Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD.

Background: The consequences of infectious toxicity of hypomethylating agents (HMAs) on overall survival (OS) of patients diagnosed with high-risk myeloid neoplasms have not been thoroughly investigated. Objectives: We aimed to evaluate whether infectious events (IEs) negatively influenced the results of HMA treatment in a real-world setting. Design: Observational study. Methods: We obtained data from 412 non-selected consecutive patients from 23 Spanish hospitals who were diagnosed with high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia and were treated with HMA. HMAs received after chemotherapy or stem cell transplant were excluded. All IEs were recorded. Outcomes included OS, modifications to the pre-planned treatment, incidence and characteristics of IEs, hospitalization, red blood cell transfusions, and factors associated with infection. Results: The rate of infection was 1.2 per patient/year. Next-cycle delay (p = 0.001) and hospitalizations (p = 0.001) were significantly influenced by IEs. Transfusion requirements during each cycle were significantly higher after infection compared with cycles without infection (coefficient = 1.55 [95% confidence interval (CI) = 1.26-1.84], p < 0.001). The median number of cycles was lower in patients experiencing any infection during the first four cycles (5 [3-8] versu 8 [5-16], p < 0.001). In the multivariable analysis, factors associated with lower OS were having any infection during the first four cycles (hazard ratio (HR) = 1.43 [95% CI = 1.09-1.88], p = 0.01), bone marrow blasts ⩾30% (HR = 2.13 [95% CI = 1.14-3.96], p = 0.01), adverse cytogenetics (HR = 1.70 [95% CI = 1.30-2.24], p < 0.001), and platelet count <50 × 109/l (HR = 1.69 [95% CI = 1.3-2.2], p < 0.001). BM blasts >20% (HR = 1.57 [95% CI = 1.19-2.01], p < 0.001) and adverse cytogenetics (HR = 1.7 [95% CI = 1.35-2.14], p < 0.001) were associated with infection, whereas hemoglobin >9 g/dl (HR = 0.65 [95% CI = 0.51-0.82], p < 0.001) and higher platelet count (HR = 0.997 [95% CI = 0.996-0.998], p = 0.016) protected from it. Conclusion: HMA infectious toxicity worsens OS, hinders the adherence to antineoplastic treatment and results in significant morbidity. Preventive strategies are fundamental in vulnerable patients.

Estudio prospectivo del seguimiento de pacientes largos supervivientes a un trasplante alogénico de progenitores hematopoyéticos / Prospective follow-up of adult long-term survivors of allogeneic haematopoietic stem cell transplantation

Fundamento y objetivo: Los pacientes que sobreviven más allá de 2 años del trasplante de progenitores hematopoyéticos (TPH), tienen un riesgo aumentado de complicaciones a largo plazo, que tienen impacto en su supervivencia y calidad de vida. El objetivo de este estudio fue diseñar y aplicar un protocolo de seguimiento a largo plazo para detectar necesidades no cubiertas y tratar precozmente dichas complicaciones.Pacientes y métodoA los supervivientes más allá de 2 años del TPH alogénico (aloTPH) se aplicó una sistemática de estudio para detectar y tratar complicaciones y problemas a largo plazo dentro de una unidad funcional interdisciplinar.ResultadosTreinta y seis (36%) de los 99 pacientes incluidos, requirieron de intervención en alguno de los factores de riesgo cardiovascular mediante educación sanitaria o administración de fármacos antihipertensivos e hipolipemiantes. Nueve (25%) de 36 pacientes requirieron aporte de calcio y vitamina D. Se detectó una baja reincorporación de las mujeres a los protocolos de detección de neoplasias ginecológicas, y una baja adherencia al seguimiento odontológico tras el aloTPH.ConclusiónEl seguimiento de los largos supervivientes a un aloTPH en una unidad multidisciplinaria permitió detectar necesidades no cubiertas, que afectaron especialmente al riego cardiovascular, metabolismo óseo, prevención del cáncer y control odontológico. (AU)

Background and objective: Patients who survive beyond two years after haematopoietic stem cell transplantation (HSCT) have an increased risk of long-term complications, which impact on their survival and quality of life. The aim of this study was to design and apply a long-term follow-up protocol to detect unmet needs and treat these complications early.Patients and methodA prospective study to detect and treat complications and long-term problems within an interdisciplinary functional unit was applied to survivors beyond 2 years of allogeneic HSCT (alloHSCT).ResultsThirty-six (36%) of the 99 patients included, required intervention in a cardiovascular risk factor by health education or antihypertensive and lipid-lowering drugs. Nine of 36 (25%) patients required calcium and vitamin D intake. Low inclusion of women in gynaecological neoplasm detection protocols was detected, as well as a low adherence to dental follow-up after alloHSCT.ConclusionThe follow-up of long-term survivors after alloHSCT in a multidisciplinary unit allowed unmet needs to be detected and controlled, especially in cardiovascular risk, bone metabolism, cancer prevention, and dental control. (AU)

Outcomes of patients with chronic myelomonocytic leukaemia treated with non-curative therapies: a retrospective cohort study.

BACKGROUND: Approval of hypomethylating agents in patients with chronic myelomonocytic leukaemia is based on trials done in patients with myelodysplastic syndromes. We aimed to investigate whether hypomethylating agents provide a benefit in subgroups of patients with chronic myelomonocytic leukaemia compared with other treatments. METHODS: For this retrospective cohort study, data were retrieved between Nov 30, 2017, and Jan 5, 2019, from 38 centres in the USA and Europe. We included non-selected, consecutive patients diagnosed with chronic myelomonocytic leukaemia, who received chronic myelomonocytic leukaemia-directed therapy. Patients with acute myeloid leukaemia according to 2016 WHO criteria at initial diagnosis (ie, ≥20% blasts in the bone marrow or peripheral blood) or with unavailability of treatment data were excluded. Outcomes assessed included overall survival, time to next treatment, and time to transformation to acute myeloid leukaemia. Analyses were adjusted by age, sex, platelet count, and Chronic myelomonocytic leukaemia-Specific Prognostic Scoring System (CPSS). Patients were grouped by first received treatment with either hydroxyurea, hypomethylating agents, or intensive chemotherapy, and stratified by risk according to blast count, French-American-British subtype, CPSS, WHO 2016 subtype, and the eligibility criteria of the DACOTA trial (NCT02214407). FINDINGS: 949 patients diagnosed with chronic myelomonocytic leukaemia between April 13, 1981, and Oct 26, 2018, were included. Median follow-up was 23·4 months (IQR 11·5-42·3) from diagnosis and 16·2 months (6·6-31·6) from start of first-line treatment. 412 (43%) of 949 patients received hypomethylating agents as first treatment, 391 (41%) hydroxyurea, and 83 (9%) intensive chemotherapy. Adjusted median overall survival for patients treated with hydroxyurea versus hypomethylating agents was 15·6 months (95% CI 13·1-17·3) versus 20·7 months (17·9-23·4); hazard ratio (HR) 1·39 (1·17-1·65; p=0·0002) and 14·0 months (9·8-17·2) versus 20·7 months (17·9-23·4; HR 1·55 [1·16-2·05]; p=0·0027) for those treated with intensive chemotherapy versus hypomethylating agents. In patients with myeloproliferative chronic myelomonocytic leukaemia (myeloproliferative CMML), median overall survival was 12·6 months (10·7-15·0) versus 17·6 months (14·8-21·5; HR 1·38 [1·12-1·70]; p=0·0027) for patients treated with hydroxyurea versus hypomethylating agents, and 12·3 months (8·4-16·6) versus 17·6 months (14·8-21·5; HR 1·44 [1·02-2·03]; p=0·040) for intensive chemotherapy versus hypomethylating agents. Hypomethylating agents did not confer an overall survival advantage for patients classified as having lower-risk disease (ie, myelodysplastic chronic myelomonocytic leukaemia with <10% blasts, CMML-0, or lower-risk CPSS). INTERPRETATION: These data suggest hypomethylating agents as the preferred therapy for patients with higher-risk chronic myelomonocytic leukaemia and those with myeloproliferative CMML. Our findings also suggest that CPSS is a valuable tool to identify patients who are most likely to benefit from hypomethylating agents. Further evidence from prospective cohorts would be desirable. FUNDING: The Austrian Group for Medical Tumor Therapy.

Post-transplant cyclophosphamide for GVHD prophylaxis compared to ATG-based prophylaxis in unrelated donor transplantation.

Post-transplant cyclophosphamide (PTCY) effectively prevents graft-versus-host disease after unmanipulated HLA-haploidentical HSCT. The use of PTCY in the unrelated donor HSCT setting is less explored. We conducted a retrospective study of 132 consecutive patients undergoing a matched or 9/10 mismatched unrelated donor HSCT in 4 centers in Spain, 60 with anti-thymocyte globulin (ATG)-based prophylaxis combined with MTX-CsA, and 72 using a PTCY-based regimen. Peripheral blood stem cells were used as graft in most patients (111 patients, 84%); mMUD donors were balanced between groups. Cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days were lower in the PTCy group (46% vs. 67%, p = 0.008; 3% vs. 34%, p = 0.003), without statistically significant differences in the 2-year cumulative incidence of chronic moderate-severe GVHD. At 2 years, no significant differences were observed in overall survival, event-free survival, cumulative incidence of relapse, and non-relapse mortality. GVHD was the most frequent cause of NRM in the ATG group. No differences were observed between groups in the composite endpoint of GVHD-free and relapse-free survival. In this study, PTCy combined with additional immunosuppression after MUD/mMUD HSCT showed a reduction of aGVHD rate with safety results comparable to those obtained with the ATG-based prophylaxis.

Prospective follow-up of adult long-term survivors of allogeneic haematopoietic stem cell transplantation. / Estudio prospectivo del seguimiento de pacientes largos supervivientes a un trasplante alogénico de progenitores hematopoyéticos.

BACKGROUND AND OBJECTIVE: Patients who survive beyond two years after haematopoietic stem cell transplantation (HSCT) have an increased risk of long-term complications, which impact on their survival and quality of life. The aim of this study was to design and apply a long-term follow-up protocol to detect unmet needs and treat these complications early. PATIENTS AND METHOD: A prospective study to detect and treat complications and long-term problems within an interdisciplinary functional unit was applied to survivors beyond 2 years of allogeneic HSCT (alloHSCT). RESULTS: Thirty-six (36%) of the 99 patients included, required intervention in a cardiovascular risk factor by health education or antihypertensive and lipid-lowering drugs. Nine of 36 (25%) patients required calcium and vitamin D intake. Low inclusion of women in gynaecological neoplasm detection protocols was detected, as well as a low adherence to dental follow-up after alloHSCT. CONCLUSION: The follow-up of long-term survivors after alloHSCT in a multidisciplinary unit allowed unmet needs to be detected and controlled, especially in cardiovascular risk, bone metabolism, cancer prevention, and dental control.

Lack of impact of human immunodeficiency virus infection on the outcome of lymphoma patients transferred to the intensive care unit.

The impact of human immunodeficiency virus (HIV) infection on the outcome of patients with acquired immunodeficiency syndrome (AIDS)-related lymphoma with life-threatening complications requiring intensive care unit (ICU) admission is not well known. The objective of this study was to compare the outcome of patients with lymphoma transferred to the ICU according to HIV infection status. The clinical characteristics, reason for ICU admission, and outcome of 48 consecutive critically ill patients with lymphoma admitted to the ICU from January 2000 to March 2010 was retrospectively analyzed, focusing on their HIV serology status. Thirty-six patients were HIV-negative and 12 patients HIV-positive. Burkitt lymphoma was more frequent in HIV-infected patients, whereas diffuse large B-cell lymphoma was more frequent in HIV-negative patients. The main acute life-threatening diseases precipitating ICU transfer were similar in both groups. Severe neutropenia was more frequent in HIV-positive than in HIV-negative patients. With a median follow-up of 53 months after ICU admission, the overall survival probabilities were 15% (95% confidence interval [CI]: 3-27%) and 17% (95% CI: 0-38%) for HIV-negative and HIV-positive patients, respectively. The 2-year survival probabilities were 34% (95% CI: 10-58%) and 40% (95% CI: 0-43%) for HIV-negative and HIV-positive patients discharged from the ICU, respectively. In this study, HIV infection did not have a negative impact on the outcome of patients with lymphoma admitted to the ICU.

Análisis de la implantación de la acreditación del Joint Acreditation Committee of the International Society for Cellular Therapy and European Group for Blood and Marrow Transplantation en un programa clínico de trasplante de progenitores hematopoyéticos / Analysis of the implementation of a Joint Acreditation Committee of the International Society for Cellular Therapy and European Group for Blood and Marrow Transplantation acreditation in a clinical program of hematopoietic progenitor cell transplantation

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