RESUMEN
Autologous stem cell transplantation (ASCT), intensifying anti-leukemic effects without significant treatment-related mortality (TRM), is particularly appealing in AML with favorable genetic/molecular profile. This study retrospectively evaluated the outcomes of post-remission treatment in consecutive favorable-risk AML patients. Sixty-six patients were included: 32 had mutated NPM1/wild-type FLT-ITD, 16 had t(8:21) and 18 - inv(16). Forty patients received chemotherapy alone, 26 underwent ASCT upfront. In time-dependent analysis, the ASCT group demonstrated higher relapse-free (RFS) (p = .001) and overall survivals (OS) (p = .0007). The 1-year RFS and OS were 44.2% vs 88% and 71% vs 96% for chemotherapy and ASCT, respectively. The corresponding TRM was 4/40 (10.0%) and 0/26 (0%), with relapse rates of 70.0% and 19.2% (p = .0002). In multivariate analysis, ASCT was associated with superior OS and RFS. In conclusion, ASCT offers significantly superior RFS and OS in favorable-risk AML in first complete remission. These data support the recent resurgence of interest in ASCT for AML.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Anciano , Terapia Combinada , Manejo de la Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Quimioterapia de Inducción , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiología , Masculino , Persona de Mediana Edad , Nucleofosmina , Pronóstico , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
AIMS: To determine the prevalence and incidence of HPA antigens and antibodies in the Israeli population and to evaluate the degree of awareness to F/NAIT in Israel. BACKGROUND: In fetal/neonatal alloimmune thrombocytopenia (F/NAIT) the fetus suffers from thrombocytopenia mediated by maternal IgG antibodies directed against fetal platelets leading to intracranial hemorrhage (ICH) in about 20% of cases. The antibodies are directed against Human Platelet Antigens (HPA). Diagnosis of F/NAIT is essential because thrombocytopenia may recur and worsen in subsequent pregnancies; hence awareness of F/NAIT is crucial. METHODS: We conducted a retrospective analysis of cases referred to the platelet immunology laboratory between the years 2011-2015 and medical records of newborns born at Rambam Medical Center during 2010-2015. RESULTS: Of the 322 cases studied, 175 (54.35%) had anti-platelet antibodies. The most common antibody was anti-HPA1a (41.85%) followed by anti-HPA5b (28.75%). The prevalence of HPA antigens was similar to that of the Caucasian population. About 80% of the cases were referred due to neonatal thrombocytopenia, found in a random blood count or after bleeding, and 13% of cases were referred due to suspected ICH during pregnancy. In only 22.6% of cases, the diagnosis was made immediately after birth, and 18.7% of the suspected cases were referred only during the subsequent pregnancy. About 84% of infants with severe thrombocytopenia were not referred to F/NAIT diagnosis. CONCLUSIONS: The prevalence of platelet antigens in the Israeli population is similar to that of the Caucasian population. The paucity of referrals points to the need to establish diagnostic guidelines and raise awareness among caregivers.
Asunto(s)
Trombocitopenia Neonatal Aloinmune , Femenino , Feto , Humanos , Lactante , Recién Nacido , Israel , Embarazo , Prevalencia , Estudios Retrospectivos , Trombocitopenia Neonatal Aloinmune/diagnóstico , Trombocitopenia Neonatal Aloinmune/epidemiologíaRESUMEN
In fetal/neonatal alloimmune thrombocytopenia (FNAIT), platelets are destroyed by maternal antibodies directed against fetal/neonate antigens. Thrombocytopenia can be severe and lead to intracranial hemorrhage (ICH) in about 10% of cases. Although three types of antigen groups, presented on platelets [ABO blood group antigens, human leukocyte antigens (HLA) and human platelet antigens (HPA)] are known to be implicated in immune platelet destruction, antibodies against HPA are most commonly involved in FNAIT and hence are the target of extensive research. Awareness of FNAIT by physicians as well as the availability of the most sensitive diagnostic methods capable of detecting a wide range of antibodies are crucial for the diagnosis of FNAIT and the prevention of severe thrombocytopenia and its bleeding risks in subsequent pregnancies.
Asunto(s)
Antígenos de Plaqueta Humana/inmunología , Plaquetas/patología , Trombocitopenia Neonatal Aloinmune/diagnóstico , Trombocitopenia Neonatal Aloinmune/inmunología , Sistema del Grupo Sanguíneo ABO/análisis , Sistema del Grupo Sanguíneo ABO/inmunología , Anticuerpos/análisis , Anticuerpos/inmunología , Antígenos de Plaqueta Humana/análisis , Plaquetas/inmunología , Antígenos HLA/análisis , Antígenos HLA/inmunología , Humanos , Recién Nacido , Trombocitopenia Neonatal Aloinmune/patologíaRESUMEN
Nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (HSCT) is a rare phenomenon usually associated with graft-versus-host disease (GVHD). This systematic review of post-HSCT NS cases reported in the literature aimed to identify risk factors and unique features of the disease in this clinical setting. One hundred sixteen cases of post-HSCT NS published in the English literature between 1988 and 2015 were revealed and analyzed. The median onset of NS was 20.5 months (range, 3 to 174) post-HSCT. NS development was associated with acute or chronic GVHD in 87.2% of cases. Membranous nephropathy (MGN) was the most frequent pathology (65.5%), followed by minimal change disease (MCD) (19%). Complete remission of the NS was achieved in 63.5% of patients (59.1% of MGN cases and 81.3% of MCD cases; P = .15). Patients presenting with MCD recovered at a median of 1.75 months (range, 1 to 12) and with MGN a median of 7 months (range, 1 to 53) (P = .001). NS was treated with corticosteroids alone in 16.8% of patients and with a combination of corticosteroids and other immunosuppressive agents in 73.5% of patients. Univariate analysis failed to identify a single predictive factor of response to therapy. In conclusion, post-HSCT NS usually develops concomitant to GVHD and is associated with high rates of response to therapy. Although most patients were treated with a combination of immunosuppressive drugs, single-agent therapy with steroids may be sufficient in some cases.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Nefrótico/etiología , Adulto , Enfermedad Injerto contra Huésped/patología , Humanos , Inmunosupresores/uso terapéutico , Riñón/patología , Síndrome Nefrótico/tratamiento farmacológico , Pronóstico , Adulto JovenRESUMEN
BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are emerging. In attempt to eradicate CRE colonization, we conducted a semirandomized, prospective, controlled trial using oral nonabsorbable antibiotics. METHODS: Consecutive hospitalized CRE carriers were studied. Patients whose rectal isolates were gentamicin sensitive but colistin resistant were treated with gentamicin. Patients whose isolates were colistin sensitive but gentamicin resistant were treated with colistin. Patients whose isolates were sensitive to both drugs were randomized to 3 groups of oral antibiotic treatment: gentamicin, colistin, or both. Patients whose isolates were resistant to both drugs, and those who did not consent, were followed for spontaneous eradication. RESULTS: One hundred fifty-two patients were included; 102 were followed for spontaneous eradication for a median duration of 140 days (controls), and 50 received 1 of the 3 drug regimens: gentamicin, 26; colistin, 16; both drugs, 8, followed for a median duration of 33 days. Eradication rates in the 3 treatment groups were 42%, 50%, and 37.5%, respectively, each significantly higher than the 7% spontaneous eradication rate in the control group (P < .001, P < .001, and P = .004, respectively) with no difference between the regimens. No significant adverse effects were observed. CONCLUSION: Oral antibiotic treatment with nonabsorbable drugs to which CRE is susceptible appears to be an effective and safe for eradication of CRE colonization and, thereby, may reduce patient-to-patient transmission and incidence of clinical infection with this difficult-to-treat organism.
Asunto(s)
Antibacterianos/administración & dosificación , Portador Sano/tratamiento farmacológico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Resistencia betalactámica , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Heces/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Administration of intensive chemotherapy used in the management of malignancies is accompanied with marrow suppression. Patients undergoing such treatments and especially those with acute leukemia need prolonged blood component support and are at risk for platelet (PLT) refractoriness. Irradiated and filtered blood, although effective, does not eliminate the risk for refractoriness and consequent fatal hemorrhage. STUDY DESIGN AND METHODS: The current report presents a case of an acute myeloid leukemia patient who became alloimmunized to multiple HLA antigens after complicated autologous stem cell transplantation and to whom granulocytes were transfused as part of treatment for overwhelming sepsis. Poor engraftment necessitated prolonged transfusion dependency with rare HLA-compatible donors detected according to the indirect PLT immunofluorescence test. During the proceeding weeks the patient suffered from recurrent severe attacks of gastrointestinal bleeding. When several conservative treatments failed, a fully HLA-matched, bidirectionally ABO-incompatible allogeneic transplantation from a sibling donor was performed. RESULTS: Allogeneic transplantation was uneventful, with stable full donor-derived lymphohematopoietic engraftment. CONCLUSION: Immune PLT refractoriness can appear at later stages of treatment even in severely immunocompromised patients. Granulocyte transfusions could lead to alloimmunization and should therefore be cautiously considered in this patient population.
Asunto(s)
Incompatibilidad de Grupos Sanguíneos/terapia , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas , Isoanticuerpos/sangre , Leucemia Mieloide Aguda/terapia , Transfusión de Plaquetas , Adulto , Biomarcadores/sangre , Incompatibilidad de Grupos Sanguíneos/diagnóstico , Incompatibilidad de Grupos Sanguíneos/inmunología , Femenino , Granulocitos/trasplante , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/inmunología , Sepsis/etiología , Sepsis/terapia , Trasplante HomólogoRESUMEN
The use of allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) was almost abandoned in recent years for very effective targeted therapy with tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including SCT. 38 consecutive CML patients were treated (most in preimatinib era) with allogeneic SCT, using partial T cell depletion (TCD) and preemptive donor lymphocyte infusion (DLI), without post-transplant graft-versus-host disease (GvHD) prophylaxis. Conditioning included busulfan, cyclophosphamide, antithymocytic globulin, and fludarabine followed by donor stem cell transfusion. With a median follow up of 90.5 months (1-134), 32 patients are alive. 97% engrafted. 5-year leukemia free survival (LFS) and overall survival (OS) were 78.95% and 84.2%, respectively. All patients are in major molecular remission and 78% in complete molecular remission. Transplant-related mortality (TRM) was 13%. Twenty-four patients received DLI for residual disease. Acute GvHD, mostly Grades I-II, occurred in 18% of patients post-transplant and in 24% of patients receiving DLI. In conclusion, the risk-adapted approach using only partial TCD and preemptive escalated dose of DLI precluded the need for immunosuppressive medications and reduced the risk of significant GvHD without compromising engraftment and long-term disease control. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Depleción Linfocítica , Transfusión de Linfocitos , Trasplante de Células Madre de Sangre Periférica/métodos , Acondicionamiento Pretrasplante/métodos , Adulto , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Depleción Linfocítica/métodos , Transfusión de Linfocitos/métodos , Masculino , Persona de Mediana Edad , Riesgo , Linfocitos T/efectos de los fármacos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/terapia , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/terapia , Resultado Fatal , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Persona de Mediana Edad , Trasplante HomólogoRESUMEN
In an attempt to abrogate the deleterious effects of graft-versus-host disease (GVHD), allogeneic transplantation for nonmalignant diseases was performed using high-dose CD34-cell infusion, partial T cell depletion, and no posttransplantation GVHD prophylaxis. Between 1998 and 2004, 16 patients with matched related donors were treated. Median age was 1.5 years (range, 5 months-18 years). The conditioning regimen consisted of busulphan 16 mg/kg, cyclophosphamide 200 mg/kg, antithymocyte globulin (ATG) 25 mg/kg, and fludarabine 200 mg/m(2). No GVHD prophylaxis was given. High doses of CD34 cells, positively selected by immunomagnetic beads, were infused at a median dose of 10.7 x 10(6) CD34/kg (range, 7.4-50 x 10(6)). A total of 1 x 10(5)/kg T cells were given. All patients engrafted, with no graft rejections. All were alive and well at a median of 37 months posttransplantation (range, 18-89 months). Only 1 patient developed chronic GVHD. No episodes of severe infection occurred during or after transplantation. Immunologic reconstitution with CD3/CD4 T cells > 200/microL was observed at a median of 117 days and that with naive T cells (CD4/CD45RA) at a median of 188 days posttransplantation. Our findings suggest that allogeneic transplantation from a matched family donor for nonmalignant disorders can be successfully performed using high doses of CD34 cells, moderate T cell depletion, and no posttransplantation immunosuppression.
Asunto(s)
Trasplante de Médula Ósea/métodos , Enfermedad Injerto contra Huésped/prevención & control , Depleción Linfocítica/métodos , Adolescente , Antígenos CD34 , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Sistema Inmunológico/citología , Lactante , Masculino , Estudios Retrospectivos , Tasa de Supervivencia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Resultado del TratamientoRESUMEN
In this retrospective study, the hemorrhagic and thrombotic events are reported at presentation and during induction in 34 consecutive acute promyelocytic leukemia (APL) patients treated in a single referral center. The most consistent hemostatic abnormality was decreased fibrinogen level (<150 mg/dL) found in 21 patients (61%), partial thromboplastin time (PTT) was normal almost in all patients. A mildly prolonged prothrombin time (PT) was observed in 14 patients (44%). Median platelet count was 30.10(9)/L (range 3-191.10(9)/L). Life-threatening bleeding manifestations occurred in 10 patients (29%). By multivariate analysis, severe bleeding complications did not correlate with hemostatic parameters but did correlate with white cell count at presentation. Four patients (12%) had severe thrombotic events, two cerebral sagital sinus thrombosis, one pulmonary embolism, and one subclavian vein thrombosis. Two other patients had pseudotumor cerebri. Three out of six patients with thrombotic events were found to have thrombophilia. These results may suggest an association between thrombophilia and thrombosis in APL patients. Two patients suffered from combined severe bleeding and thrombosis. Hemostatic parameters are not helpful in predicting neither hemorrhage nor thrombosis.
Asunto(s)
Antineoplásicos/efectos adversos , Hemorragia/etiología , Leucemia Promielocítica Aguda/complicaciones , Valor Predictivo de las Pruebas , Trombosis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Pruebas de Coagulación Sanguínea , Femenino , Fibrinógeno/análisis , Hemorragia/diagnóstico , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Retrospectivos , Factores de Riesgo , Trombofilia/complicaciones , Trombosis/diagnósticoRESUMEN
Stem cell transplantation preceded by reduced-intensity conditioning (RIC) is based on the use of immunosuppressive agents as the sine qua non to ensure donor cell engraftment. It is a curative option for select patients suffering from haematological and non-haematological malignancies. The most beneficial results are observed when a full donor engraftment is achieved with 'tolerable' graft-vs-host disease (GVHD). To date, a vast amount of clinical data has been published, but in an uncontrolled manner. This review summarizes the currently known outcome of allogeneic transplants with RIC, with every disease category analysed separately. Unresolved problems include the optimal combination of immunosuppressive agents, the degree of infectious complications, and GVHD that may appear in some patients. Directions to overcome these complications are discussed. Despite the paucity of controlled clinical data, the current indications for RIC allogeneic transplantation are summarized based on the best-available phase II data.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/métodos , Pronóstico , Acondicionamiento Pretrasplante/efectos adversos , Trasplante HomólogoRESUMEN
Between March 1997 and January 2002, 18 consecutive patients (18-47 years) with hematological malignancies and previous proven invasive fungal infection underwent stem cell transplantation (SCT) (10 matched sibling allograft, 6 autograft, and 2 haploidentical). All patients had full myeloablative conditioning. The fungal pathogens diagnosed were Aspergillus (14), Fusarium (2), Mucor (1), Exserohilum (1), and Candida (1), involving the lungs (15), sinuses (5), and liver (1). All patients were treated pre- and during transplant with systemic antifungal therapy. Eleven out of 18 (61%) patients survived the transplant. Only 1 of 5 patients who transplanted with an active fungal infection accompanied with active leukemia survived the transplant, compared with 10/13 (84%) survivals in patients who had no clinical and radiological signs of infection or active leukemia (P < 0.025). None of the autografted patients has died, compared with 7/12 allografted patients, of whom 5 underwent transplant with active hematological/active fungal disease. In only 3 patients was the cause of death reactivation of previous fungal infection. Both active fungal infection and active leukemia place patients at a very high risk for procedure-related mortality. Pre-transplant therapy of fungal infection, aiming to achieve a clinically undetectable state of infection, followed by an antifungal treatment during transplant may allow the SCT with no fungal reactivation in selected patients.