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1.
Haematologica ; 109(3): 765-776, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37199126

RESUMO

Androgens represent the historical therapeutic backbone of bone marrow failure (BMF) syndromes. However, their role has rarely been analyzed in a prospective setting, and systematic and long-term data regarding their usage, effectiveness and toxicity in both acquired and inherited BMF are currently unavailable. Here, taking advantage of a unique disease-specific international dataset, we retrospectively analyzed the largest cohort so far of BMF patients who received androgens before or in the absence of an allogeneic hematopoietic cell transplantation (HCT), re-evaluating their current use in these disorders. We identified 274 patients across 82 European Society for Blood and Marrow Transplantation (EBMT) affiliated centers: 193 with acquired (median age 32 years) and 81 with inherited (median age 8 years) BMF. With a median duration of androgen treatment of 5.6 and 20 months, respectively, complete and partial remission rates at 3 months were 6% and 29% in acquired and 8% and 29% in inherited disorders. Five-year overall survival and failure-free survival (FFS) were respectively 63% and 23% in acquired and 78% and 14% in inherited BMF. Androgen initiation after second-line treatments for acquired BMF, and after >12 months post diagnosis for inherited BMF were identified as factors associated with improved FFS in multivariable analysis. Androgen use was associated with a manageable incidence of organ-specific toxicity, and low rates of solid and hematologic malignancies. Sub-analysis of transplant-related outcomes after exposure to these compounds showed probabilities of survival and complications similar to other transplanted BMF cohorts. This study delivers a unique opportunity to track androgen use in BMF syndromes and represents the basis for general recommendations on this category of therapeutics on behalf of the Severe Aplastic Anemia Working Party of the EBMT.


Assuntos
Anemia Aplástica , Humanos , Adulto , Criança , Anemia Aplástica/terapia , Androgênios , Medula Óssea , Estudos Prospectivos , Estudos Retrospectivos , Transtornos da Insuficiência da Medula Óssea
2.
J Transplant ; 2023: 8865364, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37810405

RESUMO

Pakistan is the fifth most populous country with a population of 225 million and has health expenditure accounting for only 2.8 percent of gross domestic product (GDP). Accordingly, there are a limited number of haematology-oncology and transplant centers in the country. The Pakistan Blood and Marrow Transplant (PBMT) group was established in 2020, and this report is the first activity survey from January 2021 to December 2022 focusing on the trends of matched-related donor, haploidentical, and autologous transplants in a developing country. A total of 12 transplant centers contributed data on the modified PBMT survey form retrospectively and 806 haematopoietic stem cell transplants (HSCTs) were carried out during the study duration. Allogeneic HSCT constituted 595 (73.8%) of all the transplants; this is in stark contrast to Western data, where autologous HSCT accounts for the majority of transplants. ß-thalassemia major and aplastic anemia were the commonest indications for allogeneic HSCT, in contrast to Western data, where acute leukemia is the leading transplant indication. Autologous transplants were more frequently performed for Hodgkin's lymphoma as compared to non-Hodgkin's lymphoma and multiple myeloma. The use of peripheral and bone marrow stem cells was comparable. A myeloablative conditioning regimen was routinely used in patients with acute leukemia. This report provides an insight of HSCT trends in Pakistan which are different from those of Western centers contributing to transplant data from South Asia.

5.
Transplant Cell Ther ; 27(3): 274.e1-274.e5, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33781541

RESUMO

Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients.


Assuntos
Anemia Aplástica , Anemia de Diamond-Blackfan , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Anemia de Diamond-Blackfan/terapia , Medula Óssea , Criança , Humanos , Estudos Retrospectivos
6.
Blood Rev ; 47: 100772, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33187812

RESUMO

Treatment options for newly diagnosed aplastic anemia (AA) patient includes upfront allogeneic hematopoietic stem cell transplant (HSCT) or immunosuppressive therapy (IST). With recent advances in supportive care, conditioning regimens and post-transplant immunosuppression the overall survival for HSCT approaches 70-90%. Transplant eligibility needs to be assessed considering age, comorbidities, donor availability and probability of response to immunosuppressive therapy (IST). Upfront HSCT should be offered to children and young adults with matched related donor (MRD). Upfront HSCT may also be offered to children and young adults with rapidly available matched unrelated donor (MUD) who require urgent HSCT. Bone marrow (BM) graft source and cyclosporine (CsA) plus methotrexate (MTX) as graft versus host disease (GVHD) prophylaxis are preferable when using anti-thymocyte globulin (ATG) based conditioning regimens. Alemtuzumab is an acceptable alternative to ATG and is used with CsA alone and with either BM or peripheral blood stem cells (PBSC). Cyclophosphamide (CY) plus ATG conditioning is preferable for patients receiving MRD transplant, while Fludarabine (Flu) based conditioning is reserved for older adults, those with risk factors of graft failure and those receiving MUD HSCT. For haploidentical transplant, use of low dose radiotherapy and post-transplant cyclophosphamide has resulted in a marked reduction in graft failure and GVHD.


Assuntos
Anemia Aplástica/terapia , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Terapia de Imunossupressão , Condicionamento Pré-Transplante , Fatores Etários , Aloenxertos , Soro Antilinfocitário/uso terapêutico , Ciclosporina/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Fatores de Risco , Doadores não Relacionados , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
7.
Biol Blood Marrow Transplant ; 26(12): 2245-2251, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32717437

RESUMO

Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Anemia Aplástica/terapia , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adulto Jovem
8.
J Coll Physicians Surg Pak ; 30(5): 527-531, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32580853

RESUMO

OBJECTIVE: To compare the efficacy and side effect profile of different bortezomib-based triplet regimens for remission induction in patients with multiple myeloma (MM). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Armed Forces Bone Marrow Transplant Centre, Rawalpindi from January 2014 to December 2018. METHODOLOGY: A total of 81 patients of MM, were registered from January 2014 to December 2018. In final analysis, 44 out of 81 patients were included as per inclusion/exclusion criteria. Bortezomib-based regimens were used either as first line (in newly diagnosed) or as second line (in relapsed/refractory bortezomib naïve patients) therapy. Three different bortezomib-based triplet therapies were used (1) VCd, (2) VRd and (3) VTd. As there were only two patients in VTd regimen group so for study purposes VRd and VTd were grouped together, i.e. Vd with an IMiD. Response to treatment was assessed using the IMWG criteria. Comparison between different bortezomib-based regimens was performed in terms of their tolerability and response rate after four cycles of chemotherapy. RESULTS: Out of 44 patients, 79.5% (n=35) patients received bortezomib-based triplet regimen as first line therapy, and in 20.5% (n=9) patients as second line therapy. VCd was administered to 56.8% (n=25) and Vd with an IMiD was used in 43.1% (n=19, VRd in 17 and VTd in 2) of the patients. Response was assessed at the end of fourth cycle. Overall response rate was comparable in both groups, 88% in VCd versus 89.4% in Vd with an IMiD group (p=0.432). In VCd and Vd with an IMiD group, CR was observed in 52% (n=13) and 57.9% (n=11) patients, respectively. Disease remained stable in 6.8% (n=3) patients. Treatment was generally well tolerated. Comparative analyses of both treatment groups revealed that the frequency of peripheral neuropathy was significantly higher in Vd with an IMiD group (47.3% vs 8% p=0.03). Grade III/IV neuropathy observed in 15.7% (n=3) of the patients in Vd with an IMiD group vs none in VCd group. Grade III/IV cytopenias were more seen in VCd group then in Vd with an IMiD group (16% vs. 5.2% p=0.16). CONCLUSION: The overall response rates were comparable in VCd and Vd with IMiD, with a better side effect profile seen with VCd regimen. Key Words: Multiple myeloma, Bortezomib, Triplet therapy, Remission induction, Peripheral neuropathy.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Indução de Remissão , Talidomida/uso terapêutico , Resultado do Tratamento
9.
Bone Marrow Transplant ; 55(7): 1485-1490, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32024988

RESUMO

Hematopoietic Stem Cell Transplantation (HSCT) is the only potentially curative treatment option for the hematologic complications that occur in patients with Fanconi anemia (FA). In this study, we present a retrospective multicenter analysis from the Eastern Mediterranean Blood and Marrow Transplantation Group (EMBMT) of matched related donor HSCT for FA in adolescents and adults transplanted between 1988 and 2015. Forty-five patients received HSCT with a median age at transplant of 18 years, the interquartile range (IQR) (15-23.5); 25 (55.6%) patients were females and 20 (44.4%) were males. Conditioning regimen was fludarabine-based in 29 (64.4%) patients, irradiation-based in five (11.1%) patients, and the remaining patients received other combinations. Indication for HSCT was bone marrow failure in 39 (86.7%) and myelodysplastic syndrome in six (13.3%) patients. Stem cell source was bone marrow in 22 (48.9%), peripheral blood in 20 (44.4%), umbilical cord blood in one (2.2%), and combination of bone marrow and cord blood in two (4.4%) patients. Twenty-seven (60%) patients engrafted and five (11.1%) had primary engraftment failure. The median time to neutrophil engraftment was 14 days (range 10-21 days); median time for platelet engraftment was 17 days (10-33 days). The probability of developing grade II-IV acute GVHD for all patients was 7.0% and chronic GVHD 36.6%. No new malignancies were reported. The OS probability was 53.6% (95% CI, 38.3-68.9%) with a median follow-up of 13 months (95% CI, 1-240). Our HLA-matched related HSCT results in AYA patients with FA compare favorably with other reported international registry data.


Assuntos
Anemia de Fanconi , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Medula Óssea , Anemia de Fanconi/terapia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Condicionamento Pré-Transplante
10.
Hematology ; 25(1): 48-54, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31906834

RESUMO

Objective: Prevalence of aplastic anemia (AA) is high in the Asian population. This study was done to explore the etiology and association of AA with various socio-economic and environmental factors.Study design and setting: Study included 1324 consecutive AA cases registered at Armed Forces Bone Marrow Transplant Centre Rawalpindi, Pakistan, from March 2001 to August 2016. The study questionnaire was completed through an interview. It included patients' socio-demographic details, personal and family medical history, environmental attributes and clinico-hematological features.Results: The median age of patients was 20 years, 997 were male and 327 female. Distribution of non-severe, severe and very severe AA was 230 (17.4%); 598 (45.2%) and 496 (37.4%), respectively. The majority of patients were from low (n = 761, 57.5%) or middle socioeconomic class (n = 543, 41%). Consanguinity among patients (n = 806, 61%) was slightly higher than the national statistics. History of chemical exposures included fertilizers (n = 116, 8.7%), pesticides (n = 56, 4.2%) and industrial chemicals (n = 37, 2.8%). PNH clone was found in 63 of AA patients. After excluding 298 patients undergoing HSCT and 660 deaths/lost to follow-up, disease evolution was observed in 38(10.4%) patients out of 366 evaluable patients. These included PNH = 18, MDS = 11 and AML = 9.Discussion: Due to lack of funding and adequate human resource at the center, age and sex-matched controls could not be included. Other limitations were a lack of molecular testing to exclude the possibility of inherited bone marrow failure syndromes on a genetic basis.Conclusion: Younger age, male predominance and higher consanguinity point toward genetic factors in AA etiology among the South Asian population.


Assuntos
Anemia Aplástica/epidemiologia , Adolescente , Adulto , Fatores Etários , Anemia Aplástica/induzido quimicamente , Anemia Aplástica/genética , Criança , Pré-Escolar , Consanguinidade , Poluentes Ambientais/efeitos adversos , Feminino , Fertilizantes/efeitos adversos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Praguicidas/efeitos adversos , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
11.
Congenit Anom (Kyoto) ; 60(1): 32-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30809872

RESUMO

Fanconi anemia (FA) is a recessive disorder that predispose to bone marrow failure and multiple congenital anomalies in affected individuals worldwide. To date, 22 FA genes are known to harbor sequence variations in disease phenotype. Among these, mutations in the FANCA gene are associated with 60% to 70% of FA cases. The aim of the present study was to screen FA cases belonging to consanguineous Pakistani families for selected exons of FANCA gene which are known mutational hotspots for Asian populations. Blood samples were collected from 20 FA cases and 20 controls. RNA was extracted and cDNA was synthesized from blood samples of cases. DNA was extracted from blood samples of cases and ethnically matched healthy controls. Sanger's sequencing of the nine selected exons of FANCA gene in FA cases revealed 19 genetic alterations of which 15 were single nucleotide variants, three were insertions and one was microdeletion. Of the total 19 sequence changes, 13 were novel and six were previously reported. All identified variants were evaluated by computational programs including SIFT, PolyPhen-2 and Mutation taster. Seven out of 20 analyzed patients were carrying homozygous novel sequence variations, predicted to be associated with FA. These disease associated novel variants were not detected in ethnically matched controls and depict genetic heterogeneity of disease.


Assuntos
Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Anemia de Fanconi/genética , Mutação/genética , Adolescente , Criança , Análise Mutacional de DNA , Anemia de Fanconi/epidemiologia , Anemia de Fanconi/patologia , Feminino , Genótipo , Homozigoto , Humanos , Íntrons/genética , Masculino , Paquistão/epidemiologia
12.
Clin Hematol Int ; 2(2): 82-91, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34595447

RESUMO

Allogeneic stem cell transplant for high-risk aplastic anemia (AA) yields inferior results using conventional cyclophosphamide (CY)-based conditioning. The use of fludarabine (Flu)-based regimens has resulted in improved outcomes in high-risk patients. Limited data are available comparing these two conditioning regimens in such patients. We retrospectively analyzed 192 high-risk patients undergoing matched-related donor transplantation from July 2001 to December 2018. The median age was 19.5 (2-52) years. Patients were divided into 2 groups, Cy200 anti-thymocyte globulin (ATG)20 (Gp1 n = 79) or Flu120-150 Cy120-160 ATG20 (Gp2 n = 113). The risk of graft failure was significantly higher in Gp1, and the majority occurred in patients with >2 risk factors (p = 0.02). The incidence of grade II-IV acute graft versus host disease (GVHD) and chronic GVHD was not significantly different between the two groups. The overall survival (OS) of the study cohort was 81.3 %, disease-free survival (DFS) 76.6 % and GVHD-free relapse-free survival (GRFS) was 64.1%. DFS and GRFS were significantly higher in Gp2 as compared to Gp1: DFS 84.1% versus 68.4 % (p = 0.02), GRFS 77.9% versus 54.4% (p = 0.01), respectively. We conclude that Flu-based conditioning is associated with superior OS, DFS and GRFS as compared to the conventional Cy-based regimen in high-risk AA.

13.
Biol Blood Marrow Transplant ; 25(12): 2375-2382, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31394274

RESUMO

Despite excellent transplant outcomes of aplastic anemia (AA) in developed countries, management in developing countries is challenging because of delay in the diagnosis, use of family donors for transfusions, and higher infection risk pretransplant. These factors can lead to allo-immunization, increased risk of graft failure, graft-versus-host disease (GVHD), and transplant-related mortality, leading to unfavorable outcomes. Conventional cyclophosphamide (Cy) and antithymocyte globulin (ATG) are associated with inferior overall survival in such high-risk patients. We conducted single-center retrospective analysis of high-risk AA patients (N = 147) enrolled consecutively and undergoing matched related donor transplant from March 2002 through October 2018. We included high-risk AA patients receiving fludarabine (Flu)-based conditioning. Median patient age was 20 years (range, 3 to 52). The median time from diagnosis to transplant was 11 months (range, 3 to 63). High-risk features included age ≥ 20 years in 55.8% of patients (n = 82), disease duration more than 3 months in 95 % (n = 140), RBC concentrates transfusions > 20 in 79.6% (n = 117), random donor platelet transfusion > 50 in 64.6% of patients (n = 95), and second hematopoietic stem cell transplant (HSCT) in 7.4% (11). We divided patients into 2 groups based on different conditioning regimens. Flu group 1 (Flu1) received Flu 120 to 150 mg/m2, Cy 120 to 200 mg/kg, and ATG 20 mg/kg, and Flu group 2 (Flu2) was given Flu 150 mg/m2, Cy 300 mg/m2, and ATG 20 mg/kg. Bone marrow stem cells were used as graft source in 97% of patients (n = 144) (alone in 52% and with peripheral blood stem cells in 45%). Cyclosporine alone was used for GVHD prophylaxis in 75% (n = 110) and cyclosporine plus methotrexate in 25% (n = 37). Median total nucleated cell dose was 5 × 108/kg. Median days for neutrophil engraftment was 13 (range, 10 to 20) and platelet engraftment 20 (range, 14 to 43). Day 100 mortality was 7.5% (n = 11). Sustained successful engraftment was achieved in 87.8% of patients (n = 129). Most graft failures (40%) occurred in Flu2 conditioning (P = .000) and in patients with >2 risk factors (P = .000). Overall incidence of acute and chronic GVHD was 11.6% (n = 17) and 12.9% (n = 19), respectively, in Flu1 and Flu2 groups. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) was 83.7%, 78.2%, and 70.7%, respectively. A trend toward improved OS was observed in patients receiving Flu1 conditioning but was statistically nonsignificant (P = .256), whereas DFS and GRFS were significantly better in Flu1 versus Flu2 (P = .004 and .001, respectively). When stratified per number of risk factors (age > 20, RBC concentrate > 20 or platelet > 50 random, duration > 3 months, previous HSCT), OS and DFS decreased significantly with increasing number of risk factors (P = .000 and .001, respectively). Patients are able to tolerate Flu-based conditioning well with lower rates of rejection and excellent long-term survival in high-risk AA patients. Cyclosporine alone as GVHD prophylaxis and marrow source stem cells as graft source are preferable options. Use of Flu plus low-dose Cy conditioning is associated with inferior survival outcomes. A randomized trial of Flu-based versus conventional Cy-containing conditioning would be helpful in establishing a standard of care conditioning regimen in high-risk AA patients.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adolescente , Adulto , Aloenxertos , Anemia Aplástica/mortalidade , Anemia Aplástica/terapia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Vidarabina/administração & dosagem
14.
Clin Case Rep ; 7(7): 1442-1444, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31360508

RESUMO

Post-transplant lymphoproliferative disorders are rare but potentially life-threatening complication of HSCT. Although not frequently reported but PTLD can occur as a late post-transplant complication in HSCT recipients. A high index of suspicion should be kept for early diagnosis of these disorders as delay in diagnosis can have catastrophic implications.

15.
Hematol Oncol Stem Cell Ther ; 12(3): 127-132, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30653940

RESUMO

BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) are often referred for physical therapy (PT) to help improve their quality of life. However, to our knowledge there is no clear PT pathway to guide therapists and patients before, during, and after HSCT. METHODS: A comprehensive literature review was carried out exploring the role and benefits of PT in HSCT patients. The current evidence was comlimented with recommendations and opinions from the experts in the field, which included PT's and hematology consultants from PTAGVHD and the EMBMT group. RESULT: A clear pathway and protocol as a working guide for rehabilitation professionals working with the HSCT patient's was developed. CONCLUSION: This paper not only reviews the current evidence on safe PT practice but also puts forward a protocol and pathway for HSCT rehabilitation, highlights the importance of individualized exercise intervention for HSCT patients, and outlines safe practice guidelines for the physical therapists working in this field.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Modalidades de Fisioterapia , Qualidade de Vida , Transfusão de Sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Aptidão Física , Contagem de Plaquetas
16.
Ann Hematol ; 98(2): 301-312, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30426156

RESUMO

Aplastic anemia (AA) is the most serious non-malignant blood disorder in Pakistan, ranked second in prevalence, after thalassemia. We investigated various epidemiological, clinical, and genetic factors of AA in a Pakistani cohort of 214 patients reporting at our hospital between June 2014 and December 2015. A control group of 214 healthy subjects was included for comparison of epidemiological and clinical features. Epidemiological data revealed 2.75-fold higher frequency of AA among males. A single peak of disease onset was observed between ages 10 and 29 years followed by a steady decline. AA was strongly associated with lower socioeconomic profile, rural residence, and high rate of consanguineous marriages. Serum granulocyte colony-stimulating factor and thrombopoietin levels were significantly elevated in AA patients, compared to healthy controls (P < 0.0001), while there was no statistical significance in other nine cytokine levels screened. Allele frequencies of DRB1*15 (56.8%) and DQB1*06 (70.3%) were predominantly high in AA patients. Ten mutations were found in TERT and TERC genes, including two novel mutations (Val526Ala and Val777Met) in exons 3 and 7 of TERT gene. Despite specific features of the AA cohort, this study suggests that epidemiologic and etiologic factors as well as host genetic predisposition exclusively or cooperatively trigger AA in Pakistan.


Assuntos
Anemia Aplástica , Mutação de Sentido Incorreto , Adolescente , Adulto , Idade de Início , Substituição de Aminoácidos , Anemia Aplástica/sangue , Anemia Aplástica/epidemiologia , Anemia Aplástica/genética , Criança , Feminino , Frequência do Gene , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos/genética , Cadeias beta de HLA-DQ/sangue , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/sangue , Cadeias HLA-DRB1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Fatores Sexuais , Fatores Socioeconômicos , Telomerase/sangue , Telomerase/genética , Trombopoetina/sangue , Trombopoetina/genética
17.
J Glob Oncol ; 4: 1-13, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30521413

RESUMO

Use of haploidentical (haplo) donors for hematopoietic cell transplantation (HCT) has significantly increased in the last decade. The major advantage with this strategy is universal availability and faster acquisition of the donor, along with affordability and provision of immunotherapy in post-transplantation period. Historically, haplo-HCT was associated with compromised outcomes because of high rates of graft-versus-host disease and graft failure, but after the development of a post-transplantation high-dose cyclophosphamide strategy, which results in selective T-cell depletion, these issues have been addressed to a large extent. Nevertheless, graft failure, high treatment-related mortality due to graft-versus-host disease, infections, delayed immune reconstitution, and disease relapse remain significant concerns. As the experience with haplo-HCTs grows, the clinical outcomes are becoming more at par with those seen with fully matched unrelated donor allogeneic HCTs.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/métodos , Humanos
18.
J Coll Physicians Surg Pak ; 28(6): S89-S90, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29866231

RESUMO

Primary myelofibrosis (PMF) is a clonal, BCR-ABL1 negative myeloproliferative neoplasm characterised by splenomegaly, leukoerythroblastic peripheral blood picture and bone marrow fibrosis. Different cytogentic abnormalities are documented in PMF which have impact on clinical outcome and overall survival. Del 5q31 is documented in only 0.8% of PMF patients and is associated with poor outcome and increased risk of progression to acute leukemia. Anemia with del 5q responds frequently to lenalidomide treatment. We are reporting case of a middle-aged male who presented with constitutional symptoms, myelofibrosis; and calreticulin type 2 mutation was present. His cytogenetics showed del 5q positivity. He was started on lenalidomide but developed toxic epidermal necrolysis, resultantly lenalidomide was stopped. Skin eruptions are a known entity in patients with lenalidomide therapy; but to date, there is no reported case of lenalidomide induced toxic epidermal necrolysis (TEN) in patients with myelofibrosis.


Assuntos
Anemia Macrocítica , Calreticulina/metabolismo , Deleção Cromossômica , Fatores Imunológicos/efeitos adversos , Lenalidomida/efeitos adversos , Mielofibrose Primária/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Cromossomos Humanos Par 5 , Citogenética , Humanos , Fatores Imunológicos/uso terapêutico , Lenalidomida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/diagnóstico
19.
J Ayub Med Coll Abbottabad ; 30(Suppl 1)(4): S647-S651, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30838824

RESUMO

BACKGROUND: Patients with haematological malignancies and stem cell transplant recipients are at high risk of opportunistic infections. Little international and no national data is available comparing noble metal coated versus uncoated central venous catheters (CVC) in this special population of severely immunocompromised patients. Objective of the study is to compare infectious and non-infectious complications of noble metal coated versus uncoated central venous catheters in patients undergoing stem cell transplantation and receiving chemotherapy for acute myeloid leukaemia. METHODS: This is a prospective, cross-sectional, randomized study (January to December 2016), enrolling 45 consecutive patients undergoing stem cell transplantation or chemotherapy for acute myeloid leukaemia. Patients were randomized in 2 groups. Twenty 23 patients received standard CVC and 22 patients received CVC catheters coated with three noble metals (Gold, Silver, Palladium). Patients were observed for catheter related infectious and noninfectious complications. Data was analysed using SPSS. RESULTS: Mean age was 24.3 (±4.91) in uncoated and 25.09 (±5.22) in coated CVL group. CRBSI infection was detected in 2 (8.6%) and 3 (13.6%) patients in uncoated and coated group respectively with p-value of .279. There was no statistically significant difference in febrile episodes between coated (95.4%) and uncoated (91.3%) group. While we considered non-infectious complications, 2 patients in coated (8.6%) and 1 in uncoated CVCs group (4.3%) had CVC thrombosis which was not significant statistically. CONCLUSION: There was no efficacy of BG-thin noble metal coated CVCs in reducing infectious and non-infectious complications (thrombosis) in our study.


Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Cateteres de Demora/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Hospedeiro Imunocomprometido , Metais , Adulto , Antineoplásicos/uso terapêutico , Estudos Transversais , Desenho de Equipamento , Feminino , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
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