What Does One do for the CML Patient in Relapse After Allogeneic Bone Marrow Transplantation?

Abstract

The management of CML patients with some evidence of disease after BMT depends on the molecular, cytogenetic and hematological findings of relapse. Presently, a number of technical and biological problems do not allow to draw any definitive conclusion on the prognostic significance of Minimal Residual Disease detected by PCR. A positive PCR, particularly if observed late after BMT, leads to increase the frequency of cytogenetic examinations, but a therapeutic intervention is not justified. The criteria to define the cytogenetic relapse are not still established. Therefore it is difficult to interpret the reappearance of Ph-1 chromosome after BMT as disease recurrence invariably progressing towards the hematological phase. However, alpha-Interferon, donor buffy-coat infusion or their association should be considered in the treatment of patients for whom the cytogenetic relapse has been confirmed. The therapeutic approach to patients with hematological relapse is mainly depending on the phase of disease. The single, sequential or combined use of chemotherapy, alpha-IFN, donor buffy-coat infusion and second transplant has been shown to be effective in restoring donor hematopoiesis in several patients who relapsed either in chronic or advanced phase. Prospective, randomized, multicentre trials on CML relapse after BMT should be planned.

Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes

“…4 These reports highlight were duration between BMT1 and relapse (or BMT2), situthe difficulties in treating leukemia relapse after BMT. The strategy to decrease relapse comprises three parts: prediction of high relapse risk 13 and reorganization of pre-BMT conditioning for this group, 14 prevention of relapse by reduction of invisible leukemia cells with induction of GVHD (GVL), and finally, prediction of minimal residual disease 15 and early treatment of MRD by biological response modifiers such as IFN␣, IL-2 and TNF.…”

“…After relapse, treatment of leukemia is very difficult ␣ resulted in 10-25% cytogenetic complete remission in but survival is very short (less than 6 months) without treatpatients with CML in CP. 4 Infusion of donor leukocytes ment. 3,12 Reinduction chemotherapy for acute leukemia is was also effective, but acute GVHD and bone marrow aplaeffective, and up to a 70% remission rate has been reported sia were common complications.…”

Expressão de microRNAs em células Bcr-Abl1 positivas: associação com a resistência à apoptose e fisiopatologia da Leucemia Mielóide Crônica

“…Devido sua alta morbi-mortalidade, o TMO limita-se àqueles pacientes com menos de 55 anos e que possuem doadores HLA compatíveis (GOLDMAN, 2001 e HEHLMANN et al, 2007). Em caso de recidiva da doença pós-TMO, os pacientes são submetidos à infusão de linfócitos do doador (donor lymphocyte infusion) no receptor que induz a remissão da doença em 80% dos casos, porém, alguns pacientes não respondem ao DLI(ARCESE et al, 1993;LEVENGA et al, 2007). As principais causas da resistência das células ao MI são: presença de mutações no sítio catalítico de Bcr-Abl, duplicação do cr Ph, superexpressão do gene bcr-abl1 e expulsão do fármaco pela célula leucêmica com elevado número de glicoproteína P na a expressão gênica (LAMY et al, 2006;SHIVDASANI et al, 2006;YU et al, 2006;ZHANG et al, 2006;VENTURINI et al, 2007)…”