Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3547-3553 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge Cortes ◽  
Susan O'Brien ◽  
Francis J. Giles ◽  
Maher Albitar ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Response Rate ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Blast Phase ◽  
Molecular Abnormalities ◽  
Philadelphia Chromosome Positive

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor [Ph+, 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P = .001), longer median survival (7 versus 4 months, P = .04), and lower 4-week induction mortality (4% versus 15%, P = .07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

scholarly journals Outcome of patients with Philadelphia chromosome-positive chronic myelogenous leukemia post-imatinib mesylate failure

Cancer ◽  
2007 ◽  
Vol 109 (8) ◽  
pp. 1556-1560 ◽  
Author(s):  
Hagop Kantarjian ◽  
Susan O'Brien ◽  
Moshe Talpaz ◽  
Gautam Borthakur ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Philadelphia Chromosome Positive

Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome–positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge E. Cortes ◽  
Susan O'Brien ◽  
Francis Giles ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Interferon Α ◽  
Combination Regimens ◽  
Philadelphia Chromosome Positive

Abstract Fifty patients with Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML) in early chronic phase received imatinib mesylate, 400 mg orally daily. After a median follow-up of 9 months, 49 patients (98%) achieved a complete hematologic response and 45 patients (90%) achieved a major cytogenetic response, complete in 36 patients (72%). Compared with similar patients who received interferon-α with or without hydroxyurea or other interferon-α combination regimens, those receiving imatinib mesylate had higher incidences of complete and major (Ph < 35%) cytogenetic responses at 3 months (34% and 74% versus 1%-4% and 9%-24%, respectively), 6 months (52% and 80% versus 3%-7% and 11%-28%, respectively), and 9 months (60% and 77% versus 5%-11% and 14%-30%, respectively; P < .001). Competitive quantitative polymerase chain reaction (QPCR) studies at 9 months showed a median QPCR value (ratio of BCR-ABL/ABL transcripts × 100) of 0.59% overall and of 0.24% (range, 0.001%-29.5%) for complete cytogenetic response.

scholarly journals Effects of age on prognosis with imatinib mesylate therapy for patients with Philadelphia chromosome-positive chronic myelogenous leukemia

Cancer ◽  
2003 ◽  
Vol 98 (6) ◽  
pp. 1105-1113 ◽  
Author(s):  
Jorge Cortes ◽  
Moshe Talpaz ◽  
Susan O'Brien ◽  
Francis Giles ◽  
Mary Beth Rios ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Philadelphia Chromosome Positive

Response of Elevated Serum Soluble Interleukin-2 Receptor (sIL-2R) and Overexpression of Glucose-6-Phosphate Dehydrogenase (G6PD) in Patients with Chronic Myelogenous Leukemia Treated with Imatinib Mesylate.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4695-4695
Author(s):  
Eugene McPherson ◽  
M. Shanmughan ◽  
S.Y. Huang ◽  
J. Kleinfeld ◽  
E. Hazel ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Philadelphia Chromosome ◽  
Elevated Serum ◽  
Chronic Phase ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Cell Counts

Abstract Regulation of intracellular redox potential is important for regulation of cell growth. G6PD functions to catalyze the first step in the pentose phosphate pathway physiologically providing the NADPH required for reductive biosynthesis and detoxification of free-radicals and peroxides in mature red blood cells. We present two cases of patients (pts) with Chronic Myelogenous Leukemia-chronic phase (CML-cp) with significant overexpression of sIL-2R and G6PD. Serum elevated levels of sIL-2R and G6PD correlated to CML stage and response to therapy with imatinib; one male pt and one female pt with white blood cell counts of 80 and 21,000 X 109 per liter and a mean sIL-2R and G6PD levels of 26.975 X 103 pg/ml and 14.10 units/gHb respectively. Both pts had BCR/abl-RT-PCR positive gene rearrangements with b2a2 in peripheral blood and bone marrow. Chromosomal abnormalities of female pt was consistent with CML-cp (t 9; 22) ( q34;q11.2) philadelphia chromosome. Treatment of both pts with imatinib 400 mg orally daily resulted in reduction toward normal levels of sIL-2R and G6PD. Our female pt had to have therapy interrupted due to severe gastrointestinal and myelosuppression with cardiac irritation, edema, headaches and arthralgia. She was changed to 300 mg of imatinib with a proton-pump inhibitor, growth factor G-CSF, and a cox-2 inhibitor with excellent tolerance and response to therapy ( see table I). Response of sIL-2R and G6PD To Treatment With Imatinib Mesylate MONTHS LAP-SCORE sIL-2R (pg/ml) CRP (mg/dL) G6PD (units/gHb) LDH (U/L) Lap Score(NL 40-130); sIL-2R (NL 1,770-9,753); G6PD (3.5–5.0) Zero 4 26,975 16.0 11.1 386 Three 12 5,629 2.75 4.1 241 Six 17 12,868 0.75 3.6 266 Twelve 143 6,111 3.75 3.9 203 CONCLUSIONS: Overexpression of sIL-2R and G6PD in CML-cp pts treated with tyrosine kinase inhibitor imatinib mesylate were significantly reduced to levels within normal limits after twelve months of therapy. Peripheral blood sera sIL-2R and erythrocyte G6PD levels in CML-cp pts may be useful clinical and prognostic indicators of leukemic cell burden.

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