ABSTRACT
Abstract Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in pa tients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.
Resumen El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RT-PCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.
Subject(s)
Humans , Middle Aged , COVID-19 , Hematology , Argentina/epidemiology , COVID-19 Testing , SARS-CoV-2ABSTRACT
Abstract We retrospectively analyzed 570 adult patients who received allogeneic stem cell transplantation for malignant diseases. The outcomes were compared according to donor type. Most of the patients (60%) were transplanted for acute leukemia. Median follow-up was 1.6 years. Haploidentical allogeneic stem cell transplantation was more frequently performed for acute myeloid leukemia and in late stages than any other donor type. Non-relapse mortality at 100 days and one year for unrelated and haploidentical donors were similar, 19%-29% vs. 17%-28%, respectively. A significant better non-relapse mortality was observed for matched sibling donors (7%-15%; p < 0.001). Relapse rate was higher in haploidentical donors compared to matched sibling and unrelated donors (three year relapse rate 46%, 39%, 28%; respectively p < 0.001). Haploidentical donors resulted in lower three year progression-free survival and worse 3 year overall survival (32%; p < 0.001 and 42%; p < 0.001) compared with other donors (44% and 55% MSD, 40% and 42% UD, respectively). The incidence of grade II-IV acute graft-versus-host disease was higher in unrelated donors (51% unrelated, 35% haploidentical, 36% matched sibling; respectively; p = 0.001), with no difference in grades III-IV (p = 0.73) or in chronic graft-versus-host disease (p = 0.2) between groups. After multivariate analysis, haploidentical and unrelated donors remained negatively associated with non-relapse mortality (HR 1.95; 95% CI 1.10-3.20 and HR 2.70; 95% CI 1.63-4.46, respectively). Haploidentical donors were associated with a higher risk of relapse and worse overall survival. This analysis shows that haploidentical donors were associated with similar non-relpase mortality and higher relapse rates than unrelated donors. Better results in non-relapse mortality were observed for matched sibling donors.
Resumen Se efectuó un análisis retrospectivo de 570 pacientes adultos que recibieron un trasplante alogénico de precursores hematopoyéticos, comparando los resultados según el tipo de donante. La mediana de seguimiento fue de 1.6 años. El 60% de la población se trasplantó por leucemias agudas. Los trasplantes haploidénticos se hicieron en su mayoría en leucemia mieloide aguda y en estadios tardíos en comparación a otros donantes. La mortalidad libre de enfermedad al día +100 y a 1 año fue similar para los donantes no emparentados y haploidénticos (19% y 29% vs. 17% y 28%, respectivamente). Se obtuvieron mejores resultados con donantes relacionados idénticos (7% y 15%; p < 0.001). La recaída fue mayor en los donantes haploidénticos (tres años 46% haploidénticos, 39% relacionados idénticos, 28% no emparentados; p < 0.003). El trasplante con donante haploidéntico presentó una menor supervivencia libre de progresión y menor supervivencia global a tres años (32%; p < 0.001 y 42%; p < 0.001). La incidencia de enfermedad injerto contra huésped aguda fue mayor en no emparentados (51%, 35% haploidénticos, 36% relacionados idénticos; p = 0.001), sin diferencias en grados III-IV (p = 0.73) o en EICH crónica (p = 0.2). Los trasplantes con donante haploidéntico y no emparentado mantuvieron su asociación negativa con mortalidad libre de enfermedad (HR 1.95; 95%IC 1.10-3.20 y HR 2.70; 95%IC 1.63-4.46), en análisis multivariado. El trasplante haploidéntico se asoció a mayor recaída y a menor supervivencia global. Esta experiencia mostró similar mortalidad libre de enfermedad entre trasplantes con donantes haploidénticos y no emparentados. Los trasplantes relacionados idénticos mostraron menores tasas de mortalidad libre de enfermedad.
Subject(s)
Humans , Adult , Hematopoietic Stem Cell Transplantation , Graft vs Host Disease , Retrospective Studies , Bone Marrow Transplantation , Disease-Free Survival , SiblingsABSTRACT
We have retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplantation (HSCT) between January 1997 and July 2013. Median follow up was 1.3 years. Sex, age, diagnosis, disease stage, comorbidities (according to HCT-CI score), type of donor, histocompatibility, conditioning regimen and graft-versus-host disease (GVHD) prophylaxis were evaluated. The incidence and severity of acute and chronic GVHD, overall survival (OS), disease free survival (DFS), non-relapse mortality (NRM) and relapse were investigated according those variables. Acute GVHD incidence was 41% (7.3% GIII-IV). Patients with acute myeloid leukemia had lesser aGVH GII-IV (14% vs. 35%, p < 0.01) comparing to the entire population. Extensive cGVHD incidence was 9.4%. Global OS 1-3 years was 44-20%, DFS 33-20%, relapse 35-41% and NRM 36-43% respectively. The presence of comorbidities showed a significant increase in NRM (CT-CI 0 vs. 1 vs ≥ 2: 1-3 years 17-24% vs. 40-46% vs. 45-67%, p = 0.001, MA HR 2.03, CI 95% 1.02-5.29), as well as cyclosporine vs. tacrolimus (1-3 years 47-53% vs. 25-36%, p = 0.01). Tacrolimus patients had higher 1-3 years OS (49-25% vs. 31-13%, p = 0.01) and DFS (41-26% vs. 20-11%, p < 0.01). Age, type of donor and myeloablative conditioning showed no significant differences in any outcome. Allogeneic HSCT is a valid therapeutic option for older patients in Argentina. The main risk factor for a significantly increased NRM and a trend to inferior OS was the number of comorbidities. Age was not a factor for a worse result. The other factor having a significant effect in better outcome was tacrolimus administration.
Se efectuó un análisis retrospectivo de 137 historias clínicas de pacientes mayores de 50 años que recibieron un trasplante alogénico de precursores hematopoyéticos (TAPH). Se evaluaron las siguientes características: sexo, edad, enfermedad, estadio, comorbilidades (según el HCT-CI), donante, acondicionamiento e inmunosupresión. Se analizó la incidencia de enfermedad injerto vs. huésped aguda (aEICH) y crónica (cEICH), supervivencia global (SG), supervivencia libre de enfermedad (SLE), recaída y mortalidad libre de enfermedad (MLE). Los trasplantes fueron realizados entre 1997-2013, mediana de seguimiento 1.3 años. La incidencia de aEICH fue de 41% (7.3% GIII-IV). Los pacientes con leucemia mieloide aguda presentaron menor incidencia de EICHa GII-IV (14% vs. 34%, p < 0.01). La incidencia de EICHc extenso fue de 9.4%. La SG a 1-3 años fue 44-20%, SLE 33-20%, recaída 35-41% y la MLE 36-43%. Los pacientes con comorbilidades tuvieron un aumento significativo de la MLE (HCT-CI 0 vs. 1 vs. ≥2: 1-3 años 17-24% vs. 40-46% vs. 45-67%, p = 0.001, AMV HR 2.03, IC 95% 1.02-5.29), al igual que el uso de ciclosporina vs. tacrolimus (1-3 años 47-53% vs. 25-36%, p = 0.01). Los pacientes que recibieron tacrolimus tuvieron una mayor SG (1-3 años 49-25% vs. 31-13%, p = 0.01) y SLE (1-3 años 41-26% vs. 20-11%, p < 0.01). La edad, tipo de donante y acondicionamiento no resultaron significativos para ningún evento. El TAPH es una herramienta terapéutica válida en pacientes mayores. Los factores pronósticos que inciden mayormente en el trasplante son las comorbilidades y no la edad. El otro factor que demostró un efecto significativo fue el uso de tacrolimus.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Hematopoietic Stem Cell Transplantation/mortality , Graft vs Host Disease/mortality , Time Factors , Retrospective Studies , Risk Factors , Age Factors , Tacrolimus/therapeutic use , Cyclosporine/therapeutic use , Graft vs Host Disease/prevention & control , Immunosuppressive Agents/therapeutic useABSTRACT
Peripheral T-cell lymphomas are a group of rare neoplasms originating from clonal proliferation of mature post-thymic lymphocytes with different entities having specific biological characteristics and clinical features. As natural killer cells are closely related to T-cells, natural killer-cell lymphomas are also part of the group. The current World Health Organization classification recognizes four categories of T/natural killer-cell lymphomas with respect to their presentation: disseminated (leukemic), nodal, extranodal and cutaneous. Geographic variations in the distribution of these diseases are well documented: nodal subtypes are more frequent in Europe and North America, while extranodal forms, including natural killer-cell lymphomas, occur almost exclusively in Asia and South America. On the whole, T-cell lymphomas are more common in Asia than in western countries, usually affect adults, with a higher tendency in men, and, excluding a few subtypes, usually have an aggressive course and poor prognosis. Apart from anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, that have a good outcome, other nodal and extranodal forms have a 5-year overall survival of about 30 percent. According to the principal prognostic indexes, the majority of patients are allocated to the unfavorable subset. In the past, the rarity of these diseases prevented progress in the understanding of their biology and improvements in the efficaciousness of therapy. Recently, international projects devoted to these diseases created networks promoting investigations on T-cell lymphomas. These projects are the basis of forthcoming cooperative, large scale trials to detail biologic characteristics of each sub-entity and to possibly individuate targets for new therapies.
Subject(s)
Humans , Hematologic Neoplasms , Killer Cells, Natural , Lymphoma, T-Cell/classification , Lymphoma, T-Cell/epidemiology , Lymphoma, T-Cell/pathology , PrognosisABSTRACT
Transplantation of hematopoietic progenitor cells (HPC) from bone marrow and mobilized peripheral blood is a standard therapy in malignant and non malignant diseases. The lack of suitable donors is an important limitation. The discovery that umbilical cord blood (CB) contains high numbers of HPC that can be used as an alternative source for allogeneic stem cell transplantation led ITMO to establish BANCEL, the first Argentine and Latinoamerican experience of its kind. The blood remaining in the umbilical cord and in the placenta was requested from women who were in the last quarter of pregnancy. An informed consent together with a medical record focused on family disease was completed. Out of 65 donations, 55 (85 per cent) were collected and 51 (78 per cent) were cryopreserved. Mean collected volume was 110 ml with 68 per cent (75 ml) reduction and mean cryopreservation of 35 ml; ABO and Rh blood group systems were determined, HLA, class I, A and B loci, and class II, DR locus were typed by molecular biology methods using PCR-SSOP. Infectious disease screening was carried out for brucellosis, syphilis, Chagas, hepatitis B and C, HIV I and II, HTLV I and II, toxoplasmosis and cytomegalovirus. Two positive units for hepatitis B (anticore) and two positive units for Chagas were discarded. The quantity of total nucleated cells (TNC), CD34+ cells and the clonogenic capacity were determined twice at the collection and after the procedures of volume reduction previous to cryopreservation. A 5 per cent reduction in both TNC and CD34 cells and a 10 per cent in the colony forming units (CFU) were detected. A good correlation coefficient between TNC and CFU was obtained.
Subject(s)
Humans , Male , Female , Pregnancy , Infant, Newborn , Blood Banks , Fetal Blood , Hematopoietic Stem Cells , Cryopreservation , Hematopoietic Stem Cell TransplantationABSTRACT
La Leucemia Mieloide Crónica (LCM) es un proceso oncohematológico caracterizado por una proliferación clonal que afecta a la célula hematopoyética primitiva. Un 95 por ciento de pacientes presenta una alteración citogenética característica conocida como Cromosoma Philadelphia (Ph1), producto de una traslocación cromosómica 9:22, que da lugar a un gen hídrido BCR/ABL. Diecinueve pacientes con LMC recibieron Trasplante Alogeneico de Médula Osea (TMO), 9 fueron de sexo femenino y 10 de sexo masculino. La média de edad fue de 32 años (rango 9-47); 15 de los pacientes estaban en fase crónica (FC) y 4 en fase acelerada (FA). Todos los pacientes al momento del diagnóstico fueron Ph1+, BCR/ABL+. El régimen de acondicionamiento consistió en Busulflán y Ciclofosfamida, con el agregado de Etoposido en los pacientes en FA. La profilaxis de EICH se efectuó con Ciclosporina A, Metotrexato y Metilprednisona en 17 pacientes y con las 2 primeras drogas en 2 pacientes. La traslocación 922 se estudió mediante técnica de RT-PCR, con empleo de las sondas NB1+, Abl3, B2A, CA3 y A2. La sensibilidad del método fue de 1 x 10(-6). De 19 pacientes que ingresaron al protocolo, 14 permanecen vivos y en remisión clínica, hematológica y citogenética (Ph, negativo); 3 pacientes fallecieron de EICH agudo, 1 de fallo de "angraftment" y 1 de síndrome urémico hemolítico. De 4 pacientes trasplantados en FA, 3 están vivos y en remisión completa. Los pacientes con LMC trasplantados presentaron una sobrevida del 74 por ciento con un seguimiento medio de 655 días. El quimerismo hematopoyético completo se demostró en 16 pacientes, mediante el estudio de 3 loci, D1S80, APO B y D17S30. No se encontró ninguna relación entre la presencia post TMO del híbrido BCR/ABL (RT.PCR) y la recaída de la enfermedad; la presencia de EICH agudo y/o crónico no tuvo influencia entre la positividad del BCR/ABL. El TMO ha demostrado se en nuestra experiencia la única alternativa terapéutica para la LMC con obtención de remisión completa, clínica, hematológica y citogenética, con una sobrevida media del 74 por ciento comparable a la de centros internacionales de trasplante.