Fanconi anemia (FA), a rare autosomal recessive disease, frequently evolves to bone marrow failure and acute myeloid leukemia, and BMT is the treatment of choice for patients with FA. However, their ...exquisite hypersensitivity to DNA cross-linking agents is associated with severe complications and several investigators have been looking for the ideal preparatory regimen. We have been involved in a program of progressively decreasing doses of cyclophosphamide (CY) as conditioning therapy, in an attempt to identify the lowest dose of CY capable of maintaining the graft with minimum complications. Here, we describe our experience of allogeneic BMT offered to 16 patients with FA and an HLA-compatible sibling donor, conditioned with 100 mg/kg of CY. The actuarial survival is 88% at approximately 37 months. Mucositis >/= grade II was the most common complication (94%), followed by bacteremias (38%). Veno-occlusive disease and hemorrhagic cystitis did not occur. Sustained engraftment was obtained in 94% of patients, and acute and chronic GVHD was diagnosed in 13% and 7%, respectively. The lowest dose of CY for transplant in FA patients is yet to be determined, but further reductions seem possible.
Autopsy files of 180 patients were reviewed, who died after BMT between July 1987 and June 1998 and 58 (32.2%) cases, who had experienced intracranial hemorrhage (ICH) were selected. Age, sex, ...underlying disease, preparatory regimens, immunoprophylaxis, chronic and acute GVHD, survival of the patients and localization and size of hemorrhages were evaluated. There were 33 males and 25 females, with a mean age of 23.4 years. The main underlying disorders for which BMT was performed included SAA (n = 21), CML (n = 13) and AML (n = 10). Forty patients were found to have intraparenchymal hemorrhage, 35 had subarachnoid hemorrhage and eight patients had subdural hemorrhage. In 16 cases the CNS hemorrhage was so extensive that it was considered to be the main cause of death. There was no significant statistical difference concerning sex (P = 0.217), age (P = 0.296), underlying disease (P= 0.352), preparatory regimens (P = 0.07), immunoprophylaxis (P = 0.914), chronic and acute graft-versus-host disease (P = 0.107 and P = 0.631, respectively) and survival (P = 0.701) when comparing patients with or without ICH. However, the number of cases in which the CNS was defined as the main cause of death was higher among patients with ICH than in patients without ICH (n = 16 vs 15) (P = 0.011). We conclude that ICH is common and has a significant mortality rate following BMT.
Since the first successful transplantation of umbilical-cord blood in a patient with Fanconi's anemia,
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cord blood has been used as a source of hematopoietic stem cells for transplantation to treat ...a variety of malignant and nonmalignant hematologic disorders.
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Cord-blood banks have developed worldwide.
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Eurocord, a group of physicians, was organized to standardize methods of collecting, testing, and cryopreserving cord blood from both related and unrelated donors; to study the properties of cord-blood cells; and to manage a registry of cord-blood transplantation performed in Europe.
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We analyzed 143 cord-blood transplantations performed from October 1, 1988, through December 31, 1996, . . .
Fanconi Anemia (FA) is a rare and challenging disease to manage, and there is a substantial gap between treatments available in high- versus low- and middle-income countries. Although hematopoietic ...cell transplantation (HCT) is the only curative treatment for the hematological complications related to this disease, this procedure is highly complex, requiring sophisticated infrastructures and trained personnel.
Describe the outcomes after matched related, unrelated and haploidentical HCT for 216 FA patients in aplastic phase in Curitiba, Brazil.
The median age was 9-years (range: 3-32); all patients were in aplastic phase and received bone marrow as the stem cell source. 1st group: Matched Related Donors (MRD): 101 pts were transplanted between 1999-2021. Median follow-up: 9.6 years; 83 received HCT from matched siblings while 18 had other MRD. All patients received a simple preparatory regimen with Cyclophophamide (CY) 60 mg/kg with (n = 12) or without rabbit-ATG (n = 89) and GVHD-prophylaxis with cyclosporine and methotrexate (csa + MTX;96%) or mycophenolate (csa+MMF;4%). Six patients had primary or secondary graft failure (GF), all received a 2nd transplant, and 5 are alive and engrafted. Eight patients died at a median of 545 days after transplant (range: 3- 6271). Two-year transplant-related-mortality (TRM):4%. 10-year overall survival (OS) was 94%, and all patients transplanted in the past ten years are alive (n = 42). This regimen was well tolerated with a low TRM and acute and chronic GVHD incidence. 2nd group: Unrelated donors:75pts were transplanted between 2003-2021; median follow-up:6-years. HLA-compatibility: 10/10 (n = 68) and 9/10 (n = 7). 73% of donors were found in the Brazilian donor registry. All patients received a non-irradiation regimen including CY 60 mg/kg + Fludarabine + ATG, and the majority received csa + MTX as GVHD prophylaxis. GF was observed in two patients, and one is alive and well after a 2nd transplant.15pts died at a median of 117 days post-HCT (range: 3-4379), and infections were the major cause of death in 60% of patients. The day-100 CI of acute GVHD and 2-year CI of chronic GVHD was 17% and 25%, respectively. 5-year OS was 79%. 3rd group: Haploidentical donors:40pts were transplanted between 07/2013 to 01/2022, 31 patients received a preparatory regimen with Fludarabine + TBI (200) + rabbit-ATG, and 9 received Fludarabine + TBI(200) + Campath. GVHD prophylaxis with post-transplantation cyclophosphamide (PTCy) 50-60 mg/kg (total dose) + csa + MMF. Three patients in the ATG group had primary or secondary GF, received a 2nd haplo-PTCy transplant, and died. The CI of day-100 acute GVHD was 27%. The 2-year CI of chronic GVHD was 51% for the ATG group and 25% for the Campath group (p = 0.15). Six patients died at a median of 209 days due to rejection (n = 3) or GVHD (n = 3). 3-year OS was 85%. All patients in the Campath group are alive.
These results show the feasibility of performing HCT for patients with FA in aplastic phase in Brazil. This experience also reflects more than 40 years of dedication to the treatment of FA and is based on strong national and international collaborations. These simple but effective preparatory regimens can lead to excellent outcomes, serve as a guideline, and be reproducible in other countries with similar resources.
O uso da citometria de fluxo multiparamétrica (CFM) de 4 cores para o diagnóstico e seguimento de pacientes (pcts) com neoplasias hematológicas foi estratégico para evolução do conhecimento nesta ...área nas últimas duas décadas. Entretanto, o refinamento da pesquisa da Doença Residual Mínima/Mensurável (DRM) nas leucemias agudas (LA) tornou necessárias medidas para aumentar a sensibilidade e especificidade do método anteriormente utilizado.
Implantar e padronizar um método de alta sensibilidade e custo-efetivo para o diagnóstico e acompanhamento de pacientes adultos ou pediátricos com leucemias agudas num centro terciário.
Estudo de coorte prospectivo longitudinal que incluiu pcts consecutivos com diagnóstico ou seguimento de leucemias agudas (LLA-B, LLA-T e LMA) atendidos pelos serviços de hematologia, hematopediatria e transplante de medula óssea do CHC-UFPR em Curitiba, Paraná, Brasil, entre janeiro/2019 e maio/2022. Foram excluídos da análise leucemia promielocitica aguda e doenças hematológicas crônicas. Este estudo foi aprovado pelo Comitê de Ética - CAAE 84969718.0.000.0096. O consentimento para o uso de material biológico e acesso aos registros médicos foi dado pelo paciente ou guardiões legais.
O presente projeto foi realizado no âmbito do PRONON - Programa Nacional de Apoio à Atenção Oncológica, do Ministério da Saúde, que forneceu os equipamentos, reagentes e anticorpos monoclonais para a realização da DRM, conforme painéis propostos pelo grupo Euroflow. A execução financeira foi feita pela AAHC.
Para reduzir a variabilidade em todas as fases de coleta de amostras, processamento, aquisição de dados e análise, o estudo foi iniciado após reuniões educacionais com as equipes clínicas e técnicas da instituição. As amostras de medula óssea foram processadas dentro das primeiras 24 horas após a coleta. Na primeira fase foi feita implantação da técnica de lise total (bulky-lise) para as amostras com baixa celularidade; na segunda fase foram implantados os painéis de 8 cores para diagnóstico de leucemias agudas conforme proposto pelo grupo Euroflow, além da padronização do citômetro de fluxo FACS Lyric™. Na terceira fase foram validados os tubos de 8 cores para pesquisa da DRM LLA-B (Theunissen et al, 2017), DRM LLA-T e DRM LMA.
Em 40 meses foram obtidas 788 amostras/224 pcts, sendo 104 amostras de diagnóstico (46LLA-B; 52LMA; 8LLA-T), 484 amostras seguimento em diversos momentos pós quimioterapia, 43 DRM pré-TMO e 157 DRM pós-TMO.Na fase de implantação da bulky-lise demonstramos que a maioria das amostras alcançou a sensibilidade/LOD/LOQ menor que 0,001% (mais de 5.000.000 de eventos obtidos), e o uso do citômetro de fluxo de 8-10 cores foi padronizado no setor. Entre as crianças com diagnóstico de LLA, 46 (85,1%) fizeram a avaliação do D15; 42 (77,8%) d33 e 41 (75,9%) fizeram análise da semana 12; entre os pacientes com LMA a maioria realizou ao menos 2 avaliações pós quimioterapia. Os pacientes que foram submetidos ao TCTH foram seguidos para avaliação da cinética de recuperação pós transplante, e analisados em estudo específico.
A utilização dos recursos do PRONON permitiu a renovação do parque tecnológico do laboratório, como consequência houve uma melhoria evidente na pesquisa de Doença Residual Mínima, com aumento da sensibilidade e especificidade do teste em relação ao método de citometria de 4 cores. Além disso foi possível a capacitação de profissionais na área de hematologia e citometria de fluxo, com discussão dos aspectos técnico científicos e acompanhamento dos resultados, permitindo melhoria substancial no cuidado aos pacientes com leucemias agudas atendidos pelo SUS.
Background: Central nervous system fungal infections (FI) are important
complications and a cause of mortality in patients who receive
hematopoietic stem cell transplantation (HSCT). Aims: To study ...the
clinical aspects of fungal encephalitis (FE). Settings and Design: The
study was carried out at the HSCT Center of the Hospital de
Clνnicas, Federal University of Paranα, Curitiba, Brazil.
Materials and Methods: Clinical records and autopsy reports from
patients submitted to HSCT with a diagnosis of FE. Results: Twelve
patients were diagnosed with FE presenting with lowered level of
consciousness, hemiparesis and seizures. We were able to identify two
subgroups regarding susceptibility to FE: (1) patients with early onset
FI and severe leucopoenia, and (2) patients with later onset FI with
graft-versus-host disease using immunosuppressive drugs. Eleven of the
patients died directly due to the neurological complication, all had
post-mortem confirmation of the diagnosis of FI. Conclusions: These
clinical, paraclinical and temporal patterns may provide the
opportunity for earlier diagnosis and interventions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Severe aplastic anemia (sAA) is a bone marrow failure disorder which is mostly a consequence of immunologically mediated stem cell destruction. Allogeneic bone marrow transplantation (BMT) from a ...compatible donor provides long-term survival in 60 to 80% of sAA patients. However, graft rejection still remains a major problem, and a second allograft is an alternative for these patients. We retrospectively analyzed 34 patients who received a second BMT (BMT2), nine with primary graft failure (PGF) and 25 with transient engraftment (TE). The probability of survival at 13 years among PGF patients was 22% vs 60% for the TE group (P = 0.0068). Age (<17 vs>17 years), number of mononuclear cells (<3 vs >3 x 10(8)/kg) and year of transplant (1986-1991 vs 1992-1998) at BMT2 had no statistical influence on survival. A significant survival advantage was noted among TE patients (P = 0.0068), which was probably because of a longer intertransplant interval (>90 days). Furthermore, 90% of patients with positive blood cultures at BMT2 did not survive the procedure. We conclude that early detection of primary graft failure (PGF), followed by measures attempting to promote hematopoietic recovery (eg use of growth factors, further infusion of stem cells) may decrease mortality.
Background: Adenovirus-associated hemorrhagic cystitis (HC) has become a recognized sequel of immunosuppression. The diagnosis of viral infection is usually determined by viral cultures.
Objectives: ...Analysis of different diagnostic methods for adenovirus (AdV) detection in bone marrow transplant patients with hemorrhagic cystitis.
Study design: We describe a prospective study for AdV detection in the urine of patients with hematuria in the first 100 days after bone marrow transplant (BMT), comparing different laboratory techniques, PCR, enzyme immunoassay (EIA) and conventional culture.
Results: A total of 143 urine samples were analyzed, 75 collected in the pre-transplant period with and without hematuria and 68 post-transplant, only with microscopic or macroscopic hematuria. After BMT, hematuria occurred in 38.9% of patients, being more frequent in unrelated donor transplants. AdV was isolated in one pre-transplant patient without symptoms and in three post-transplant patients with HC grades 3 and 4 (severe), who were in month 2 or 3 post-transplant. Compared to culture as the gold standard, the accuracy, specificity and sensitivity of EIA were 95, 30 and 100% and for PCR were 63, 100 and 60%, respectively.
Conclusions: We concluded that despite technical difficulties and the long time that elapsed before results were obtained, cell culture still remains the best method for adenovirus detection in the urine of patients with hemorrhagic cystitis.
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