Marrow Transplantation for Chronic Myeloid Leukemia

Clift, Reginald A.

doi:10.1007/978-1-4615-2013-9_1

Cited by 24 publications

(20 citation statements)

References 90 publications

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“…Disease-free survival rates ranging from 20% to 40% at 4 years have been reported for patients meeting various definitions of CML in accelerated phase. [19][20][21][22][23][24] Because allogeneic transplantation is more often successful in patients with early rather than advanced CML, 25 clinical trials may be warranted to test whether preparative induction of response with imatinib improves the outcome of subsequent transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…[16][17][18] Allogeneic matched donor bone marrow transplantation (BMT) generally produces poor results in this patient population. 16,[19][20][21][22][23][24] Imatinib (Glivec [Gleevec in the United States; imatinib mesylate; Novartis Pharma AG]) is a rationally designed, potent selective competitive inhibitor of the Bcr-Abl protein-tyrosine kinase. [25][26][27][28] At therapeutic doses it also inhibits tyrosine kinase activity of the platelet-derived growth factor (PDGF) receptor ␤ and c-Kit, but does not affect other members of the type III receptor kinase family, such as Flt-3 and Fms.…”

Section: Introductionmentioning

confidence: 99%

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Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study

Talpaz

Silver

Druker

et al. 2002

Blood

915

575

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Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progressionfree and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity. (Blood. 2002;99:1928-1937

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study

Talpaz

Silver

Druker

et al. 2002

Blood

915

575

View full text Add to dashboard Cite

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“…Many patients undergo transplantation beyond the first year after diagnosis [4][5][6] and/or after they have progressed to an accelerated or blastic phase, [5][6][7] circumstances which compromise success rates. [4][5][6][7][8][9][10] Delay in transplantation often results from hesitancy by patients and treating physicians because of the early mortality associated with allogeneic marrow transplantation and controversy regarding its optimal timing. 11 Improved success rates would directly benefit patients undergoing this procedure and would likely extend its timely application to individuals who otherwise might delay or avoid transplantation.…”

mentioning

confidence: 99%

The influence of early transplantation, age, GVHD prevention regimen, and other factors on outcome of allogeneic transplantation for CML following BuCy

Copelan

Penza

Theil

et al. 2000

Bone Marrow Transplant

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Summary:Results in 164 patients who underwent allogeneic marrow transplantation following busulfan and cyclophosphamide over a 15 year period were analyzed. Age (median 37, range 14-66 years) did not significantly affect the incidence of graft-versus-host disease (GVHD), but patients who received methotrexate with cyclosporine had a significantly lower incidence (P = 0.002) of chronic GVHD compared to those who received methylprednisolone with cyclosporine. Hepatic veno-occlusive disease (VOD) occurred less frequently in chronic phase patients (P = 0.002) and in those transplanted shortly after diagnosis (P = 0.001). Five year leukemia-free survival (LFS) for the entire group was 49% (95% CI 41-57%). For 102 patients who underwent transplantation in chronic phase, results were significantly improved by transplantation at a short interval following diagnosis, particularly within 3 months (P = 0.01), by the use of methotrexate and not corticosteroids for GVHD prevention (P = 0.03), and by use of HLA-identical sibling donors (P = 0.01). Age was not a significant adverse prognostic factor and transplantation was successfully performed in individuals up to age 66. Allogeneic transplantation in CML, including older patients and those with unrelated donors, can be most safely and effectively performed shortly after diagnosis. Bone Marrow Transplantation (2000) 26, 1037-1043. Keywords: allogeneic transplantation; CML; BuCy Allogeneic marrow transplantation is the preferred treatment for 'young' patients with CML who have human leukocyte antigen (HLA)-identical sibling donors. However, because most individuals with CML are older than the 40 or 50 year threshold below which early transplantation is generally recommended 1-3 or lack histocompatible sibling donors, only a small proportion undergoes allogeneic mar-

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“…60 Por outro lado, os resultados para a doença na FA e CB são piores em consequência do aumento da mortalidade relacionada ao transplante (MRT) e da recidiva, que pode alcançar 50% ou mais. 61,62 Uma vantagem do TCTH é a sua capacidade de produzir uma resposta molecular completa que pode ocorrer em até 75% dos pacientes, e que está associada a um risco menor de recidiva e uma potencial cura da LMC. 14,64,65 Esta resposta molecular completa, entretanto, não é usual no tratamento com o mesilato de imatinibe (IM).…”

Section: Influência Dos Inibidores De Tirosina Quinase No Transplanteunclassified

Leucemia mieloide crônica e outras doenças mieloproliferativas crônicas

Funke¹,

Bitencourt²,

Vigorito³

et al. 2010

Rev. Bras. Hematol. Hemoter.

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Leucemia Mieloide Crônica: histórico, tratamento com inibidores de tirosino-quinase e recomendações da Leukemia NetOs primeiros casos de leucemia mieloide crônica (LMC) foram descritos em 1845. Em 1960 foi descrito o cromossomo Filadélfia (Ph), depois identificado como uma translocação recíproca entre os cromossomos 9 e 22. Em 1983, demonstrou-se que esta translocação justapõe a região BCR no cromossomo 22, ao gene c-ABL localizado no cromossomo 9, resultando num gene híbrido -o BCR-ABL. Em seguida verificou-se que o produto deste oncogene era uma proteína de 210 KD, com atividade de tirosina quinase. Em 1990, foi demonstrado em um modelo murino, que a presença do gene híbrido induzia uma doença mieloproliferativa semelhante à LMC vista em humanos, estabelecendo relação de causalidade entre o BCR-ABL e a LMC. 1,2 A irradiação corporal total ou esplênica, o uso de derivados de arsênico (licor de Fowley), o bussulfano e a hidroxiureia, tratamentos utilizados inicialmente, resultavam em controle hematológico, mas não havia mudança da histó-ria natural da doença, com uma inexorável progressão para

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Marrow Transplantation for Chronic Myeloid Leukemia

Cited by 24 publications

References 90 publications

Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study

Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study

The influence of early transplantation, age, GVHD prevention regimen, and other factors on outcome of allogeneic transplantation for CML following BuCy

Leucemia mieloide crônica e outras doenças mieloproliferativas crônicas

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