Characteristics and outcome of patients with core-binding factor acute myeloid leukemia and FLT3-ITD: results from an international collaborative study.

The aim of this study was to evaluate the prognostic impact of FLT3-ITD in core-binding factor acute myeloid leukemia (CBFAML) in an international, multicenter survey of 97 patients of whom 52% had t(8;21)(q22;q22) and 48% had inv(16)(p13q22)/t(16;16)(p13;q22). The median age of the patients was 53 years (range, 19-81). Complete remission after anthracycline-based induction (n=86) and non-intensive therapy (n=11) was achieved in 97% and 36% of the patients, respectively. The median follow-up was 4.43 years (95% confidence interval [95% CI]: 3.35-7.39 years). The median survival after intensive and non-intensive treatment was not reached and 0.96 years, respectively. Among intensively treated patients, inv(16) with trisomy 22 (n=11) was associated with a favorable 4-year relapse-free survival rate of 80% (95% CI: 59-100%) as compared to 38% (95% CI: 27-54%; P=0.02) in all other patients with CBFAML/ FLT3-ITD (n=75). Overall, 24 patients underwent allogeneic hematopoietic cell transplantation (HCT), 12 in first complete remission and 12 after relapse. Allogeneic HCT in first complete remission was not beneficial (P=0.60); however, allogeneic HCT seemed to improve median survival in relapsed patients compared to that of patients treated with chemotherapy (not reached vs. 0.6 years, respectively; P=0.002). Excluding patients with inv(16) with trisomy 22, our data indicate that compathe outcome of CBF-AML patients with FLT3-ITD may be inferior to that of patients without FLT3-ITD (based on previously published data), suggesting that prognostically CBF-AML patients with FLT3-ITD should not be classified as favorable-risk. FLT3-inhibitors may improve the outcome of these patients.

Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study.

In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3-CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16-75) years. AML was de novo in 58%, therapy-related (t-AML) in 37% and secondary after myelodysplastic syndrome (s-AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3-CREBBP, whole-genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9-1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow-up was 5·48 years; five-year survival rate was 17%. Patients with s-/t-AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo-HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo-HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo-HCT in CR1 was effective in de novo AML but not in patients with s-AML/t-AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo-HCT performed in CR1.

Dasatinib treatment long-term results among imatinib-resistant/intolerant patients with chronic phase chronic myeloid leukemia are favorable in daily clinical practice.

To evaluate long-term real-life results of dasatinib therapy among chronic phase chronic myeloid leukemia patients resistant or intolerant to imatinib, we retrospectively analyzed data of 118 patients treated in centers participating in the database INFINITY. With median follow-up of 37 months, estimated 5-year cumulative incidences of complete cytogenetic and major molecular responses were 78% and 68%, respectively. The estimated 5-year probability of overall survival (OS) and event-free survival (EFS) were 86% and 83%, respectively. Both OS and EFS were significantly improved among patients with BCR-ABL1 transcript level ≤10% at 3 months. Dasatinib toxicity was tolerable however persistent in almost half our patients, even after years of therapy. Pleural effusion occurred in 29% of patients and was responsible for 30% of dasatinib discontinuations. Our results confirmed very good efficacy and acceptable toxicity of dasatinib in second line setting and support the evidence and importance of high-quality real-life CML patient management.

How to select older patients with acute myeloid leukemia fit for intensive treatment?

Outcomes of the treatment of older patients with acute myeloid leukemia (AML) are unsatisfactory due to a higher incidence of negative patient- and disease-related risk factors connected with aging. Prediction of poor tolerance to aggressive treatment and low response to standard intensive chemotherapy are the main root causes why the treatment decision is challenging. For a long time, negative prognostic factors for treatment outcomes, overall survival, and early death such as the age itself, low-performance status, high-comorbidity burden, adverse cytogenetics, and secondary AML have been known, and they are routinely taken into account during therapeutic balance. In consideration of the risk factors and specific laboratory results, prognostic models have been created. Despite the abovementioned facts, the survival of older patients with AML remains very poor, that holds true even for the intensive therapy. For that reason, there is an increased effort to find a better approach how to select patients who would benefit from intensive treatment without decreasing their quality of life through severe complications with risk of high treatment-related mortality. Based on the results of clinical studies, the geriatric assessment could be the missing step which would help select older patients who are really fit for intensive treatment and who will benefit from it the most. This review focuses on the risk factors that should be taken under advisement when the decision about the treatment is made. With reference to the published information, we propose an algorithm how to identify fit, vulnerable, and frail patients.

Extravasation (paravasation) of chemotherapy drugs - updated recommendations (2020) for standard care in the Czech Republic from the cooperation of the Supportive Care Group of the Czech Society for Oncology, Czech Society for Hematology, Oncology Section of the Czech Nurses Association and the Society for Ports and Permanent Catheters.

BACKGROUNDS: Extravasation (paravasation) of chemotherapy drugs is a very significant complication. Preventive and therapeutic interventions reduce the risk of the complication or the extent of its consequences. A working group of authors from expert groups prepared recommendations for standard care. PURPOSE: A basic summary of recommended interventions for daily practice, defined on the basis of knowledge from long-term, proven, evidence-based practice or on the consensus opinions of the expert groups representatives. RESULTS: Preventive measures are essential and include early consideration of long-term venous access devices indications, choice of injection site, venous line control before each chemotherapy drug application, and patient education. The intervention in case of extravasation mainly involves the application of antidotes (DMSO, hyaluronidase, dexrazoxane) and the application of dry cold or heat according to the type of cytostatic drug. Subcutaneous corticosteroids, moist heat or cooling and compression are not recommended. CONCLUSION: The recommended procedures contribute to reducing the risk and consequences of extravasation. The range of recommended interventions can be expanded individually depending on individual clinical site policy and needs.