Imatinib In Chronic Myeloid Leukemia Research Articles

Response to Therapy with Imatinib Mesylate in Patients with CML Is Poor in Non-Caucasian Patients.

Imatinib mesylate is a targeted therapy for chronic myeloid leukemia (CML). All phases of CML are susceptible to imatinib, with more durable responses occurring in patients in chronic phase. Studies in patients with chronic phase CML who have been treated with imatinib have shown a complete hematologic remission (CHR) rate of 97%, a complete cytogenetic remission (CCR) rate of 70%, and a complete molecular remission (CMR) rate of 10%. Racial and ethnic differences have not been extensively studied in relation to cancer outcomes, and no studies to date have demonstrated a difference in outcomes based upon race or ethnicity of patients with CML treated with imatinib.Methods: A retrospective chart review of patients with CML who have been treated with imatinib at the University of Illinois, the Westside VA, and MacNeal hospitals over the past 3 years was performed. Primary endpoints were rates of CHR, CCR, and CMR in Caucasian (C) and non-Caucasian (NC) patients with CML on treatment with imatinib. A secondary endpoint was the correlation of Sokal scores at initiation of imatinib with rates of CHR, CCR, and CMR.Results: 26 charts were reviewed of 7 C and 19 NC patients ( 12 African American, 5 Latino, 1 Indian, 1 Lebanese) in chronic phase CML. For C patients at the initiation of imatinib, mean age was 46 (45 for NC) and mean Sokal score was 0.79 (0.75 for NC). 32% (8/25) of patients had cytogenetic abnormalities in addition to the Philadelphia chromosome, all of whom were NC (50% were pretreated; 29% obtained CCR). Mean duration from diagnosis to treatment with imatinib was 5 months for C and 9 months for NC. Mean length of follow up while on imatinib was 28 months for C and 14 months for NC, with early termination due to lack of follow up, progression of disease, and death. 31% (8/26) of patients (25% C, 75% NC) had received prior treatments with agents such as IFN, AraC, busulfan, anagrelide, homoharrington, and allogeneic SCT. 100% of pretreated C had CCR (vs 33% of pretreated NC). CHR rate was 100% in C (4/4) vs. 87.5% (14/16) in NC. CCR was obtained in 100% of C (6/6) but only 14% (2/14) of NC. CMR rate was noted to be 33% (1/3) in Caucasians compared to 8.3% (1/12) in NC. Low risk Sokal scores were associated with CHR rate of 100% in C (3/3) and 75% (6/8) in NC, as well as CCR rate of 100% in C (5/5) and only 25% (2/8) in NC.Conclusions: NC patients have a poorer response to treatment with imatinib for CML. The discrepancy between complete response rates (most notably the CCR rate) between C and NC patients could be accounted for by differences in the genetic characteristics of the disease, metabolism, or adherence rates. NC patients with low risk Sokal scores also had poorer complete response rates than C patients with the same risk scores. Prospective studies are needed to further evaluate these differences and discern their etiology. Given poor CCR rates, NC patients should be HLA typed soon after diagnosis and considered for transplant if a matched donor is available.

Riddle: what do aplastic anemia, acute promyelocytic leukemia, and chronic myeloid leukemia have in common?

Secondary myelodysplastic syndrome (MDS)/acute leukemia frequently evolves from severe aplastic anemia (SAA) following immunosuppressive therapy. Secondary clonal cytogenetic abnormalities have now been reported after noncytotoxic therapy in two additional settings: all trans retinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL) and imatinib for chronic myeloid leukemia (CML). We propose that SAA, APL, CML, and MDS represent different manifestations of generalized insults to the bone marrow. In SAA, the insult to hematopoietic progenitors leads to an immune attack, while in APL, CML, and MDS, it gives rise to the malignant clones. A primary insult to bone marrow could simultaneously lead to several abnormal hematopoietic cell clones, with one dominating and the others present but below the level of detection. Such a 'field leukemogenic effect' would be analogous to the 'field cancerization effect' described in solid tumors. Nonspecific cytotoxic therapies, including antileukemic chemotherapy and allogeneic transplantation, have broad activity that could inhibit both the overt disease and other undetectable coexistent abnormal clones. In contrast, disease-specific targeted therapy such as immunosuppressive therapy in aplastic anemia, ATRA in APL, or imatinib in CML would have no activity against other abnormal clones, allowing them to expand and become detectable as the dominant clone declines.

Clinical results with imatinib in chronic myeloid leukaemia

Since its introduction 5 years ago, imatinib mesylate has shown remarkable efficacy in treating patients with chronic myeloid leukaemia. Here we shall review the clinical results seen with imatinib at all stages of the disease, current views on the best way to monitor patients’ responses and potential ways of predicting response to treatment. We shall also briefly cover the reasons why quiescent stem cells pose a theoretical threat to successful treatment.

Gynaecomastia in men with chronic myeloid leukaemia after imatinib

cKit and platelet-derived growth-factor receptor (PDGFR) are receptor tyrosine kinases expressed in the testis, are involved in testosterone production, and are inhibited by imatinib. We measured hormone concentrations in 38 men receiving imatinib for chronic myeloid leukaemia at baseline and during treatment. Mean follow-up was 23.6 months (SD 7.5). We noted seven cases of gynaecomastia (18%, 95% CI 6-30%). A comparison of hormone concentrations in 21 patients before and during treatment showed that patients who developed gynaecomastia had a reduction in free testosterone concentrations of 29.53 pmol/L (95% CI 11.63-47.43), while patients who did not had a decrease of 6.36 pmol/L (-1.02 to 13.74). In most men with chronic myeloid leukaemia studied here, imatinib was associated with a reduction in the production of testicular hormones and in some, with the development of gynaecomastia.