scholarly journals PF190 PLASMA LEVELS AND OUTCOMES OF PROPHYLACTIC POST-TRANSPLANT PONATINIB ADMINISTRATION IN PATIENTS WITH PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (PH+ALL)

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 47
Author(s):  
S. Nanno ◽  
H. Okamura ◽  
M. Nakamae ◽  
A. Hirose ◽  
K. Matsumoto ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Plasma Levels ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Post Transplant ◽  
Philadelphia Chromosome Positive

Pharmacokinetics of Dasatinib in a Patient with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia During Treatment with Anti-Tuberculosis Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5006-5006
Author(s):  
Michelle P. Zeller ◽  
Jan H Beumer ◽  
Susan M Christner ◽  
Anargyros Xenocostas
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Plasma Levels ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Concomitant Treatment ◽  
Line Treatment ◽  
Apparent Clearance ◽  
Concentration Changes ◽  
Tuberculosis Therapy ◽  
Philadelphia Chromosome Positive

Abstract Abstract 5006 Objectives: Dasatinib is a second generation protein-tyrosine kinase inhibitor (TKI) indicated for first line treatment of chronic myeloid leukemia (CML) and second line treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) in patients who are imatinib resistant or intolerant. In this study, we present the case of a patient with Philadelphia chromosome- positive ALL, intolerant to imatinib, who developed reactivated tuberculosis (TB) while receiving dasatinib during maintenance chemotherapy. The purpose of our study was to determine the effects of concomitant anti-TB therapy on dasatinib exposure by measuring plasma dasatinib levels using three different oral doses of the drug in this patient. Methods: The patient was treated with isoniazid, rifampin, ethambutol, pyrazinamide and pyridoxine for 2 months, followed by isoniazid, rifampin and pyridoxine for an additional 4 months. Dasatinib therapy was continued at the initiation of TB therapy using 100 mg po od, and titrated by 50 mg increments to 200 mg po od. Dasatinib plasma levels were measured prior to initiating anti-TB treatment and at regular intervals during concomitant treatment using three different dasatinib doses. Results: Eight days after initiation of anti-tuberculosis therapy, the apparent clearance of dasatinib had increased from 1410 to 2174 L/h at 100 mg. However, at 150 mg and 200 mg doses, apparent clearance had decreased to levels lower than baseline. As expected, the direction of peak plasma concentration changes was inverse to the changes in apparent clearance: Cmax values were 30 at baseline, and 22, 46, 102 ng/mL for the 3 doses of dasatinib during anti-TB therapy, respectively. Conclusions: Our findings suggest dasatinib clearance is increased by approximately 50% shortly after initiating anti-tuberculosis treatment and increasing the dose of dasatinib during anti-TB therapy was able to restore dasatinib plasma levels to those observed before initiation of anti-TB therapy. (This work was supported by an unrestricted grant from Bristol Myers Squib) Disclosures: No relevant conflicts of interest to declare.

scholarly journals Pre-Emptive Tyrosine Kinase-Inhibitor Intervention Based on BCR/ABL1 Monitoring in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia after Allo-HSCT: Two Independent Observational Cohort Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3303-3303
Author(s):  
Liu Hui ◽  
Li Xuan ◽  
Ren Lin ◽  
Lan Deng ◽  
Fen Huang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tyrosine Kinase ◽  
Protective Factor ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Central Nervous System Relapse ◽  
Cell Transplant ◽  
Post Transplant ◽  
Philadelphia Chromosome Positive

Relapse is a major cause of treatment-failure in persons with Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph+ALL) receiving an allogeneic hematopoietic cell transplant. There is controversy whether post-transplant tyrosine kinase-inhibitors (TKIs) reduces relapse risk. We evaluated a pre-emptive strategy in 103 subjects in a prospective study with prophylactic group as historical control. Subjects were tested for measurable residual disease (MRD) by assaying levels of BCRABL1 transcript. MRD was considered positive if the levels of BCRABL1 transcript were >=10-5. Subjects with positive MRD post-transplant received TKI-therapy. The chosen of TKIs was based on BCRABL1 mutation, and donor lymphocyte infusion (DLI) was recommended in those who were not responsive to TKIs. The primary endpoint was relapse (including hematological relapse and central nervous system relapse). Twenty-three of 103 subjects were MRD-positive post-transplant. Seven of whom had BCRABL1 mutations including T315I (N=5). Pre-emptive therapy resulted in 21 subjects being MRD-test negative. The overall 3-year cumulative incidence of relapse (CIR) post-transplantation was 11% (95% confidence interval [CI], 4, 17%) and 34% (22,1, 46.5%) in the pre-emptive and prophylactic maintain group (P=0.030). The 3-year cumulative survival and LFS post-transplants in the pre-emptive and prophylactic group were 87% (80, 94%) and 63% (51, 75%), and 83% (76, 91%) and 58% (46, 70%) (P=0.000 and P=0.000, respectively). The multivariate analysis showed that positive MRD pre-transplantation was the risk factor for relapse, LFS and survival [HRs=8.977(3.344, 24.096; P=0.000), HRs=4.763 (2.153, 10.538; P=0.000) and HRs=7.535 (2.977,19.071; P=0.000], while pre-emptive therapy was the protective factor for relapse, LFS and survival [HRs=0.176 (0.077, 0.339; P=0.000), HRs=0.222 (0.107, 0.462; P=0.000) and HRs=0.188 (0.082,0.43; P=0.000)]. Our data suggest a pre-emptive strategy based on MRD-test monitoring and mutation analyses might reduce CIR and improve survival after allotransplants for Ph+ALL (NCT 01883219). Disclosures No relevant conflicts of interest to declare.

scholarly journals P190BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature

2021 ◽  
pp. 1040-1050
Author(s):  
Samah Kohla ◽  
Sarah EL Kourashy ◽  
Zafar Nawaz ◽  
Reda Youssef ◽  
Ahmad Al-Sabbagh ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Rare Case ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Cytogenetic Abnormality ◽  
Rare Case Report ◽  
Philadelphia Chromosome Positive

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 <i>BCR-ABL1</i>) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

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