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In patients with lower-risk myelodysplastic syndromes/neoplasms (MDS), response to first-line therapy is limited and transient. The MATTERHORN randomized, double-blind, phase 3 trial evaluated roxadustat versus placebo for patients with transfusion-dependent, lower-risk MDS. Eligible patients had very low-, low-, or intermediate-risk MDS with or without prior erythropoiesis-stimulating agent treatment, and a transfusion burden of 1-4 packed red blood cell (pRBC) units every 8 weeks (Q8W). Patients were randomized (3:2) to oral roxadustat (2.5 mg/kg) or placebo, both three times weekly, with best supportive care. Primary efficacy endpoint was transfusion independence (TI) for ≥56 days within 28 weeks (TI responders). MATTERHORN was terminated due to interim analysis outcomes not meeting statistical significance. In total, 272 patients were screened, and 140 patients were enrolled (82, roxadustat, and 58, placebo). At final analysis, 38/80 (47.5%) patients and 19/57 (33.3%) in the roxadustat and placebo arms, respectively, were TI responders (p = .217). A greater percentage of patients in the roxadustat arm with a transfusion burden of ≥2 pRBC units Q4W were TI responders (36.1%; 13/36) compared with the placebo arm (11.5%; 3/26; p-nominal = .047). The seven on-study deaths (4, roxadustat, and 3, placebo) were considered unrelated to treatment. Three roxadustat patients progressed to acute myeloid leukemia. Despite MATTERHORN not meeting its primary endpoint, a numerically higher TI rate was achieved with roxadustat treatment compared with placebo. Further analyses are needed to confirm the MDS patient subgroups deriving clinical benefit from this novel treatment.
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Glicina , Isoquinolinas , Síndromes Mielodisplásicas , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Masculino , Método Duplo-Cego , Feminino , Isoquinolinas/uso terapêutico , Isoquinolinas/administração & dosagem , Pessoa de Meia-Idade , Glicina/análogos & derivados , Glicina/uso terapêutico , Glicina/administração & dosagem , Idoso de 80 Anos ou mais , Resultado do Tratamento , Adulto , Transfusão de EritrócitosRESUMO
Information on causes of death (CoDs) and the impact of myelodysplastic syndromes (MDS) on survival in patients with lower-risk MDS (LR-MDS) is limited. A better understanding of the relationship between disease characteristics, clinical interventions and CoDs may improve outcomes of patients with LR-MDS. We prospectively collected data on patients with LR-MDS in the European MDS registry from 2008 to 2019. Clinical, laboratory and CoDs data were obtained. To examine MDS-specific survival, relative survival (RS) was estimated using national life tables. Of 2396 evaluated subjects, 900 died (median overall survival [OS]: 4.7 years; median follow-up: 3.5 years). The most common CoDs were acute myeloid leukaemia/MDS (20.1%), infection (17.8%) and cardiovascular disease (CVD; 9.8%). Patients with isolated del(5q) and with red cell transfusion needed during the disease course, had a higher risk of fatal CVD. The 5-year OS was 47.3% and the 5-year RS was 59.6%, indicating that most patients died due to their underlying MDS. Older patients (aged >80 years) and the lowest-risk patients were more likely to die from competing causes. This study shows that MDS and its related complications play crucial role in the outcome of patients with LR-MDS.
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Doenças Cardiovasculares , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Causas de Morte , Progressão da Doença , Sistema de RegistrosRESUMO
INTRODUCTION: Venetoclax combined with azacitidine (AZA-VEN) constitutes an option for the treatment of acute myeloid leukemia. There are, however, no data on the COVID-19 incidence and outcome in patients treated with AZA-VEN. METHODS: Patients with acute leukemia treated with AZA-VEN at a single institution were included in this prospective observational study. RESULTS: Thirteen patients were enrolled, 46% with treatment-naïve, and 56% with relapsed/refractory disease. Fifty-four percent of patients were males; the median age was 69 years. Six patients (46%) developed COVID-19 during the observation time. The median time to COVID-19 was 24 days from the initiation of AZA-VEN. The 2-month cumulative incidence of COVID-19 was 46.2%. Two patients (33%) succumbed to COVID-19. The 100-day COVID-19-free survival from AZA-VEN initiation was 61%. The median follow-up time was 4.3 months. DISCUSSION/CONCLUSION: COVID-19 constitutes a frequent complication of AZA-VEN treatment in the era of the COVID-19 pandemic, leading to death in a significant proportion of patients.
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COVID-19 , Leucemia Mieloide Aguda , Masculino , Humanos , Idoso , Feminino , Azacitidina/efeitos adversos , Pandemias , SARS-CoV-2 , Leucemia Mieloide Aguda/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
A combination of azacitidine and venetoclax (AZA-VEN) has been approved for the treatment of adult treatment-naïve acute myeloid leukemia (AML) patients, ineligible for intensive chemotherapy. The protocol may also constitute an alternative for the treatment of patients with mixed phenotype acute leukemia (MPAL), for which no established treatment guidelines exist. It may be anticipated, that alike in AML or chronic lymphocytic leukemia, the treatment of MPAL may be complicated by the tumor lysis syndrome (TLS). No case of TLS in MPAL after VEN has been however reported so far. Here, we present a case of a patient with MPAL, who received AZA-VEN. The patient had a substantial bulk of disease with generalized lymphadenopathy and increased white blood cell count. Despite preventive measures, the patient developed the clinical TLS, which was successfully treated. Based on the current case and other published cases, the incidence of TLS after AZA-VEN was established at 17%.
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Leucemia Mieloide Aguda , Síndrome de Lise Tumoral , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Fenótipo , Sulfonamidas , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/tratamento farmacológico , Síndrome de Lise Tumoral/etiologiaRESUMO
Secondary immunodeficiencies are frequently observed after allo-HSCT. The efficacy of subcutaneous IgG preparations in this population is unknown. A retrospective single-institution study involved 126 adult patients transplanted in 2012-2019 for hematological malignancies. Patients were tested every 2-3 weeks for plasma IgG concentration during the 1st year after transplantation and supplemented with facilitated subcutaneous immunoglobulin when they either had IgG concentration < 500 mg/dl or between 500 and 700 mg/dl and recurrent infection. The IgG concentration < 500 mg/dL was diagnosed in 41 patients, while 500-700 mg/dL in 25 and altogether 53 patients received IgG supplementation. The median number of IgG administrations was 2. The median time to the first IgG administration after allo-HSCT was 4.1 months, while to the next administration (if more than one was required) 53 days (prophylactic group) and 32 days (group with infections). We did not observe any significant toxicity. Two situations were associated with increased probability of meeting criteria for IgG supplementation: diagnosis of either acute lymphoblastic leukemia (ALL) or chronic lymphocytic leukemia (CLL) (83.8% versus 39.3% for other diagnosis, p = 0.000) and the systemic use of corticosteroids (64.2% versus 31.5% for patients without systemic corticosteroids, p = 0.005). Over 40% of the adult recipients may require at least incidental immunoglobulin supplementation during the first year after allo-HSCT. Low IgG concentrations are associated with inferior outcomes. The subcutaneous route of IgG administration appeared to be safe and may allow for long persistence.
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Agamaglobulinemia/etiologia , Agamaglobulinemia/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunoglobulinas/uso terapêutico , Administração Cutânea , Adulto , Agamaglobulinemia/sangue , Gerenciamento Clínico , Feminino , Neoplasias Hematológicas/terapia , Humanos , Imunoglobulinas/administração & dosagem , Imunoglobulinas/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Adulto JovemRESUMO
OBJECTIVES: Relapse of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) belongs to the major causes of treatment failure. METHODS: Retrospective multicenter analysis of patients diagnosed with AML or MDS who had hematological relapse after allo-HSCT and were treated with azacitidine for this indication. RESULTS: Twenty-three patients receiving azacitidine as the first treatment of relapse (Group_1) and 8 patients receiving azacitidine after other treatment of relapse (Group_2) were included. There were 68% males, median age at initiation of azacitidine was 53 years (15-66). Median time to relapse was 3.5 months and 6.3 months in Group_1 and Group_2, respectively; median time from relapse to azacitidine 0.2 and 2.3 months. Azacitidine 75 mg/m2 , days 1-7, was administered in 78% and 75% of patients in Group_1 and Group_2, concomitant DLI in 48% and 50%. With median follow-up of 4.7 and 13.6 months, the median overall survival was 5.9 and 9.5 months. 17% and 37.5% patients proceeded to salvage allo-HSCT, with median OS of 11.6 months and not reached respectively. CONCLUSIONS: Azacitidine treatment for hematological relapse is associated with poor outcome; nevertheless, a proportion of patients may benefit from it, including patients receiving subsequent salvage allo-HSCT.
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Azacitidina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Salvage autologous hematopoietic stem cell transplantation (autoHSCT) may be used to treat relapse of multiple myeloma occurring after previous autoHSCT. When insufficient number of hematopoietic stem cells was stored from the initial harvest, remobilization of stem cells is necessary. PURPOSE: The analysis of stem cell remobilization after previous autoHSCT. PATIENTS AND METHODS: Fifty-eight patients, 60% males, median 59 years, were included. Median time interval between autoHSCT and remobilization was 42 months. The first remobilization was performed mostly after chemotherapy: cyclophosphamide (33%), cytarabine (43%), and etoposide (19%). RESULTS: The first remobilization was successful in 67% patients. About 19% patients required plerixafor rescue, among whom it allowed for successful harvesting in 14%. Use of cyclophosphamide, cytarabine, and etoposide allowed for successful remobilization in 53%, 84%, and 55% patients, respectively. Patients treated with cytarabine had the highest yield of CD34+ cells (median 7.5 × 106 /kg vs 5.8 and 2.4 for etoposide and cyclophosphamide, P = .001). Higher percentage of patients was able to collect ≥2 × 106 CD34+ cells/kg during one leukapheresis after cytarabine (76% vs 21% for cyclophosphamide vs 36% for etoposide, P = .001). Cytarabine use was associated with lower risk of remobilization failure OR = 0.217, P = .02. Toxicity comprised mostly hematological toxicity (thrombocytopenia and neutropenia). One patient succumbed to septic shock. CONCLUSION: Remobilization after previous autoHSCT is feasible only in a proportion of patients. Cytarabine is associated with the highest rate of successful mobilization and the highest yield of mobilized CD34+ cells. The toxicity requires careful surveillance of these patients.
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Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Transplante AutólogoRESUMO
Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after iron chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860.
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Sobrecarga de Ferro , Síndromes Mielodisplásicas , Terapia por Quelação , Humanos , Ferro/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Síndromes Mielodisplásicas/tratamento farmacológico , Sistema de Registros , Estudos RetrospectivosRESUMO
Progression-free survival (PFS) of patients with lower-risk myelodysplastic syndromes (MDS) treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals from newly diagnosed lower-risk myelodysplastic syndromes patients in 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk MDS/acute myeloid leukemia as events. Of the 1,267 patients included in the analyses, 317 died without progression; in 162 patients the disease had progressed. PFS was significantly associated with age, EQ-5D index, baseline World Health Organization classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with PFS (P<1×10-4): dose density had an increasing effect on hazard until a dose density of 3 units/16 weeks. The transfusion dose density effect continued to increase beyond 8 units/16 weeks after correction for the impact of treatment with erythropoiesis-stimulating agents, lenalidomide and/or iron chelators. In conclusion, the negative effect of transfusion treatment on PFS already occurs at transfusion densities below 3 units/16 weeks. This indicates that transfusion dependency, even at relatively low dose densities, may be considered as an indicator of inferior PFS. This trial was registered at www.clinicaltrials.gov as #NCT00600860.
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Síndromes Mielodisplásicas , Transfusão de Eritrócitos/efeitos adversos , Europa (Continente) , Humanos , Israel/epidemiologia , Síndromes Mielodisplásicas/terapia , Intervalo Livre de Progressão , Estudos ProspectivosRESUMO
Atypical chronic myeloid leukaemia (aCML) belongs to myelodysplastic/myeloproliferative neoplasms. Because of its rarity and changing diagnostic criteria throughout subsequent classifications, data on aCML are very scarce. Therefore, we at the Polish Adult Leukemia Group performed a nationwide survey on aCML. Eleven biggest Polish centres participated in the study. Altogether, 45 patients were reported, among whom only 18 patients (40%) fulfilled diagnostic criteria. Among misdiagnosed patients, myelodysplastic/myeloproliferative syndrome unclassifiable and chronic myelomonocytic leukaemia were the most frequent diagnoses. Thirteen patients were male, median age 64.6 years (range 40.4-80.9). The median parameters at diagnosis were as follows: white blood cell count 97 × 109 /L (23.8-342) with immature progenitors amounting at 27.5% (12-72), haemoglobin 8.6 g/dL (3.9-14.9), and platelet count 66 × 109 /L (34-833). Cytoreductive treatment was used in all patients, and 2 patients underwent allogeneic hematopoietic stem cell transplantation. The median overall survival was 14.1 months (95% CI, 7.2), with median acute myeloid leukaemia-free survival of 13.3 months (95% CI, 3.6-22.6). Cumulative incidence of acute myeloid leukaemia transformation after 1 year in aCML group was 12.5% (95% CI, 0%-29.6%). To conclude, aCML harbours a poor prognosis. Treatment options are limited, with allogeneic hematopoietic stem cell transplantation being the only curative method at present, although only a minority of patients are transplant eligible. Educational measures are needed to improve the quality of diagnoses.
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INTRODUCTION: Dialysis-dependent (DD) multiple myeloma patients (MM) have a poor prognosis and high tumour burden, thus may benefit from autologous peripheral blood stem cell transplantation (auto-PBSCT), however, these patients have an increased risk of toxicity. AIMS: To evaluate the outcomes (toxicity, PFS, OS) of high dose therapy followed by auto-PBSCT during an observational study and after propensity score matching. PATIENTS AND METHODS: Between 2004-2015, 24 DD patients, (aged 38-67 years), ISS 3, treated with auto-PBSCT, requiring dialysis at diagnosis and auto-PBSCT were evaluated, matched and compared to 55 normal renal function MM patients (NRF) with ISS 3 for outcomes of interest. RESULTS: In DD patients compared to NRF patients risk of mucositis (88% vs 55%), infection (79% vs 51%), parenteral nutrition (50% vs 24%), diarrhoea (71% vs 38%), prolonged duration of hospitalisation (medians: 30 vs 21 days), requirement for RBC transfusion (83% vs 36%) were significantly higher, while no significant differences were found in post-transplant response (ORR; 75% vs 87%), 5-year PFS (36% vs 20%) and OS (39% vs 50%). Subgroup analyses based on toxicity supported these results. CONCLUSIONS: Despite the increased risk of toxicity in DD patients these events do not significantly affect both the PFS and OS.
Assuntos
Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico , Diálise Renal , Adulto , Idoso , Biomarcadores , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Polônia , Insuficiência Renal/complicações , Insuficiência Renal/terapia , Transplante AutólogoRESUMO
INTRODUCTION: High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto-HSCT is also a feasible therapeutic option in MM dialysis-dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected. MATERIALS AND METHODS: Given that data on mobilization of auto-HSC efficacy and safety in dialysis-dependent patients are limited, we report data from all Polish Centers belonging to the Polish Myeloma Study Group. Twenty-eight dialysis-dependent MM-patients were enrolled into this retrospective analysis. The study population comprised patients diagnosed between 2004 and 2015 in whom an attempt to collect auto-HSC was made (68%: women, median age: 56). Patients received granulocyte-colony stimulating factor (G-CSF) alone or in combination with chemotherapy and autologous peripheral blood stem cells (auto-PBSCs) were collected by leukapheresis. RESULTS AND CONCLUSIONS: The success rate in terms of obtaining sufficient number of CD34(+) cells/kg for an auto-HSCT (≥2 × 106 cells/kg body weight) during the first mobilization attempt was 92% (26/28 patients), and for 2 auto-HSCTs (≥4 × 106 cells/kg) - was 75% (21/28 patients). After the second mobilization attempt (undertaken in 8 patients), a sufficient number of CD34(+)/kg cells for an auto-HSCT was obtained for all patients and the number of CD34(+)/kg collected cells was sufficient for 2 auto-HSCT in 6 additional patients. Hematologic toxicity and infections were the most frequent complications. Higher doses of cytarabine (>1.6 g/m2 ) and cyclophosphamide (> 2 g/m2 ) should be avoided in MMDD patients due to toxicity. Further studies are needed to establish mobilization regimens, confirm their safety, and dosing in MMDD patients.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Antígenos CD34/análise , Feminino , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Polônia , Diálise Renal , Estudos Retrospectivos , Transplante AutólogoRESUMO
Atypical chronic myeloid leukaemia (aCML) belongs to the group of myelodysplastic/myeloproliferative neoplasms. Changing diagnostic criteria and the rarity of the disease, with incidence approximately 100-times lower than the incidence of BCR-ABL1-positive chronic myeloid leukaemia, result in limited knowledge on aCML. At present the diagnosis is made based on the presence of granulocytic lineage dysplasia and precisely defined quantitative peripheral blood criteria, after exclusion of other molecularly defined myeloid neoplasms. Distinctive cytogenetic and molecular changes for aCML are missing, although recently SETBP1 mutations were described in a significant proportion of patients. The majority of patients are male and elderly. The prognosis of aCML patients is very bad, with median overall survival ranging between 10.8 and 25 months, and acute myeloid leukaemia-free survival amounting to approximately 11 months. No treatment recommendations can be made based upon current evidence, although allogeneic haematopoietic stem cell transplantation seems to be able to induce long-term remission in eligible patients.
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Background: Patients with blood disorders colonized with antibiotic-resistant bacteria (ARB) are prone to systemic infections that are difficult to treat. Reintroduction of commensal bacteria in a murine model of enterococcal colonization of the gut can lead to eradication of enterococci. We hypothesized that fecal microbiota transplantation (FMT) could be used to eradicate ARB in humans. Methods: Participants colonized with ARB were treated with intraduodenal FMT according to a prospective protocol (NCT02461199). The primary endpoint was complete ARB decolonization at 1 month after FMT. Secondary endpoints included safety assessment and partial ARB decolonization. Microbiome sequencing was performed to investigate the influence of microbial composition of the transplanted material on the outcome of FMT. Results: Twenty-five FMTs were performed in 20 participants (including 40% who had neutropenia) who were colonized by a median of 2 (range, 1-4) strains of ARB. The primary endpoint was reached in 15/25 (60%) of the FMTs and more frequently in cases in which there was no periprocedural use of antibiotics (79% vs 36%, P < .05). Among participants, 15/20 (75%) experienced complete ARB decolonization. There were no severe adverse events, and partial ARB decolonization was observed in 20/25 (80%) of the FMTs. The microbiota composition analysis revealed higher abundance of Barnesiella spp., Bacteroides, and Butyricimonas and greater bacterial richness in the fecal material, resulting in eradication of Klebsiella pneumoniae compared with nonresponders. Conclusions: FMT in patients with blood disorders is safe and promotes eradication of ARB from the gastrointestinal tract. Clinical Trials Registration: NCT02461199.
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Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Doenças Hematológicas/terapia , Adulto , Idoso , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/estatística & dados numéricos , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Multiple myeloma is a plasma cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow and associated organ damage. Usually, patients with myeloma present with a single monoclonal protein in serum and/or urine constituted by one heavy chain and one light chain. In less than 5% of the patients, more than one monoclonal protein can be identified. The aim of our retrospective multicenter matched case-control study was to describe the characteristics of cases with biclonal myeloma and compare them against a control group of monoclonal myeloma patients matched by age, sex, and year of diagnosis. A total of 50 previously untreated cases with biclonal myeloma and 50 matched controls with monoclonal myeloma were included in this study. The controls were matched (1:1) for age, sex, year of diagnosis, and participating center. There were no differences in the rates of anemia (52 vs. 59%; p = 0.52), renal dysfunction (36 vs. 34%; p = 0.83), hypercalcemia (9 vs. 16%; p = 0.28), or presence of lytic lesions (23 vs. 16%; p = 0.38) between groups. Similarly, there was no difference in the rates of overall response to therapy (85 vs. 90%; p = 0.88) or survival rates of cases with biclonal myeloma and controls with monoclonal myeloma (4-year survival 72 vs. 76%; p = 0.23). Results of our study suggest that patients with biclonal myeloma have similar response and survival rates than patients with monoclonal myeloma.
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Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Fatores Etários , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Estudos Retrospectivos , Fatores Sexuais , Taxa de Sobrevida , Fatores de TempoRESUMO
The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists. All slides were rated by at least 3 panel members (median 8 panel members; range 3-9). Marrow slides from 98 out of 105 patients were of good quality and therefore could be rated properly according to the WHO 2001 classification, including assessment of dysplastic lineages. The agreement between the reviewers whether the diagnosis was MDS or non-MDS was strong with an intra-class correlation coefficient (ICC) of 0.85. Six cases were detected not to fit the entry criteria of the registry, because they were diagnosed uniformly as CMML or AML by the panel members. The agreement by WHO 2001 classification was strong as well (ICC = 0.83). The concordance of the assessment of dysplastic lineages was substantial for megakaryopoiesis and myelopoiesis and moderate for erythropoiesis. Our data show that in general, the inter-observer agreement was high and a very low percentage of misdiagnosed cases had been entered into the EUMDS registry. Further studies including histomorphology are warranted.
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Citodiagnóstico/métodos , Síndromes Mielodisplásicas/diagnóstico , Variações Dependentes do Observador , Sistema de Registros/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Exame de Medula Óssea/métodos , Exame de Medula Óssea/normas , Citodiagnóstico/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVES: The epidemiology of myelodysplastic syndromes (MDS) differs among countries. Here, we present the first epidemiological indices determined for Poland. METHODS: Twenty-one haematological centres participated in the study. Patients diagnosed with MDS and acute myeloid leukaemia (AML) with 20-29% blasts were enrolled. Data collection was conducted for strictly predefined period. RESULTS: The overall crude incidence rate for all MDS subtypes was 1.95 (95% CI, 1.81-2.09) per 100 000 person-years: 2.46 (95% CI, 2.24-2.69) for males and 1.47 (95% CI, 1.31-1.65) for females; after excluding AML cases, the indices were as follows: 2.35 (95% CI, 2.08-2.66) for males and 1.27 (95% CI, 1.08-1.5) for females. Prevalence rate was 6.2 per 100 000 persons (95% CI, 5.96-6.45), that is 6.86 (95% CI, 6.49-7.24) for males and 5.58 (95% CI, 5.26-5.92) for females. Both incidence and prevalence increased with increasing age. The most frequently diagnosed MDS subtype was refractory cytopenia with multilineage dysplasia (RCMD), responsible for 30.3% of all newly diagnosed MDSs. CONCLUSIONS: RCMD is the most frequent MDS subtype in Poland. Incidence and prevalence indices are lower than those reported for other populations, which probably results from inadequate diagnosis of potential cases of this disease.
Assuntos
Erros de Diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Vigilância da População , Prevalência , Fatores Sexuais , Adulto JovemRESUMO
Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients. The present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend toward higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs. 34%; P = .19), which did not lead to improved median overall survival, which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (P = .64). However, DAC appeared to be superior in the group of patients aged 60-65 (CR rate: DAC 51% vs. DA 29%; P = .02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (P = .02). No differences in hematological and nonhematological toxicity between the DA and DAC regimens were observed.
Assuntos
Cladribina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/farmacologia , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Quimioterapia de Indução/métodos , Cariotipagem , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Polônia , Indução de RemissãoRESUMO
We compared the outcomes of multiple myeloma (MM) patients aged 21-40 and 41-60 years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high-risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0·001). Five- and 10-year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0·001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0·001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21-40 years, treated in the era of novel agents have a better OS than their counterparts aged 41-60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM.
Assuntos
Fatores Etários , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Adulto , Estudos de Casos e Controles , Aberrações Cromossômicas , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias , Taxa de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto JovemRESUMO
The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575-580, 2016. © 2016 Wiley Periodicals, Inc.