Post-transplant events Combined administration of alpha-erythropoietin and filgrastim can improve the outcome and cost balance of autologous stem cell transplantation in patients with lymphoproliferative disorders

autologous transplantation; erythropoietin; engraftment kinetic

Multicenter Experience Using Total Lymphoid Irradiation and Antithymocyte Globulin as Conditioning for Allografting in Hematological Malignancies

A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day -11 through -1 with ATG at the dose of 1.5 mg/kg/day (from day -11 through -7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects

Choice of Frontline Tyrosine-Kinase Inhibitor and Early Events in Very Elderly Patients With Chronic Myeloid Leukemia in Chronic Phase: A "Campus CML" Study

Objectives: The study aimed to evaluate the utilization of frontline TKI therapy in a large cohort of elderly CP-CML patients. Methods: A retrospective analysis was conducted on 332 CP-CML patients aged 75 years or older among 1929 diagnosed from January 2012 to December 2019 followed at 36 participating Hematology Centers involved in the "Campus CML" project. Results: Among the patients analyzed, 85.8% received imatinib (IM) while 14.2% received second-generation TKIs (2G-TKI), 59.5% dasatinib, and 40.5% nilotinib. Most patients initiated IM at standard dose (67.3%) while 32.7% at reduced dose. A similar trend was observed with 2G-TKIs. The cumulative incidence of permanent TKI discontinuation at 12 months was 28.4%, primarily due to primary resistance (10.1%) and extra-hematologic toxicity (9.5%), with no significant difference between IM and 2G-TKI groups. Following the introduction of generic IM in Italy in 2018, IM usage increased significantly compared with 2G-TKIs. Conclusions: IM was in our Centers the preferred frontline therapy for older CP-CML patients, with increasing utilization after the introduction of generic formulations. However, 2G-TKIs are still used in a substantial proportion of patients, suggesting individualized physician assessments regarding patient suitability and expectations. Further investigation is needed to assess efficacy and safety of reduced TKI doses in this patient population

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

BackgroundImatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. MethodsA total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. ResultsSecond-generation TKIs were chosen for most patients aged <45 years (69.2%), whereas imatinib was used in 76.7% of patients aged >65 years (p < .001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with >3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age > 65 years, spleen size, the presence of comorbidities, and & GE;3 concomitant medications. ConclusionsThis observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use

Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate

Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate