identical related (n = 103), or matched unrelated (n = 118) donor. Results Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P = .014) or who relapsed (P < .001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P = .052), and Philadelphia chromosome–positive patients had no poorer outcome than Philadelphia chromosome–negative patients. Total-body irradiation–based conditioning improved DFS in comparison with busulfan (P = .041). Conclusion Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.

scholarly journals Chemotherapy with the Use of TKIs Based on MRD Has the Potential to Avoid Hematopoietic Stem Cell Transplantation in Treatment for Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL). Results of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study ALL-Ph13

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3394-3394
Author(s):  
Atsushi Sato ◽  
Hirohide Kawasaki ◽  
Takao Deguchi ◽  
Yoshiko Hashii ◽  
Yuka Iijima-Yamashita ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Adverse Events ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
Fatal Adverse Events ◽  
First Complete Remission

Abstract Aims: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients generally have a poor prognosis when treated with chemotherapy alone. In adults, allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission is still the standard strategy for Ph+ALL. However, in children, HSCT should be avoided as much as possible to eliminate late complications. There are some reports showing that the combination of tyrosine kinase inhibitors (TKIs) with chemotherapy may avoid HSCT in childhood Ph+ALL. Thus, we planned this clinical trial (JPLSG ALL-Ph13) with the aim of improving outcomes with as few HSCT by chemotherapy with TKIs based on Ig/TCR minimal residual disease (MRD). Methods: Patients aged 1 to 19 with Ph+ALL were enrolled in JPLSG ALL-Ph13 Study. The diagnosis of Ph+ALL was performed using reverse-transcription PCR for BCR-ABL1. Chemotherapy follows the BFM ALL high-risk regimen (IA, IB, HR3, HR2, HR1, III, IM, III, IM, III, and maintenance). Imatinib was started on day 15 of induction therapy and continued until the final day of maintenance therapy (Ima group). If Ig/TCR MRD was positive (≥10 -4) at the end of IB, imatinib was changed to dasatinib and chemotherapy was continued (Dasa group). If MRD was positive at the end of the HR blocks, HSCT was performed (HSCT group). Results: During the period 2013-17, 43 patients were registered in this study, and 2 patients were excluded by not meeting inclusion criteria. Thirty-three, 7, and 1 patient were stratified into Ima, Dasa, and HSCT groups, respectively. Induction rate was 52.6% at the end of IA and 89.2% at the end of IB. MRD-negative rate was 61.3% at the end of IB and 87% at the end of HR. Although 51.2% of patients eventually received HSCT, only 13.9% received HSCT at the first complete remission. In all patients, the 3-year event-free survival (EFS) rate was 65.1%, and the 3-year overall survival (OS) rate was 85.1%. Four patients died of serious infections during treatment (2 in IA, 2 in 1st III). Interpretation: In our previous study for children with Ph+ALL (the JPLSG Ph+ALL04 study), all patients underwent HSCT, with the 3-year EFS rate of 57% and the OS rate of 80%. In this ALL-Ph13 study, the EFS and OS are almost the same as those in the Ph+ALL04. These are also almost the same as those in the EsPhALL2010 study, which aimed at avoiding HSCT. However, as in the EsPhALL2010 study, the comparatively high incidence of fatal adverse events was a problem with this study. Conclusion: Chemotherapy with the use of TKIs based on MRD has the potential to avoid HSCT in treatment for children with Ph+ALL. Reducing the occurrence of fatal adverse events is a future challenge to overcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation, Especially Haploidentical, May Improve Long-term Survival for Children With High-risk T-cell Acute Lymphoblastic Leukemia in First Complete Remission

2021 ◽  
Author(s):  
Yongzhan Zhang ◽  
Lu Bai ◽  
Xiao-jun Huang ◽  
Ai-dong Lu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Cell Acute Lymphoblastic Leukemia ◽  
First Complete Remission

Abstract Purpose The role of hematopoietic stem cell transplantation (HSCT) for children with high-risk (HR) T- cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under critical discussion. This study explored the hierarchical criteria, prognostic factors of childhood T-ALL, and the role of HSCT, especially haplo-HSCT, for children with HR T-ALL in CR1. Methods Seventy-four pediatric T-ALL patients were included in this study and stratified into low-risk chemotherapy cohort (n=16), high-risk chemotherapy cohort (n=31) and high-risk transplant cohort (n=24). Results Patient prognosis in the high-risk chemotherapy cohort was significantly inferior to the low-risk chemotherapy cohort (5-year overall survival (OS): 51.2%±10% vs. 100%, P = 0.003; 5-year event-free survival (EFS): 48.4%±9.8% vs. 93.8%±6.1%, P = 0.01; 5-year cumulative incidence of relapse (CIR): 45.5%±0.8% vs. 6.3%±0.4%, P = 0.043). The 5-year OS, EFS, and CIR of the high-risk transplant cohort were 77.0%±8.3%, 77.0%±8.3%, and 11.9%±0.4%, respectively. When compared to the high-risk chemotherapy cohort, the P values were 0.084, 0.041, and 0.011, respectively. Minimal residual disease (MRD) re-emergence, initial white blood cell (WBC) count, and age≥10 years were independent risk factors for prognosis. ConclusionsHSCT, especially haplo-HSCT, might effectively improve the survival outcomes for HR childhood T-ALL in CR1.

scholarly journals Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia

Blood ◽  
2018 ◽  
Vol 131 (14) ◽  
pp. 1522-1531 ◽  
Author(s):  
Nicola Gökbuget ◽  
Hervé Dombret ◽  
Massimiliano Bonifacio ◽  
Albrecht Reichle ◽  
Carlos Graux ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
Hematopoietic Stem ◽  
Grade 3 ◽  
Minimal Residual

Abstract Approximately 30% to 50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission after multiagent therapy exhibit minimal residual disease (MRD) by reverse transcriptase–polymerase chain reaction or flow cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label, single-arm study, adults with B-cell precursor ALL in hematologic complete remission with MRD (≥10−3) received blinatumomab 15 µg/m2 per day by continuous IV infusion for up to 4 cycles. Patients could undergo allogeneic hematopoietic stem-cell transplantation any time after cycle 1. The primary end point was complete MRD response status after 1 cycle of blinatumomab. One hundred sixteen patients received blinatumomab. Eighty-eight (78%) of 113 evaluable patients achieved a complete MRD response. In the subgroup of 110 patients with Ph-negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free survival (RFS) at 18 months was 54%. Median overall survival (OS) was 36.5 months. In landmark analyses, complete MRD responders had longer RFS (23.6 vs 5.7 months; P = .002) and OS (38.9 vs 12.5 months; P = .002) compared with MRD nonresponders. Adverse events were consistent with previous studies of blinatumomab. Twelve (10%) and 3 patients (3%) had grade 3 or 4 neurologic events, respectively. Four patients (3%) had cytokine release syndrome grade 1, n = 2; grade 3, n = 2), all during cycle 1. After treatment with blinatumomab in a population of patients with MRD-positive B-cell precursor ALL, a majority achieved a complete MRD response, which was associated with significantly longer RFS and OS compared with MRD nonresponders. This study is registered at www.clinicaltrials.gov as #NCT01207388.

Haploidentical Hematopoietic Stem Cell Transplant Compared with Matched Sibling and Unrelated Transplants in Adults with Philadelphia-Negative Acute Lymphoblastic Leukemia in First Complete Remission

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2299-2299 ◽  
Author(s):  
Qifa Liu ◽  
Lijie Han ◽  
Zhiping Fan ◽  
Fen Huang ◽  
Xuan LI ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Hematopoietic Stem Cell ◽  
Natural Science ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Matched Sibling ◽  
First Complete Remission

Abstract Matched-sibling donor (MSD) and matched unrelated donors (MUD) hematopoietic stem-cell transplantation (HSCT) have been recommended for the adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1). However, it is not defined for this portion of patients whether HLA haploidentical donor (HID) transplants can achieve equivalent outcomes compared to MSD and MUD transplants. From 2009 to 2014, 379 adult patients with Ph-negative ALL in CR1 underwent HID HSCT (n = 159), or MSD HSCT (n = 135), or MUD HSCT (n = 85). Among HID, MSD and MUD transplants, the 100-day incidences of acute graft-versus-host disease (aGVHD) Grade Ⅲ-IV were 11.0%, 8.4% and 10.6% respectively (P>0.05), and 2-year chronic GVHD (cGVHD) were 38.9%, 28.5% and 35.6% respectively ( P>0.05 ). At 5 years, the incidences of relapse were 19.0%, 24.0% and 23.4% in HID, MSD and MUD transplants respectively (P>0.05). The 5-year transplant related mortality (TRM) of HID was higher than MSD transplants (16.5% vs 10.9%, P = 0.032), and no difference compared with MUD transplants (16.5% vs 18.1%, P > 0.05). However, the 5-year overall survival (OS), disease-free survival (DFS) did not differ among HID, MSD and MUD transplants (OS 70.9%, 72.0%, 65.4% respectively, P > 0.05; DFS 67.3%, 66.0%, 62.0%, respectively, P > 0.05). Our results indicate that outcomes of adult patients with Ph-negative ALL in CR1 from HID transplants are comparable to MSD and MUD transplants. Disclosures Lin: National Natural Science Foundation of China 81400141: Research Funding; National Natural Science Foundation of China 81270647: Research Funding; Science and technology planning project of Guangdong Province 2014B020226004: Research Funding; The project of health collaborative innovation of Guangzhou City 201400000003-4: Research Funding.

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