BackgroundThe monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR) has become important to assess minimal residual disease (MRD) and standard of care in the treatment of chronic myeloid leukemia (CML). In this study, we performed a prospective, sequential analysis using RT-qPCR monitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP) who achieved complete cytogenetic remission (CCyR) and major molecular remission (MMR) throughout imatinib treatment.MethodsThe absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive. Sequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard protocols.ResultsBased on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories: (A) 57 (62.6%) had no variation on sequential analysis; (B) 30 (32.9%) had a single positive variation result obtained in a single sample; and (C) 4 (4.39%) had variations of BCR-ABL transcripts in at least two consecutive samples. Of the 34 patients who had elevated levels of transcripts (group B and C), 19 (55.8%) had a < 1% of BCR-ABL/BCR ratio, 13 (38.2%) patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations in Ph-negative cells were observed in five (5.5%) patients, and none of whom lost CCyR.ConclusionsDespite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent failure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of imatinib on the basis of BCR-ABL/BCR% sustained increase and mutational studies is a prudent approach for preserving other therapeutic options in imatinib-resistant patients.

Here we compare the management and survival outcomes of chronic myeloid leukemia (CML) patients who had early or late imatinib mesylate (IM) therapy. The cytogenetic and molecular responses of 189 CML patients were analyzed. Of this group, 121 patients were classified as the early chronic phase (ECP) group and started IM within 12 months of diagnosis. The other 68 patients were classified as the late chronic phase (LCP) group who had been treated with interferon (IFN)-alpha-2 and crossed over to IM more than 12 months after diagnosis. The overall rates of complete cytogenetic response (CCyR) and major molecular response (MMR) at last follow-up were 83.6 and 78.1% in the ECP and LCP groups, respectively. The CCyR rates were 89.3 (for ECP patients) versus 73.5% (for LCP patients; p < 0.0001). At last follow-up, 82.4% ECP and 64.2% LCP patients had achieved an MMR (p < 0.0001). No significant differences were noted between the two groups with regard to survival outcomes. Our experience reveals that IM is an effective rescue therapy in most CML LCP patients who are intolerant or in whom IFN-alpha therapy fails. Such therapeutic options should be considered in LCP patients, particularly in countries where IM may not be available.

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Donor lymphocyte infusion, a rescue therapy after hematopoietic stem cell transplantation, has been increasingly adopted, as modalities of stem cell transplantation have widened. First described as donor lymphocyte transfusion or cell therapy, it consists of infusion of donor lymphocytes, collected in steady state or after growth factor enhancement. As in literature the most used name is donor lymphocyte infusion, we'll adopt it here. Its most striking efficacy is observed in patients with chronic myelogenous leukemia, who relapsed after allogeneic stem cells transplantation. However, graft-versus-host disease, its main complication, may still hamper its feasibility. KEYWORDSAllogeneic hematopoietic stem cell transplantation (HSCT) has become an attractive approach for the treatment of many patients with hematological diseases, including malignant and nonmalignant disorders. Importantly, in the last 15 years, with the advent of reduced intensity conditioning (RIC) regimens, many older adult patients, initially excluded from this therapy approach, became eligible for HSCT. This approach decreased the transplant-related mortality, still maintaining T-cell immune response from the graft against the host tumor cells, also known as the graft-versus tumor or graft Practice points• Donor lymphocyte infusion (DLI) is an alternative strategy to reverse mixed chimerism, treat relapse and reconstitute immunity against infections after hematopoietic stem cell transplantation.• Responses to DLI are disease-dependent.• As main side effect, DLI can promote graft-versus-host disease (GVHD) in the range of 40-60% of patients.• The incidence of GVHD after unrelated DLI is similar to the incidence after related DLI, both presenting same pattern of presentation.• Although GVHD and graft versus leukemia (GVL) after DLI are highly correlated, some patients experience remission (GVL) without expressing GVHD.• Escalating doses for DLI is preferable, as it induces less GVHD. There is no clear association, yet confirmed, between T-cell dose and incidence of neither GVHD nor GVL after DLI.• The further DLI is made from transplantation, the better outcome.• Preadjuvant treatment before DLI is preferable as DLI effect is enhanced with low tumor burden.• Some strategies still under investigation are focused on separating GVHD and GVL, including graft engineering and gene therapy, to improve clinical outcome.For reprint orders, please contact: reprints@futuremedicine.com