How could patient reported outcomes improve patient management in chronic myeloid leukemia?

Introduction: 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

Feasibility and Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in 30 Patients with Poor Risk Acute Myeloid Leukemia Older than 60 Years

We report on the feasibility and outcome of allogeneic SCT (allo-SCT) in 30 poor risk AML patients older than 60 years. Median age at transplant was 63 years (range 60-70 years) and 18/30 (60%) cases were in complete remission. Donors were MUD in 40% and sibling in 60% of cases. Twenty-six of 30 patients (87%) received a reduced intensity conditioning regimen (RIC). The hematopoietic cell transplantation specific comorbidity index (HCT-CI) was two or less in 12/30 cases and three or more in 18/30 cases. All patients engrafted. One year Nonrelapse mortality (NRM) rate was 20% (6/30 cases). After a median follow-up of 16 months 17/30 patients (57%) were alive and in complete remission while 13/30 (43%) have died (leukemia refractory or relapse 7/13 and NRM 6/13). Median Overall Survival for the whole patient population was 28 months. The Overall Survival did not differ between unrelated and related donors. The patients transplanted in complete remission had a significantly lower survival rate and relapse rate compared to those transplanted with refractory or relapsed AML (P= 0.0004 and P= 0.008 respectively). The patients with a low HCT-CI (2 or less) had a significantly lower NRM (P = 0.03) and survival rate (P = 0.02) compared to those with HCT-CI 3 or more. Taking into account that this is a retrospective analysis with a small number of cases, these results confirm the feasibility of allo-SCT for high risk AML patients older than 60 years. Outcome was significantly influenced by status of disease at transplant and by HCT-CI. We also confirm that for older patients lacking a family donor MUD can provide a suitable alternative option

JAK-2 inhibitors and allogeneic transplant in myelofibrosis

7The activation of the JAK1/JAK2 pathway plays a crucial role in the pathogenesis of myelofibrosis. Treatment with the JAK2 inhibitor ruxolitinib demonstrated to reduce splenomegaly and symptoms in patients affected by myelofibrosis, leading to a significant improvement of overall survival in comparison with the supportive therapies. Taking in account this recent therapeutic progress, it is necessary to redefine the role of the allogeneic hematopoietic stem cell transplantation, which has been considered the only curative option for fit myelofibrosis patients up to now. In the era of JAK2 inhibitors, allogeneic transplant is still indicated in patients with intermediate-2 and high-risk myelofibrosis or red blood cell transfusion dependent patients or patients with unfavourable karyotype. There is no direct evidence to recommend which conditioning regimen should be preferentially adopted. Graft failure, relapse and transplant related mortality are still current issues of the allogeneic stem cell transplantation, particularly from unrelated donors. Ruxolitinib can be efficaciously included in the platform of allogeneic transplant. In fact, ruxolitinib treatment for 3-4 months before transplant has demonstrated to reduce spleen and improve performance status in about 30-50% of patients, without impairing the outcome of the subsequent transplant. Ruxolitinib has to stopped the day before conditioning to avoid rebound phenomenon. There are no sufficient data to recommend ruxolitinib administration after transplant with the aim of eradicating minimal residual disease and preventing relapse.openopenPatriarca, F; Sperotto, A; De Marchi, R; Perali, G; Cigana, C; Lazzarotto, D; Fanin, RPatriarca, Francesca; Sperotto, A; De Marchi, R; Perali, G; Cigana, C; Lazzarotto, D; Fanin, Renat

Experts’ consensus on the definition and management of high risk multiple myeloma

High risk multiple myeloma (HRMM) at diagnosis is currently recognized according to the Revised International Staging System (R-ISS) which was set up in 2015. Since then, new clinical and biological prognostic factors have been developed, which could implement the definition of High Risk (HR) category. We conducted a survey in order to identify which additional parameters, both clinical and biological, are considered more useful for the clinical practice and to evaluate if the management of Multiple Myeloma (MM) should change on the basis of the risk category. A questionnaire, consisting of 8 statements, was submitted to 6 Italian experts, from the European Myeloma Network (EMN) Research Italy, using the Delphi method. The colleagues were asked to answer each question using a scale between 0 and 100. If a statement did not reach at least 75 out of 100 points from all the participants, it was rephrased on the basis of the proposal of the experts and resubmitted in a second or further round, until a consensus was reached among all. From the first round of the survey a strong consensus was reached regarding the opportunity to revise the R-ISS including chromosome 1 abnormality, TP53 mutation or deletion, circulating plasma cells by next generation flow and extramedullary plasmacytomas. No consensus was reached for the definition of “double hit” MM and for the application in clinical practice of treatment strategies based on the risk category. In the second round of the Delphi questionnaire, “double-hit” MM was recognized by the association of at least two high-risk cytogenetic or molecular abnormalities. Moreover, the experts agreed to reserve an intensified treatment only to specific conditions, such as plasma cell leukaemia or patients with multiple extramedullary plasmacytomas, while they admitted that there are not sufficient real word data in order to modify treatment on the basis of MRD assessment in clinical practice. This survey suggests that the definition of HRMM should be implemented by additional clinical and biological risk factors, that will be useful to guide treatment in the future