1,721,212 research outputs found
Advances in pharmacotherapy for myelofibrosis: what is the current state of play?
No full textIntroductionThe introduction of the first JAK inhibitor (JAKi) ruxolitinib 10 years ago represented a pivotal advancement in myelofibrosis (MF) treatment, mostly in terms of spleen and symptoms response. Nowadays three more JAKi, fedratinib, pacritinib, and momelotinib, are available for both ruxolitinib-resistant and na & iuml;ve patients. Moreover, many drugs are currently being investigated, both alone and in combination with JAKi.Areas coveredIn this review we discuss the long-term data of ruxolitinib and more recent evidence coming from clinical trials of fedratinib, pacritinib, and momelotinib, used as first- or second-line MF therapy. More, focus is set on data from non-JAKi drugs, such as the quite extensively studied BET-inhibitors (pelabresib) and BCL-inhibitors (navitoclax), novel target therapies, and drugs aimed to improve anemia, still representing a major determinant of reduced survival in MF.Expert opinionIt's now evident that JAKi monotherapy, though clinically effective, is rarely able to change MF natural history; novel drugs are promising but long-term data are inevitably lacking. We feel that soon MF treatment will require clinicians to select the most appropriate JAKi inhibitor, based on patient characteristics, associating either front-line or in case of early suboptimal response, non-JAKi drugs with the aim to pursue disease modification
Tyrosine kinase inhibitors for elderly chronic myeloid leukemia patients: a systematic review of efficacy and safety data
No full textPlasma cell leukemia occurring in a patient with thrombocythemia treated with hydroxyurea and busulphan
No full textReduced expression of cell cycle-associated genes in B lymphocytes purified from the peripheral blood of early-stage B chronic lymphocytic leukaemia patients.
No full textEUTOS score predicts early optimal response to imatinib according to the revised 2013 ELN recommendations.
No full textAbdominal abscess and Hafnia alvei septicemia occurring during the aplastic phase after autologous stem-cell transplantation in a patient with diffuse large B-cell lymphoma.
No full textHafnia alvei is a motile gram-negative bacterium that is rarely isolated from human specimens, but that sometimes can be found as part of the gastrointestinal flora. Here we report a rare case of Hafnia alvei septicemia with an abdominal abscess in a 60-year-old woman with diffuse large B-cell lymphoma involving the spleen, liver, and then lymph nodes. She initially received a splenectomy, and, over a 2-year period, four courses of chemotherapy. After achieving complete remission status, she underwent autologous peripheral blood stem-cell transplantation (PBSCT). During the aplastic phase following transplantation, the patient developed fever, diarrhea, and abdominal pain, with blood cultures positive for Hafnia alvei and an abscess in the splenic recess. Considering the high surgical risk, the infection was treated, successfully, with antibiotics (imipenem/cilastatin), without surgery or computed tomography (CT)-guided percutaneous drainage. Infections due to Hafnia alvei are rare, and this is the first reported case of Hafnia alvei septicemia in an adult hematologic patient undergoing a stem-cell transplantation procedure
How could patient reported outcomes improve patient management in chronic myeloid leukemia?
Full text linkIntroduction: Patients reported outcome (PRO) are still under-used in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), though data on the correlation between quality of life (QoL) and therapeutic efficacy are increasingly known. Chronic low-grade toxicities can reduce patient's QoL and negatively impact on adherence.Areas covered: This review will focus on the role of QoL questionnaires in patients with CML, receiving imatinib or newer TKIs (dasatinib, nilotinib, bosutinib, ponatinib). Physicians tend to underestimate the impact of TKI-related symptoms, in particular fatigue, that negatively affect QoL and can be a reason of poor adherence to therapy, with detrimental effect on long-term response. Few studies pointed out the role of PRO in CML, and there is paucity of questionnaires specifically designed for CML patients.Expert commentary: We recommend a wider use of PRO to join the pursuit of a rapid and deep responses with an optimization of QoL
The significance of early warning in chronic myeloid leukemia
Full text linkWe have read with great interest the manuscript by Eskazan and colleagues entitled “Critical appraisal of European LeukemiaNet (ELN) 2013 recommendations for the management of chronic myeloid leukemia: is it early for a warning?”. After a revision of the relatively limited literature, the Authors conclude that there are still no solid data to suggest a switch of therapy in patients with warning signs and that long-term survival remains a highly significant endpoint in CML patients. While we generally agree with these thoughts, we would like to stress a couple of additional points on the issue of ELN 2013 – defined “warning”. The ELN recommendations defines warning as less than partial cytogenetic response (PCyR) and/or BCR-ABL1 >10% (according to the International Scale – IS) at 3 months, less than complete cytogenetic response (CCyR) and/or BCR-ABL1 >1%IS at 6 months, and BCR-ABL1 >0.1% IS, i.e. no major molecular response (MMR) at 12 months. So, at the first two time-points, conventionally considered as “early”, both cytogenetic and molecular status define response, while at 12 months only BCR-ABL1 level >0.1 to 1%IS identifies warning patients, as anything less than CCyR is regarded as a failure. Our group analyzed the outcome of 216 CML patients treated with front-line standard dose (400 mg/day) imatinib with discordant cytogenetic and molecular responses at 3 and 6 months. Patients with even a single warning sign at 3 months (i.e. no PCyR or BCR-ABL1 >10%IS) had a significantly lower chance to obtain a subsequent CCyR (37% compared to 85% in patients with concordant optimal cytogenetic and molecular responses) and worse failure-free survival (FFS) (39% vs 81% at 48 months). Similarly, a warning sign at 6 months identified patients less prone to attain a MMR at 12 months (17% vs 82% in concordantly optimal patients) and with worse FFS (62% vs 88%). In our experience, most discordant patients had a “molecular warning”, as 15/17 discordant at 3 months were in PCyR or better but with BCR-ABL1 transcript >10%IS and at 6 months 20/25 discordant were in CCyR with BCR-ABL1 >1%IS. This finding is an indirect confirmation of the importance of a BCR-ABL1 transcript level <10%IS at 3 months (now defined “early molecular response”, EMR) as a positive predictor of long-term outcome, as reported by different studies. Despite EMR is gaining ground as a factor for an early switch of therapy, as suggested by NCCN guidelines, some reports indicate, in line with ELN recommendations, to consider also the 6-month cytogenetic or molecular status to assess a two-point evaluation of response to TKI therapy. The MDACC group analyzed the outcome of 453 CML patients treated with different TKIs, finding that 19 out of 44 patients (43%) not achieving major (i.e. optimal) cytogenetic response (MCyR) at 3 months obtained this response at 6 months and had an outcome comparable to patients achieving an earlier MCyR [8]. A Canadian study reviewed 320 patients receiving imatinib therapy with 3 and 6 month BCR-ABL1 transcript levels available, reporting that patients not achieving an EMR at 3 months but with BCR-ABL1 transcript <1% at 6 months (n=18) had similar FFS, progression-free survival (PFS) and overall survival (OS) compared to patients in EMR (n=184). Taken together, these data suggest that cytogenetic and molecular response at 6 months can identify a subgroup with favorable outcome among patients “warning” at 3 months. However, considering patients with cytogenetic and/or molecular warning at 3 months in our series (n=41), only 2 had a subsequent optimal cytogenetic and molecular response at 6 months (unpublished). Moreover, we found that the rates of warning responses at 3 and 6 months were higher in cases with b2a2 BCR-ABL1 transcript type compared to those with b3a2 variant (32% vs 24% at 3 months and 31% vs 12% at 6 months, respectively). If there is still debate on the practical significance of a warning at 3 or 6 months, even less consensus and significantly less data are about the meaning of a late (i.e. at 12 months) warning. Starting from their database of 483 patients treated with four different TKI strategies, colleagues at MDACC found no benefit, in term of survival, in patients achieving MMR while in CCyR, even if their landmark analysis was performed at 18 and 24 months, and not at the 12-months timepoint. A landmark analysis of PFS and OS on the bases of molecular response at 12 months of imatinib performed in 128 patients from our database did not find any difference between patients in MMR or not (personal data, unpublished). Concordantly, a Spanish group showed that, in 198 patients treated with standard-dose imatinib and in CCyR without MMR at 12 months, a switch to a second-generation TKI was associated with a higher probability of subsequently major and deep molecular response, but no advantage in terms of PFS and OS and higher rates of discontinuation for adverse events, compared to patients continuing imatinib. Hopefully, more information on the therapeutic approach to “warning” patients will come from an upcoming study of the GIMEMA Working Party on CML study aimed to evaluate efficacy of nilotinib frontline versus imatinib followed by switch to nilotinib in the case of absence of ELN-defined optimal response at 3, 6 or 12 months
Impact of fludarabine-based induction therapy on outcome of FLT3-/NPM1+ cytogenetically normal acute myeloid leukemia.
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