Effective use of imatinib-mesylate in the treatment of relapsed chronic myeloid leukemia after allogeneic transplantation
| Autor: | Sandra Irvine, Eibhlin Conneally, Mary Frances McMullin, Amjad Hayat, Stephen E. Langabeer, Shaun R. McCann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent medicine.medical_treatment Hematopoietic stem cell transplantation Gastroenterology Piperazines Hydroxycarbamide Young Adult hemic and lymphatic diseases Internal medicine Leukemia Myelogenous Chronic BCR-ABL Positive medicine Humans Transplantation Homologous Letter to the Editor GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) business.industry Hematopoietic Stem Cell Transplantation Hematology Administrative Staff Authors Middle Aged medicine.disease Transplantation Dasatinib Imatinib mesylate Pyrimidines Treatment Outcome Nilotinib Immunology Benzamides Imatinib Mesylate Female business Progressive disease Chronic myelogenous leukemia medicine.drug |
| Popis: | Despite recent advances in the treatment of chronic myeloid leukemia (CML), allogeneic stem-cell transplantation (SCT) remains the only curative option. The success of SCT is limited because of relapse in 20–30% of patients.1,2 As the graft-versus-leukemia (GvL) effect contributes to cure, the cessation of immunosuppression3 and use of donor lymphocyte infusions (DLI)4 have become established treatment for relapse. DLI is most effective if given for molecular or cytogenetic relapse. However, GvHD is increased if used in the first year post-transplant. Other options include interferon α(IFN) or a second transplant. Imatinib mesylate (IM) is a potent inhibitor of the BCR-ABL tyrosine kinase and achieves complete cytogenetic responses (CCR) in 87% of previously untreated patients.5 More recently its role in relapse after SCT has been highlighted.6,7 We describe the use of imatinib in 14 patients who relapsed post-SCT and were subsequently treated with IM. All patients with Ph-positive CML in first chronic phase (CP) who relapsed (n=14) following an allogeneic transplant performed between 1987 and 2004 are included. There were 7 males and 7 females. The median age at diagnosis was 31 years (range 15–48) (Table 1). Pre-transplant treatment included either hydroxycarbamide (OHU) and/or IFN. All patients were IM naive at the time of transplant and were transplanted in CP, 13 using a matched sibling donor and one a matched unrelated donor. Table 1. Pre-transplant. The conditioning regimen was Bu/Cy (9 patients) or Cy/TBI (5 patients). All the transplants were T-cell replete and cyclosporine and methotrexate were used as GvHD prophylaxis. Four patients developed acute GvHD limited to the skin and were treated with corticosteroids. Follow-up included clinical evaluation, blood counts, bone marrow examination including morphology and cytogenetics. From 2002, patients were monitored by qualitative, nested BCR-ABL RT-PCR and if positive, had BCR-ABL transcript levels determined by real-time quantitative PCR (RQ-PCR). Patients were deemed to have had a molecular relapse if greater than a five-fold increase in BCR-ABL transcript levels was observed. Median time to first relapse was 36 months (range 7–180) (Table 2). Prior to the availability of IM, 4 patients received DLI at incremental doses with only one patient showing any durable response. The other 3 patients proceeded to a reduced intensity-conditioning transplant with short responses before relapsing (Patients 2, 7 and 9 in Table 2). At the time of introduction of IM, 10 patients were in their first relapse and 4 patients were in second relapse. Four patients had a hematologic [3 CP and one accelerated phase (AP)] relapse, 4 had a cytogenetic relapse and the remaining 6 had a molecular relapse. Imatinib was started at a dose of 400 mg daily in all patients except the patient with AP disease who received 600 mg daily. Table 2. Post transplant. Thirteen (93%) patients responded to IM with a median time to response of four months (range 3–15). Of the 4 patients treated in hematologic relapse, 2 achieved a CCR and became nested PCR negative ( |
| Databáze: | OpenAIRE |
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