Prolonged response to recombinant human erythropoietin treatment in patients with myelodysplastic syndrome at a single referral centre in Brazil

OBJECTIVES: To evaluate the effects of epoetin (EPO) alfa treatment on overall survival, event-free survival and response duration in patients with myelodysplastic syndrome (MDS) who were treated at a haematological referral centre in northeastern Brazil. METHODS: This was a retrospective cohort study of 36 patients diagnosed with MDS and treated with EPO alfa at 30,000 to 60,000 IU per week. Clinical data were collected from medical records. The events assessed were non-response to treatment and progression to acute myeloid leukaemia (AML). Statistical analyses were performed using GraphPad Prism 7 and SPSS 24 software. RESULTS: The overall survival of patients who received EPO alfa treatment was 51.64%, with a median of 65 months of treatment, and the overall survival of this group was 100% during the first 24 months. We detected a 43.5-month median event-free survival, with a response rate of 80.5%. We observed responses from 25 to 175 months. Patients with transfusion dependence and those with a high-risk stratification, as determined by the International Prognostic Scoring System (IPSS), the Revised International Prognostic Scoring System (IPSS-R), the WHO classification-based Prognostic Scoring System (WPSS) and the WHO 2016, had a lower event-free survival than other patients. CONCLUSIONS: Despite the wide use of EPO alfa in the treatment of anaemia in patients with MDS, the median response duration is approximately only 24 months. Our data provide encouraging results concerning the benefits of using EPO alfa for the improvement of the quality of life, as patients treated with EPO showed higher overall survival, event-free survival rates and longer response durations than have been previously described in the literature.

Salvaged single-unit cord blood transplantation for 26 patients with hematologic malignancies not in remission

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02)×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65)×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days) and had platelet counts of >20×109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Myelodysplastic syndromes (MDS): prognostic factors and scoring systems

To evaluate the score systems of Cassano and Sanz and suggest a new one. Design: Case series. Location: Teaching hospitals: EPM UNIFESP and Faculdade de Medicina de Botucatu. Participants: 59 patients diagnosed from 1979 to 1992. Intervention: Evaluation of clinical-laboratorial data. Measurement: Statistical comparison, uni and multivariate analysis and actuarial survival curves. Results: Cassano's system divided the patients into high and low risk (p=0.0966) while Sanz's gave high, intermediate and low risk (p=0.0108). The univariate analysis showed hemoglobin, WBC count, E/M ratio, liver size and blast percentage in BM as statistically significant. The multivariate analysis showed blast percentage in BM (p=0.004) and Hb (p=0.050) as signigicant. Our system, considering the multivariate analysis data, divided the patients into high, intermediate and low risk (p=0.0038). Conclusions: Sanz's system was more functional than Cassano's, while ours showed predictive survival value and ease of use in clinical practice.

Myelodysplastic syndrome. A clinical and pathological analysis of 88 patients.

Eighty eight patients with myelodysplastic syndromes were studied to determine the clinical and pathological features and the prognosis. All the patients had anemia. Neutropenia was seen in 44% and thrombocytopenia in 78% patients. The subtypes included refractory anemia in six, refractory anemia with ringed sideroblasts in three, refractory anemia with excess blasts in 30, refractory anemia with excess blasts in transformation in 32 and chronic myelomonocytic anemia in 17 patients. Forty four patients who received chemotherapy were evaluable for response. Three of the 15 patients treated with hydroxyurea achieved partial remission. Eighteen patients were treated with low dose cytosine arabinoside and complete remission was achieved in five and partial response in six patients. Aggressive chemotherapy was given to 11 patients at the onset of the illness resulting in complete remission in six and partial response in two patients. Nineteen of the 88 patients transformed to acute myeloid leukemia. The crude survival of all the patients ranged from 15 days to 22.5 months. The mortality was due to hemorrhage in 15% and septicemia in 85%. Our data reveals ineffectiveness of the current therapy and emphasizes on the need to develop newer therapeutic approaches.

Sindromes mielodisplasticos: experiencia del grupo de estudio y tratamiento de las insuficiencias medulares (Getim) / Myelodysplastic syndromes: experience of the study groups and treatment of medullary failure (Getim)

Se estudiaron 58 pacientes con síndromes mielodisplásticos (SMD), clasificados según los criterios de la FAB. La edad promedio del grupo fue de 61 años (entre 18 y 81). Se evaluaron las alteraciones morfológicas en sangre y médula ósea y los depósitos de hierro extra e intracelulares. Se realizó también determinación de peroxidasa, fosfatasa alcalina lucocitaria, estudio histopatológico de médula ósea, estudio citogenético y cultivo de precursores granulocito-macrofágicos (CFU-GM) en cierto número de pacientes. Hubo seguimiento clínico en 49 pacientes, siendo la sobrevida media observada en los pacientes con anemia rafractaria (AR) de 36,7 meses y los portadores de anemia refractaria con exceso de blastos (AREB) de 15,5 meses. No se obtuvo dato de sobrevida en los otros grupos: anemia sideroblástica (AS), AREB em transformación (AREB-T) y leucemia mielomonocítica crónica (LMMC) por contar pocos pacientes en cada uno. En el momento del diagnóstico, 28 pacientes estaban asintomáticos. Durante la evolución las principales manifestaciones fueron anemia con necesidad tansfusional, infecciones bacterianas y hemorragias cutáneo-mucosas predominantemente. Ocho pacientes fallecieron por leucemia aguda, seis por complicaciones de la citopenia, uno por insuficiencia hepática y cuatro por causas intercurrentes. Fue inconstante el beneficio obtenido con los distintos tratamientos aplicados en forma no randomizada. Consistieron en administración de oximetolona, prednisolona, vitaminas B1, B6. B12, C y folatos; citosina arabinósido a dosis bajas; y ácido 13 cis retinoico. Diez pacientes sufrieron la tansformación a leucemia aguda. No se observó ninguna remisión completa en los seis paciente que recibieron algún tipo de tratamiento antileucémico