scholarly journals Prevalence of atypical BCR-ABL1 transcript types in adult Philadelphia chromosome-positive acute lymphoblastic leukemia: implications for measurable residual disease

2021 ◽  
Author(s):  
Úna Bhreathnach ◽  
Laura Kearney ◽  
Stephen E. Langabeer
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Measurable Residual Disease ◽  
Philadelphia Chromosome Positive

scholarly journals Phase 2 study of pembrolizumab for measurable residual disease in adults with acute lymphoblastic leukemia

2020 ◽  
Vol 4 (14) ◽  
pp. 3239-3245
Author(s):  
Ryan D. Cassaday ◽  
Kelsey-Leigh A. Garcia ◽  
Jonathan R. Fromm ◽  
Mary-Elizabeth M. Percival ◽  
Cameron J. Turtle ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Stevens Johnson Syndrome ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Measurable Residual Disease

Abstract The presence of measurable residual disease (MRD) in acute lymphoblastic leukemia (ALL) confers a poor prognosis. CD19-targeted immunotherapy is effective against MRD but is logistically challenging, potentially toxic, and not applicable to T-cell ALL. We thus hypothesized that inhibition of PD-1 with pembrolizumab could also be effective for MRD, but without lineage restriction. The primary objective of this phase 2 study was to evaluate the efficacy of pembrolizumab in patients with ALL and MRD. Key eligibility criteria included adults with B- or T-cell ALL and MRD detectable by multiparameter flow cytometry or quantitative polymerase chain reaction from bone marrow aspirate (BMA) despite chemotherapy (plus ABL kinase inhibitor if Philadelphia chromosome positive). Pembrolizumab 200 mg IV was given every 3 weeks. Response was assessed by BMA using methods that previously detected MRD. The primary end point was complete MRD response rate. We stopped enrollment early; only 1 of 12 (8%) experienced a complete MRD response, which lasted 3 weeks. Interestingly, this patient had previously received hematopoietic cell transplantation and CD19-targeted chimeric antigen receptor–modified T-cell therapy and was the only patient to experience an immune-related adverse event from pembrolizumab (grade 3 Stevens-Johnson syndrome). Median overall survival from enrollment was 12.7 months. In summary, pembrolizumab had minimal activity against MRD but was generally well tolerated. These data can be compared with ongoing anti-PD-1 combination studies in ALL, and they further establish the role of trials specifically for patients with MRD. This trial was registered at www.clinicaltrials.gov as #NCT02767934.

scholarly journals Dasatinib for a child with Philadelphia chromosome–positive acute lymphoblastic leukemia and persistently elevated minimal residual disease during imatinib therapy

2015 ◽  
Vol 22 (4) ◽  
pp. 303 ◽  
Author(s):  
K.H. Wu ◽  
H.P. Wu ◽  
T. Weng ◽  
C.T. Peng ◽  
Y.H Chao
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Intensive Chemotherapy ◽  
Molecular Remission ◽  
Allogeneic Hsct ◽  
Minimal Residual ◽  
Philadelphia Chromosome Positive

Imatinib has improved outcomes in patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (all). Minimal residual disease (mrd) is a useful tool for predicting leukemia relapse. However, there is no consensus on how to treat children with elevation of BCR-ABL transcripts but no evidence of hematologic relapse during chemotherapy combined with imatinib. Here, we report the case of a child with Ph+ all who had persistent elevation of mrd, but no evidence of hematologic relapse while receiving imatinib plus intensive chemotherapy. Dasatinib was substituted for imatinib because no suitable donor for allogeneic hematopoietic stem-cell transplantation (hsct) was available. Less-intensive chemotherapy with methotrexate and 6-mercaptopurine was administered concomitantly. No serious adverse events were encountered. With continuous dasatinib combined with chemotherapy, but no allogeneic hsct, our patient reached complete molecular remission and has been in complete molecular remission for more than 13 months. This report is the first about the long-term use of dasatinib in patients with Ph+ all and mrd elevation but hematologic remission during imatinib chemotherapy. In a similar situation, chemotherapy combined with dasatinib instead of allogeneic hsct could be considered to avoid hsct-related mortality and morbidity. Clinical trials are needed.

scholarly journals Monitoring Ponatinib in a Child with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

2021 ◽  
pp. 24-28
Author(s):  
Kazuki Tanimura ◽  
Kai Yamasaki ◽  
Yuki Okuhiro ◽  
Kota Hira ◽  
Chika Nitani ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitor ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prospective Trial ◽  
Philadelphia Chromosome ◽  
Therapeutic Drug ◽  
Optimal Dosage ◽  
Minimal Residual ◽  
Philadelphia Chromosome Positive

Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) reported to show a higher efficacy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) than other TKIs. However, few studies describe ponatinib for pediatric Ph+ALL; therefore, the efficacy, safety, and optimal dosage have not been determined. Here, we report a 3-year-old girl with Ph+ALL treated by a ponatinib-containing regimen with therapeutic drug monitoring in the plasma and cerebrospinal fluid (CSF). In our case, a ponatinib-containing regimen was able to keep minimal residual disease negative, and the pharmacokinetics (PKs) of plasma ponatinib resembled that previously reported in adults. Penetration to the CSF was extremely limited. Thus, ponatinib was feasible and effective for a child with Ph+ALL, although the plasma concentration of ponatinib varied significantly throughout the treatment. The appropriate dosage should be confirmed in a prospective trial, including a detailed PK study.

scholarly journals Dasatinib-based Two-step Induction for Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
Isamu Sugiura ◽  
Noriko Doki ◽  
Tomoko Hata ◽  
Ryuko Cho ◽  
Toshiro Ito ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
High Dose ◽  
Clinical Trial Registry ◽  
Hematopoietic Stem ◽  
Consolidation Phase ◽  
T315i Mutation ◽  
Philadelphia Chromosome Positive

The standard treatment for adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in Japan is imatinib-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, approximately 40% of patients cannot undergo HSCT in their first complete remission (CR1) because of chemotherapy-related toxicities and relapse before HSCT, and older age. We evaluated dasatinib-based two-step induction with the primary endpoint of 3-year event-free survival (EFS) in this study. The first induction (IND1) was dasatinib plus prednisolone to achieve CR and the second (IND2) was dasatinib plus intensive chemotherapy to achieve minimal residual disease (MRD)-negativity. Patients who achieved CR and had an appropriate donor were recommended to undergo HSCT during a consolidation phase later than the first consolidation, which included high-dose methotrexate. Prophylactic dasatinib after HSCT was assigned to patients with positive pre-transplant MRD. All 78 eligible patients achieved CR or incomplete CR after IND1, and 52.6% achieved MRD-negativity after IND2. Non-relapse mortality (NRM) was not reported. T315I mutation was detected in all 4 hematological relapses before HSCT. Fifty-eight (74.4%) patients underwent HSCT in CR1 and 44 (75.9%) were negative with pre-transplant MRD. At a median follow-up of 4.0 years, the 3-year EFS and overall survival were 66.2% (95% confidence interval [CI], 54.4-75.5) and 80.5% (95% CI, 69.7-87.7), respectively. The cumulative incidence of relapse and NRM at 3 years from enrollment were 26.1% and 7.8%, respectively. Dasatinib-based two-step induction was demonstrated to improve the 3-year EFS. This study was registered in the UMIN Clinical Trial Registry as #UMIN000012173.

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