RESUMO
Granulomatous amebic encephalitis (GAE) is a rare, nearly always fatal form of encephalitis that occurs mostly in the setting of immune compromise or chronic disease. The prevalence and clinical characteristics of this Acanthamoeba infection in hematopoietic stem cell transplant (HSCT) recipients are not well described. We present an HSCT patient in whom the diagnosis of GAE was made at autopsy. A systematic review of previously reported cases is provided to highlight the clinical presentation and early diagnostic features of GAE in HSCT recipients. Amebic infection usually initially involves the skin or lungs over a period of months, and becomes rapidly fatal once it crosses the blood-brain barrier. GAE is usually discovered postmortem owing to lack of awareness of this deadly infection and delay in diagnosis. Subacute presentation of multiple recurrent panniculitis-like subcutaneous nodules associated with eosinophilia and a history of chronic rhinitis or sinusitis warrant investigation for a possible amebic infection. Prolonged corticosteroid use and a recent exposure to unhygienic water are potential risk factors for GAE. Successful outcomes may be achieved with early intensive treatment using a combination of effective drugs.
Assuntos
Acanthamoeba/isolamento & purificação , Amebíase/diagnóstico , Encéfalo/parasitologia , Encefalite/diagnóstico , Granuloma/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Amebíase/parasitologia , Amebíase/patologia , Animais , Autopsia , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/diagnóstico , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Encefalite/parasitologia , Encefalite/patologia , Evolução Fatal , Feminino , Granuloma/parasitologia , Granuloma/patologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-IdadeRESUMO
Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (<24 months), and to identify factors predicting for early vs late relapses (24-48 months post-AHCT). Over three periods (2001-2004, 2005-2008, 2009-2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35-38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky <90, stage III, >1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.
Assuntos
Mieloma Múltiplo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoglobulina A/metabolismo , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Recidiva , Transplante Autólogo/métodos , Adulto JovemRESUMO
The optimum graft-versus-host disease (GVHD) management in today's clinical practice remains controversial. There is an enormous heterogeneity among transplanters in their therapeutic decisions for each individual patient with GVHD. Existing guidelines do not always cover many unique clinical scenarios. Consequently, a significant number of allograft recipients fail either because of severe GVHD or relapse of underlying malignancy. Until more effective methods are available, tailoring the current GVHD management by modification of immunosuppressive therapy in each patient based on disease and transplant characteristics may decrease the mortality. The purpose of this review is to raise several questions among readers about GVHD management and generate new hypotheses, which may need to be tested in cooperative group studies.
Assuntos
Doença Enxerto-Hospedeiro/terapia , Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/uso terapêuticoRESUMO
PURPOSE: To evaluate the long-term outcome after allogeneic (allo) and autologous (auto) blood or marrow transplantation (BMT) in patients with relapsed or refractory Hodgkin's lymphoma (HL). PATIENTS AND METHODS: We analyzed the outcome of 157 consecutive patients with relapsed or refractory HL, who underwent BMT between March 1985 and April 1998. Patients Assuntos
Transfusão de Sangue
, Transplante de Medula Óssea
, Doença de Hodgkin/terapia
, Adolescente
, Adulto
, Baltimore
, Criança
, Intervalo Livre de Doença
, Feminino
, Doença Enxerto-Hospedeiro
, Doença de Hodgkin/mortalidade
, Humanos
, Estudos Longitudinais
, Masculino
, Pessoa de Meia-Idade
, Recidiva
, Análise de Sobrevida
, Transplante Autólogo
, Transplante Homólogo
, Resultado do Tratamento
RESUMO
Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 10(8) per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/efeitos adversos , Estadiamento de Neoplasias , Disfunção Primária do Enxerto/tratamento farmacológico , Disfunção Primária do Enxerto/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Neoplasias Meníngeas , Segunda Neoplasia Primária , Sarcoma Mieloide , Neoplasias Cutâneas , Adolescente , Adulto , Idoso , Aloenxertos , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/terapia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/terapia , Sarcoma Mieloide/mortalidade , Sarcoma Mieloide/terapia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapiaRESUMO
Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Programas de Rastreamento , Segunda Neoplasia Primária/diagnóstico , Feminino , Humanos , Masculino , Segunda Neoplasia Primária/epidemiologia , Especificidade de Órgãos , Fatores de RiscoRESUMO
Alternative donor transplantation is increasingly used for high-risk lymphoma patients. We analyzed 1593 transplant recipients (2000-2010) and compared transplant outcomes in recipients of 8/8 allele HLA-A, -B, -C and DRB1 matched unrelated donors (MUDs; n=1176), 7/8 allele HLA mismatched unrelated donors (MMUDs; n=275) and umbilical cord blood donors (1 or 2 units UCB; n=142). Adjusted 3-year non-relapse mortality of MMUD (44%) was higher as compared with MUD (35%; P=0.004), but similar to UCB recipients (37%; P=0.19), although UCB had lower rates of neutrophil and platelet recovery compared with unrelated donor groups. With a median follow-up of 55 months, 3-year adjusted cumulative incidence of relapse was lower after MMUD compared with MUD (25% vs 33%, P=0.003) but similar between UCB and MUD (30% vs 33%; P=0.48). In multivariate analysis, UCB recipients had lower risks of acute and chronic GVHD compared with adult donor groups (UCB vs MUD: hazard ratio (HR)=0.68, P=0.05; HR=0.35; P<0.001). Adjusted 3-year OS was comparable (43% MUD, 37% MMUD and 41% UCB). These data highlight the observation that patients with lymphoma have acceptable survival after alternative donor transplantation. MMUD and UCB can extend the curative potential of allotransplant to patients who lack suitable HLA matched sibling or MUD.
Assuntos
Antígenos HLA , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Linfoma/mortalidade , Linfoma/terapia , Doadores não Relacionados , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Aloenxertos , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de SobrevidaRESUMO
Diarrhea is a difficult diagnostic problem in patients with chronic graft-versus-host disease (cGVHD) because there are many causes of it. Although intestinal involvement has been reported in early studies of untreated cGVHD, this is now a very rare presentation of the disease. In addition to other etiologies, pancreatic insufficiency should also be considered in patients with cGVHD who demonstrate malabsorption. The pathogenesis of pancreatic insufficiency in these patients is unknown. Pancreatic enzyme supplements can be very effective in treating this rare condition.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas/terapia , Pancreatopatias , Adulto , Pré-Escolar , Doença Crônica , Diarreia/diagnóstico , Diarreia/etiologia , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Masculino , Pancreatopatias/diagnóstico , Pancreatopatias/etiologia , Pancreatopatias/fisiopatologiaRESUMO
We prospectively studied absolute lymphocyte (ALC) and monocyte counts (AMC), lymphocyte subsets and proliferative in vitro responses to mitogen and antigen in 12 patients with AL-amyloidosis (AL) undergoing autologous blood stem cell transplantation (SCT) with high-dose i.v. melphalan. Myeloid and lymphoid recovery (>500 per microl) occurred in a median of 10 days post SCT. While there was a continuous decline in the number of CD4+ T cells at 3 months, ALC, AMC, B cells (CD19+), CD8+ T cells, and NK cells (CD16+/56+) returned to baseline. While T cell proliferative responses to phytohemagglutinin (PHA) remained depressed, B cell function measured by the proliferative response to staphylococcal antigen returned to baseline by 3 months. To supplement our findings, we retrospectively evaluated ALC, AMC and serum immunoglobulin levels in a separate group of patients treated with the same protocol at our institution. ALC and AMC recovery was similar to the pattern observed in the initial study group. Immunoglobulin levels remained within normal ranges at 3 and 12 months after SCT. Of 50 patients who were followed for a minimum of 1 year following SCT, seven (14%) developed shingles and one (2%) had PCP pneumonia. In conclusion, cellular immune function, reflected by absolute numbers of CD4+ T cells and PHA responsive T cell proliferation, is significantly suppressed at 3 months after SCT in patients with AL, and this post-transplant immunosuppression is associated with a low but clinically meaningful occurrence of opportunistic infections typical of T cell immunosuppression.
Assuntos
Amiloidose/imunologia , Amiloidose/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Amiloidose/sangue , Feminino , Humanos , Imunoglobulinas/sangue , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante AutólogoRESUMO
Relapse remains a major cause of treatment failure after autotransplantation (auto-PBSCT) for Hodgkin's disease (HD). The administration of non-crossresistant therapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after auto-PBSCT in 37 patients with relapsed or refractory HD. Patients received high-dose gemcitabine-BCNU-melphalan and auto-PBSCT followed by involved-field radiation and up to four cycles of the DCEP-G regimen, which consisted of dexamethasone, cyclophosphamide, etoposide, cisplatin, gemcitabine given at 3 and 9 months post transplant alternating with a second regimen (DPP) of dexamethasone, cisplatin, paclitaxel at 6 and 12 months post transplant. The probabilities of event-free survival (EFS) and overall survival (OS) at 2.5 years were 59% (95% CI=42-76%) and 86% (95% CI=71-99%), respectively. In all, 17 patients received 54 courses of CC and 15 were surviving event free (2.5 years, EFS=87%). There were no treatment-related deaths during or after the CC phase. Post-transplant CC is feasible and well tolerated. The impact of this approach on EFS should be evaluated in a larger, randomized study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Terapia de Salvação/métodos , Adolescente , Adulto , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Dexametasona/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/mortalidade , Prevenção Secundária , Análise de Sobrevida , Transplante Autólogo , GencitabinaRESUMO
BACKGROUND: Myocardial ischemia induced by 5-fluorouracil (5-FU) is a relatively rare, but potentially serious, occurrence. Some case reports have indicated that recurrent ischemia may be prevented if 5-FU is resumed after pretreatment with antianginal therapy. METHODS: A 54-year old woman was diagnosed with stage IIA squamous cell carcinoma of the anus. Treatment with concurrent radiation and chemotherapy (mitomycin-C and 5-FU) was initiated with curative intent. RESULTS: The patient had no evidence of underlying coronary artery disease based on history, physical examination or ECG. Approximately 48 h after initiation of 5-FU infusion the patient developed anginal pain associated with ECG changes compatible with ischemia. After resolution of ischemia and ruling out of myocardial infarction, coronary arteriography demonstrated normal coronary arteries. In an attempt to prevent myocardial ischemia, calcium channel blocker and nitrate therapy was started, but anginal pain with ECG change recurred when 5-FU was resumed. This necessitated selection of an alternative chemotherapy regimen. CONCLUSIONS: Even in the presence of normal coronary arteries, antianginal therapy may not preclude the occurrence of potentially serious 5-FU induced myocardial ischemia. For patients who experience 5-FU-induced myocardial ischemia, development of alternative chemotherapy regimens should be considered.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Fluoruracila/efeitos adversos , Isquemia Miocárdica/induzido quimicamente , Nitratos/uso terapêutico , Administração Oral , Neoplasias do Ânus/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Urinary neopterin levels, blood dihydropteridine reductase activity as well as other frequently used clinical parameters were evaluated in 110 patients suffering from various types of lymphomas and leukemias. Among them neopterin was detected as the most sensitive marker representing the severity of malignancy (p<0.00001). All patients with active diseases had significantly raised urinary neopterin levels compared to those in remission and healthy controls. Of 69 patients with active disease 66 (96%) were above the upper limit seen in healthy subjects. In addition, the highest neopterin excretion was found in patients with active chronic myeloid leukemia (1469+/-479 micromol/mol creatinine n=16). In contrast, only 1 of 41 patients in stable responsive disease and remission (2.4%) had increased urinary neopterin levels above the upper limit. Dihydropteridine reductase (DHPR) activities were also detected in all patients and control groups. In active disease slightly reduced (DHPR) activities were evident (3.42+/-0.37 for controls, 2.92+/-0.39 in active disease and 3.28+/-0.42 nmol red cytochrome C/min/5 mm diameter disc in remission patients). However in patients under medication this was strengthened. This data also suggest that DHPR activity can be effected by chemotherapy. The results of the present study support the fact that urinary neopterin levels may be an useful and reliable early prognostic marker for neoplasia when used together with other prognostic indicators. Our data also suggest that reductions in DHPR activities may also be an underlying cause for the neurological disorders that are commonly seen in patients with haematological malignancies.
Assuntos
Biomarcadores Tumorais , Di-Hidropteridina Redutase/sangue , Leucemia/sangue , Leucemia/urina , Linfoma/sangue , Linfoma/urina , Neopterina/urina , Humanos , Leucemia/fisiopatologia , Linfoma/fisiopatologia , Valor Preditivo dos Testes , PrognósticoRESUMO
To assess the impact of spleen status on engraftment, and early morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), we analyzed 9,683 myeloablative allograft recipients from 1990 to 2006; 472 had prior splenectomy (SP), 300 splenic irradiation (SI), 1,471 with splenomegaly (SM), and 7,440 with normal spleen (NS). Median times to neutrophil engraftment (NE) and platelet engraftment (PE) were 15 vs 18 days and 22 vs 24 days for the SP and NS groups, respectively (P<0.001). Hematopoietic recovery at day +100 was not different across all groups, however the odds ratio of days +14 and +21 NE and day +28 PE were 3.26, 2.25 and 1.28 for SP, and 0.56, 0.55, and 0.82 for SM groups compared to NS (P<0.001), respectively. Among patients with SM, use of peripheral blood grafts improved NE at day +21, and CD34+ cell dose >5.7 × 10(6)/kg improved PE at day+28. After adjusting variables by Cox regression, the incidence of GVHD and OS were not different among groups. SM is associated with delayed engraftment, whereas SP prior to HCT facilitates early engraftment without having an impact on survival.