Measurable residual disease in chronic myeloid leukemia.

Chronic myeloid leukemia is characterized by a single genetic abnormality resulting in a fusion gene whose mRNA product is easily detected and quantified by reverse-transcriptase polymerase chain reaction analysis. Measuring residual disease was originally introduced to identify patients relapsing after allogeneic stem cell transplantation but rapidly adopted to quantify responses to tyrosine kinase inhibitors. Real-time quantitative polymerase chain reaction is now an essential tool for the management of patients and is used to influence treatment decisions. In this review we track this development including the international collaboration to standardize results, discuss the integration of molecular monitoring with other factors that affect patients' management, and describe emerging technology. Four case histories describe varying scenarios in which the accurate measurement of residual disease identified patients at risk of disease progression and allowed appropriate investigations and timely clinical intervention.Susan Branford, and Jane F. Apperle

Hematologic malignancies in pregnancy : Management guidelines from an international consensus meeting

Purpose: The incidence of hematologic malignancies during pregnancy is 0.02%. However, this figure is increasing, as women delay conception until a later age. Systemic symptoms attributed to the development of a hematologic cancermay overlapwith physiologic changes of pregnancy. A favorable prognosis is contingent upon early diagnosis and treatment. Therefore, a high index of suspicion is required by health care providers. Although timely, accurate diagnosis followed by appropriate staging is essential and should not be delayed due to pregnancy, management guidelines are lacking due to insufficient evidence-based research. Consequently, treatment is delayed, posing significant risks to maternal and fetal health, and potential pregnancy termination. This report provides guidelines for clinical management of hematologic cancers during the perinatal period, which were developed by a multidisciplinary team including an experienced hematologist/oncologist, a high-risk obstetrics specialist, a neonatologist, and experienced nurses, social workers, and psychologists. Methods: These guidelines were developed by experts in the field during the first International Consensus Meeting of PrenatalHematologicMalignancies, which took place in Leuven, Belgium, onMay 23, 2014. Results and Conclusion: This consensus summary equips health care professionals with novel diagnostic and treatment methodologies that aimfor optimal treatment of themother, while protecting fetal and pediatric health

Mesenchymal stromal cells for acute graft-versus-host disease: response at 1 week predicts probability of survival.

Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid-resistant graft-versus-host-disease (GvHD). However, the lack of early predictors of clinical responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients' overall survival. In our cohort, cell dose, patients' age and type of organ involvement are crucial factors associated with clinical responses

Oligoclonal reconstitution after high dose therapy with PBPCT in myeloma patients: Implications for assessment of remission status

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group.

We studied the clinical course of 130 chronic myeloid leukemia (CML) patients (89 males and 41 females) in the European Bone Marrow Transplantation Group (EBMT) registry who received transplants before January 1, 1988 and who subsequently had evidence of recurrent leukemia. All patients had received a pretransplant conditioning regimen including total body irradiation (TBI). The first evidence of relapse was cytogenetic only in 74 (57%) patients and hematologic in 56 (43%). The overall actuarial survival from relapse was 36% at 6 years, with a significantly higher proportion of survivors among female patients (53% v 30%; P < .002). In univariate analysis, the 6-year probability of survival was 52% for patients with cytogenetic relapse and 30% for patients relapsing in chronic phase (CP), while no patient who relapsed in advanced phase (AP or BC) survived more than 3.5 years from relapse (P < .0001). The actuarial survival of patients relapsing before 6 months, between 6 and 12 months, and later than 12 months after transplant was 27%, 26%, and 45%, respectively (P < .002). Among patients with cytogenetic relapse, partial or complete disappearance of Ph-positive cells occurred in 40% of untreated patients and in 42% of those treated with interferon (IFN). However, IFN therapy significantly delayed progression toward hematologic disease. Cytogenetic responses were observed in 25% of patients who received IFN for relapse into CP, while only one minor cytogenetic response was reported in patients on conventional chemotherapy. For patients presenting with cytogenetic relapse as well as for those in hematologic relapse, IFN therapy significantly improved the 2-year probability of survival. However, long-term survival for IFN-treated patients in either group was not different from long-term survival in comparable patients not receiving IFN therapy. Twenty-nine patients of this series underwent a second bone marrow transplant (BMT) and the projected survival at 4 years after the second transplant is 28%. In multivariate Cox regression analysis, four factors remained significantly associated with survival: disease phase at relapse (P < .0001), duration of time interval from BMT to relapse (P = .0001), interferon therapy at relapse (P = .0024), and patient sex (P = .0032). This retrospective study provides evidence that some patients who relapse after BMT may benefit from treatment with IFN; a second BMT may offer the chance of cure. Data from this analysis may be useful in designing future prospective trials on posttransplant CML relapse

Primary plasma cell leukemia and autologous stem cell transplantation

Background Primary plasma cell leukemia is a rare disorder accounting for less than 5% of malignant plasma cell diseases. It has a poor prognosis compared to multiple myeloma, with a median survival of 8-12 months. The results of conventional therapy are disappointing though autologous stem cell transplantation may improve survival. Design and Methods A retrospective analysis was undertaken of the European Group for Blood and Marrow Transplantation experience of 272 patients with plasma cell leukemia and 20844 with multiple myeloma undergoing first autologous transplantation between 1980 and 2006. All patients were reported to the European Group for Blood and Marrow Transplantation registry using MED-A (limited data) or MED-B (extensive data) forms. All patients were included regardless of availability of complete data. Results There was no difference in type of graft or use of total body irradiation between patients with plasma cell leukemia and multiple myeloma, but the group with plasma cell leukemia was transplanted earlier after diagnosis (6.0 versus 7.7 months, P=0.000). Patients with plasma cell leukemia were more likely to enter complete remission after transplantation but their overall survival (25.7 months, 95% confidence interval 19.5-31.9 months) was inferior to that of patients with multiple myeloma (62.3 months, 95% confidence interval 60.4-64.3 months) (P=0.000), due to the short duration of their post-transplant response and increased non-relapse-related mortality. Conclusions This largest study ever reported on plasma cell leukemia suggests that autologous transplantation can improve outcome, although results are markedly inferior to those achieved in patients with multiple myeloma, highlighting the need for novel approaches to this aggressive disorder.Development and application of statistical models for medical scientific researc