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1.
Cytotherapy ; 25(12): 1331-1337, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37737766

RESUMO

BACKGROUND AIMS: Graft failure after allogeneic transplant for aplastic anemia is problematic. The risk of graft failure depends on multiple variables, including the preparative regimen, donor type, stem cell dose and source among other variables. METHODS: We performed a retrospective analysis of patients with aplastic anemia who underwent matched-sibling allogeneic transplant at a single center. RESULTS: We identified 82 patients who fit the inclusion criteria. One had primary graft failure and was excluded from this analysis. The recipient median age was 22 years. The donor median age was 23 years. The median time from diagnosis to transplant was 1.6 months. The median number of red cell transfusions before transplant was nine. The median number of platelet transfusions before transplant was 18. Thirteen patients developed secondary graft failure, with a cumulative incidence at 5 years of 16% and median time to develop secondary graft failure of 129 days. All patients engrafted with a median time for neutrophil engraftment of 19 days and a median time for platelet engraftment of 22 days. The survival of patients with or without secondary graft failure was not different. Major or bidirectional ABO incompatibility and older recipient age were statistically significantly associated with greater risk of secondary graft failure. CONCLUSIONS: Secondary graft failure is a significant complication after allogeneic transplant for SAA. Identification of recipients at risk and mitigating the potential risks of this complication is warranted.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto Jovem , Adulto , Anemia Aplástica/epidemiologia , Anemia Aplástica/terapia , Incidência , Estudos Retrospectivos , Irmãos , Medula Óssea , Ciclofosfamida , Fatores de Risco , Células-Tronco , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
2.
Ann Hematol ; 101(2): 421-428, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34719735

RESUMO

Priming donors with G-CSF before BM harvest is reported to improve engraftment and GvHD in recipients. These effects are highly desirable when transplanting patients with non-neoplastic hematologic diseases, particularly AA patients. Here we retrospectively report the outcomes of 39 AA patients receiving a primed BM graft from MSD to 43 patients receiving a steady-state BM graft from MSD, otherwise transplanted using a uniform transplant platform. The graft had higher TNC and CD34 cell concentrations in the primed group (p < 0.001), and that was reflected in higher TNC and CD34 doses per kilogram of recipient in the primed group (p = 0.004 and 0.03, respectively). The OS for primed BM graft recipients was 97.4% and 78.9% for the steady-state BM graft recipients, p-value = 0.01. The cumulative incidence of death without GF was 2.6% in the primed group and 16.3% in the steady-state group, p-value = 0.03. There was no difference in GvHD incidence between the two groups. We confirm that priming improved the TNC and CD34 graft concentration and cell dose; this evidence along with other reported studies constitute reasonable evidence to prove that BM priming improve engraftment. We observed no increase in GvHD using primed BM graft.


Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Adolescente , Adulto , Transplante de Medula Óssea/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Doadores de Tecidos , Resultado do Tratamento , Adulto Jovem
3.
Transplant Cell Ther ; 30(3): 312.e1-312.e7, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38185379

RESUMO

Haploidentical donor (haplo-) hematopoietic stem cell transplantation (HSCT) with post-transplantation cyclophosphamide (PTCy) is now performed on a large scale worldwide. Our patient outcomes did not completely reflect the results published by other groups. We herein present the results of 60 patients with hematologic malignancies treated homogeneously on a modified version of the standard protocol by adding ATG as an additional graft-versus-host disease (GVHD) prophylaxis measure. This was a retrospective analysis of 60 haplo-HSCT recipients using a myeloablative conditioning regimen with antithymocyte globulin and PTCy for GVHD prophylaxis. At 5 years, overall survival was 59.2%, relapse-free survival (RFS) was 48.6%, and chronic GVHD (cGVHD) and relapse-free survival was 40%. The median time to neutrophil and platelet engraftment was 16 days and 28.5 days, respectively. The rates of grade II-IV acute GVHD and extensive cGVHD were 46.7% and 23.3%, respectively. The cumulative incidence of relapse was 30%, nonrelapse mortality was 21.6%, and transplantation-related mortality was 11%. Higher Disease Risk Index and 50% HLA match were associated with lower RFS. Female donor to male recipient and older donor age were associated with an elevated risk of cGVHD. The use of PTCy might not yield the same results in different populations. Many remaining questions need to be addressed in randomized trials, including optimal graft source and donor, date of calcineurin inhibitor initiation, personalized or targeted dose of PTCy, immune reconstitution, and others.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Feminino , Humanos , Masculino , Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva Local de Neoplasia/complicações , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos
4.
Int J Hematol Oncol ; 12(1): IJH42, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36874377

RESUMO

Aim: The outcome of T-cell acute lymphoblastic leukemia (T-ALL) has improved with the use of pediatric-inspired protocols in the adolescents and young adults (AYA) population. There is limited literature regarding the outcome of T-ALL/lymphoblastic lymphoma (LBL) AYA patients treated with pediatric protocols. Methods: A total of 35 T-ALL/LBL-AYA patients ages between 14 and 55 years were treated with AYA-15 protocol. Results: At a median follow-up of 5 years the overall survival, disease-free survival and event-free survival are 71%, 62% and 49.6% respectively. Toxicities were within the expected range. Conclusion: Our single-center experience real-world data in treating T-ALL/LBL-AYA patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18-55 years.

5.
Bone Marrow Transplant ; 58(6): 680-686, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36959370

RESUMO

PGF is a devastating complication after allogeneic transplant. We retrospectively analyzed our haploidentical transplant registry to report the incidence and impact of DSA and anti-HLA on engraftment. 107 patients were identified. Median recipient-age of 22, median donor-age of 31. Sixty-two patients had AML (58%), 29 had ALL (27%), 16 (15%) had other malignancies. Sixty-one recipients (57%) had positive anti-HLA, 56 of them had the DSA results available, of these 17 patients had DSAs (15% of the total number of patients, or 28% of patients who have anti-HLA antibodies). The median cumulative MFI was 2062. Sixty-three percent of the DSA were against class-II HLA antigens. The OS, CIR, aGvHD, and cGvHD did not differ between patients with and without anti-HLA antibodies, nor between patients with and without DSA. The gender of the recipient and donor, as well as the gender mismatch between recipient and donor, were statistically associated with the incidence of anti-HLA antibodies. Three patients only developed GF (2.8%), one was primary (0.9%) and the other two secondary GF (1.9%). None of the GF cases was in patients with anti-HLA antibodies or DSA. The presence of anti-HLA or DSAs did not affect the outcomes including the incidence of PGF.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos , Incidência , Transplante de Células-Tronco Hematopoéticas/métodos , Anticorpos , Antígenos HLA , Doadores de Tecidos , Soro Antilinfocitário , Rejeição de Enxerto , Isoanticorpos
6.
Int Migr ; 60(1): 188-204, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34230681

RESUMO

During the COVID-19 pandemic, Saudi Arabia's domestic public health institutions struggle to control the COVID19 virus's spread within undocumented migrant populations, endangering both local Saudi and migrant populations. As a result, Saudi Arabia implemented a temporary amnesty policy, granting state pardon to undocumented migrants to access to health care services. Using combined qualitative fieldwork data in 2008-2009 and, more recently in 2020 among irregular Asian and African migrants' communities in Jeddah, I argue that the lack of institutional trust, combined with differential economic opportunities in Saudi and origin countries, significantly impacts undocumented migrants' decision to avoid health amnesty reform. This is particularly critical as it could likely disrupt government attempts at curbing COVID-19 within migrant communities, thus posing serious health, economic, and security threats to the Saudi state. The study contributes to empirical and theoretical debates because it highlights migrant perception's role towards local institutions in Gulf's domestic migration policymaking.

7.
Bone Marrow Transplant ; 57(4): 593-597, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35110691

RESUMO

BACKGROUND: Pediatric-inspired non-transplant regimens for adolescent and adult ALL patients are becoming standard in many institutions. We aimed to compare a cohort of patients receiving a pediatric-inspired protocol to a cohort of patients treated with adult type ALL therapy followed by allografting after achieving CR1. METHOD: Eighty-five adolescent and adult ALL patients treated with CALGB 19802 protocol who received MSD transplant in CR1 were retrospectively compared to a matched cohort of 72 adolescent and adult ALL patients treated with a modified version of Children's Cancer Group (CCG) 1900 protocol. RESULTS: The five years OS in the allo-HCT cohort was 63.1% compared to 80.2% in the pediatric-inspired chemotherapy arm (P = 0.03). The five years EFS in the allo-HCT arm was 58.8% compared to 61.6% in the pediatric-inspired chemotherapy arm (P = 0.07). The five years DFS in the allo-HCT arm was 58.8% as compared to 71.9% in the pediatric-inspired chemotherapy arm (P = 0.07). The relapse rate in the allo-HCT cohort was 30.58% compared to 21.68% in the pediatric-inspired chemotherapy arm (P = 0.16). The NRM in the allo-HCT cohort was 10.59 as compared to 6.45 in the pediatric-inspired chemotherapy arm (P = 0.3). CONCLUSION: For adolescent and adult patients with Ph-negative ALL, pediatric-inspired chemotherapy resulted in higher OS compared to allo-HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Recidiva Local de Neoplasia , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de Remissão , Estudos Retrospectivos
8.
EJHaem ; 2(2): 249-256, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-35845278

RESUMO

Secondary acute myeloid leukemia (sAML) includes AML as a complication of an antecedent hematological disorder or a therapy-related AML. Large registry-based data identified sAML as an independent poor-outcome type of AML post allogeneic hematopoietic cell transplantation (allo-HCT). In our study, we tried to define factors affecting outcomes of sAML post allo-HCT, and identify patients with sAML who may truly benefit from allo-HCT. We retrospectively analyzed the data of 64 patients aged (14-61 years) with sAML who received allo-HCT between September 2010 and February 2018 at our institute. Most of the patients were transplanted from matched related donors (MRD; 54, 84.4%). Our results showed that poor-risk cytogenetics were identified in 31 patients (48.4%), and their presence was an indicator of poor overall survival (OS) and disease-free survival (DFS; P-value = .009, and .004, respectively). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was significantly lower in sAML patients with poor-risk cytogenetics (P-value = .003) resulting in a high risk of death without cGVHD in this group of patients (P-value = .02). Besides, GVHD relapse-free survival (GRFS) analysis showed that most of our studied patients experienced either relapse or debilitating grade II-IV cGVHD in the first 2 years post allo-HCT. We conclude that sAML patients with poor-risk cytogenetics have a significantly lower DFS post allo-HCT with a high risk of death without active cGVHD.

9.
Leuk Res Rep ; 16: 100270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631407

RESUMO

BACKGROUND: Treating adolescents and young adults (AYA) patients with acute lymphoblastic leukemia (ALL) using pediatric-inspired protocols have shown improvement in outcomes. Most data available in the literature of such protocols is derived from well-controlled clinical trials. This report aims to provide a real-world experience from using a pediatric-inspired protocol in ALL-AYA population in larger number of patients treated at a national tertiary care referral center. METHODS: Newly diagnosed Philadelphia negative ALL-AYA patients ages between 14 and 55 years of age were treated on an institutional protocol (AYA-15 protocol) adopted from a modified version of Children's Cancer Group (CCG) 1900 protocol. At the time of this publication, a total of 79 patients were treated using the AYA-15 protocol between 2015 and 2020). Event-free survival (FFS), disease-free survival (DFS), and overall survival (OS) were analyzed using cumulative incidence and Kaplan-Meier methods. RESULTS: The median age at diagnosis was 18 years (14-51 years) with 63% male patients. Complete remission (CR) at day 28 of induction was achieved in 88.6% of which 73.4% were minimal residual disease (MRD) negative. At a median follow up of 5 years, EFS, DFS and OS were 57.5%, 69.2% and 75.8% respectively. Toxicities were within the expected range with infections and transaminitis being the most common adverse events. CONCLUSION: Our single-center experience real-world data in treating AYA-ALL patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18-55 years.

10.
Transplant Cell Ther ; 27(10): 851.e1-851.e6, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34126277

RESUMO

The recommended therapy for severe aplastic anemia (SAA) in younger patients with a matched sibling donor (MSD) is allogeneic hematopoietic cell transplantation (allo-HCT). A number of conditioning regimens and protocols have been used for these patients. Here we report a homogeneous cohort of SAA patients receiving a uniform transplantation protocol. This study is a retrospective analysis of 82 consecutive patients with SAA who underwent MSD allo-HCT at a single center. The median duration of follow-up for survivors was 100 months, the 10-year overall survival (OS) was 87.5%, and the 10-year event-free survival was 75.3%. The OS was 97.4% for "mobilized" bone marrow (BM) graft recipients and 78.9% for "nonmobilized" BM graft recipients (P = .01. The cumulative incidence of acute graft-versus-host disease (GVHD) was 25.6%, that of chronic GVHD was 27.16%, and that of graft failure was 16.2%. Recipient age ≥30 years and transplantation at >6 months after SAA diagnosis were associated with a increased risk of events. In the presence of a fully matched sibling donor, allo-HCT with a mobilized BM graft and fludarabine-cyclophosphamide conditioning is an efficacious and safe approach. Early transplantation is associated with a better outcome, emphasizing the importance of not delaying transplantation in these patients. Prospective trials are needed to determine the optimal regimen.


Assuntos
Anemia Aplástica , Adulto , Anemia Aplástica/terapia , Ciclofosfamida/uso terapêutico , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Irmãos , Vidarabina/análogos & derivados
11.
Hematol Oncol Stem Cell Ther ; 14(3): 169-178, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32888899

RESUMO

Saudi Arabia is the largest of the Arabian Gulf countries with a total population of 33.41 million as of 2017. This report summarizes the experience from four leading tertiary care hematopoietic stem cell transplantation (HSCT) centers in Saudi Arabia representing more than 90% of all HSCTs performed in the country. Between 1984 and 2016, a total of 6,184 HSCTs were performed. Of these, 3,586 HSCTs were performed in adults and 2,598 HSCTs were performed in pediatric patients. Malignancy was the main indication for transplantation (47%). While most transplants were performed from an identical sibling donor, HSCTs from cord blood, unrelated and, more recently, haploidentical donors have also been performed. Relative shortage of HSCT bed capacity is perceived to be a limiting factor in Saudi Arabia. Lately, more HSCT centers are emerging with rapid growth, which may significantly improve the access to HSCT in the country in the near future.


Assuntos
Transplante de Células-Tronco Hematopoéticas/história , Atenção Terciária à Saúde/história , Doadores de Tecidos , Condicionamento Pré-Transplante/história , História do Século XX , História do Século XXI , Humanos , Arábia Saudita
12.
Bone Marrow Transplant ; 55(1): 182-188, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31488877

RESUMO

Patients between 14 and 22 years old are underrepresented in both adult and pediatric studies. We analyzed the outcomes of 94 consecutive patients aged between 14 and 22 who underwent myeloablative matched related-donor transplant while in first or second complete remission. We studied the impact of disease type, remission status, ELN risk group, ABO mismatch, time from diagnosis to transplant, patient and donor age, conditioning type, stem cell source, and the year of transplant on transplant outcomes. The cumulative incidences of relapse, NRM, OS, and DFS at 5 years were 42%, 10%, 59%, and 48%, respectively. Absence of ABO mismatch and donor age > 20 were associated with better OS and DFS on univariate and multivariate analysis. The cumulative incidence of aGVHD and cGVHD were 18% and 44%, respectively. Donor age > 20 and peripheral blood stem cell source were significantly associated with higher incidence of cGVHD on univariate and multivariate analysis. Younger patient age was significantly associated with higher incidence of aGVHD. In this age group, the determinants of survival seem to be dependent on donor variables rather on the traditional disease and patient related variables. Relapse still a significant factor for transplant failure while NRM was low.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Criança , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/terapia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Condicionamento Pré-Transplante , Adulto Jovem
13.
Clin Lymphoma Myeloma Leuk ; 19(10): 670-677, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31377206

RESUMO

BACKGROUND: Treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients using traditional adult chemotherapy protocols give low overall survival (OS) rates. Data are growing regarding the use of pediatric-inspired chemotherapy protocols in AYA patients with improvement in OS. PATIENTS AND METHODS: To assess efficacy and tolerability of using a pediatric-inspired protocol in AYA patients, we initiated our local prospective trial using a modified version of the Children's Cancer Group 1900 protocol for newly diagnosed high-risk Philadelphia chromosome-negative ALL patients. RESULTS: A total of 40 patients were enrolled in the study (from 2015 to 2018). The median age was 18 years (range, 14-34 years). The complete remission rate after induction was 37 patients [93%] and after a median follow-up of 5 years, OS, disease-free survival (DFS), and event-free survival were 75%, 72%, and 60%, respectively. Use of this protocol was well tolerated with manageable toxicities. Pegylated asparaginase was given to all patients during the induction phase and was well tolerated. CONCLUSION: The use of a pediatric-inspired protocol for high-risk AYA ALL patients was effective and well tolerated with improvement in OS and DFS compared with historical data using adult protocols in such populations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Asparaginase/administração & dosagem , Asparaginase/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Neutropenia Febril/induzido quimicamente , Feminino , Humanos , Hiperbilirrubinemia/induzido quimicamente , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde/métodos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
14.
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
15.
Bone Marrow Transplant ; 53(7): 838-843, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29371685

RESUMO

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplant (allo-HCT) is challenging. Data on extramedullary relapse (EMR) after allo-HCT are limited. We analyzed 215 patients with AML who underwent allo-HCT in our institution between January 2005 and December 2015. We limited this retrospective review to patients who received a MA conditioning, were in complete remission (CR) at the time of transplant and who received a matched sibling transplant, all other patients were excluded to avoid heterogeneity. Seventy-seven (35.8%) patients experienced disease relapse, 45 had BMR, and 32 had EMR. The only variable that was statistically associated with EMR post allo-HCT was male sex (OR = 3.2 (1.2, 8.2), p-value = 0.01); there was a trend for association between transplant in >CR2 and EMR (OR = 0.38 (0.14, 1.06), p-value = 0.06). The median overall survival (OS) after relapse for all relapses was 10 months (95% CI 4.839-15.161). The median OS for BMR group was 8 months (95% CI 2.850-13.150) and 14 months for the EMR group (95% CI 5.776-22.224); however, this was not statistically significant, p-value = 0.4. Multivariate analysis revealed that gender, treatment modality, and time from allo-HCT to relapse (≥12 vs. <12 months) have significant association with the post-relapse death. Male gender was the only significant factor associated with EMR.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/cirurgia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adulto , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Recidiva , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
16.
Adv Hematol ; 2017: 4812637, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28321258

RESUMO

Multiple myeloma (MM) is a heterogeneous hematologic malignancy involving the proliferation of plasma cells derived by different genetic events contributing to the development, progression, and prognosis of this disease. Despite improvement in treatment strategies of MM over the last decade, the disease remains incurable. All efforts are currently focused on understanding the prognostic markers of the disease hoping to incorporate the new therapeutic modalities to convert the disease into curable one. We present this comprehensive review to summarize the current standard prognostic markers used in MM along with novel techniques that are still in development and highlight their implications in current clinical practice.

17.
Exp Clin Transplant ; 14(6): 660-664, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27447289

RESUMO

OBJECTIVES: Fanconi anemia is a congenital bone marrow failure syndrome that is associated with congenital anomalies and increased risk of cancer. Hematopoietic stem cell transplant is a potentially curative modality for bone marrow failure in Fanconi anemia patients. Here, we report our center's experience regarding adolescent and young adult patients with Fanconi anemia and hematopoietic stem cell transplant. MATERIALS AND METHODS: We conducted a retrospective patient record analyses of patients who presented at our center from 1988 to 2014. We included patients greater than 14 years old with confirmed Fanconi anemia based on positive chromosome breakage study and who underwent hematopoietic stem cell transplant at our institution. RESULTS: Our study group comprised 12 patients with Fanconi anemia who underwent hematopoietic stem cell transplant at our institution. The median age was 20 years (range, 14-31 y) with a female predominance of 83%. Low-dose cyclophosphamide (20-80 mg/kg)-based conditioning regimens were used with different combinations that included fludarabine, antithymocyte globulin, or total body irradiation. All patients had HLA-matched sibling grafts. In all patients, stem cell source was the bone marrow. All patients showed engraftment. Four patients (33%) developed acute graft-versus-host disease. Three patients (25%) died early before day 100 after hematopoietic stem cell transplant due to infectious complications, with 1 patient having steroid refractory acute graft-versus-host disease. Overall survival was 75% at a median follow-up of 43 months. All patients who survived are well and remained transfusion independent without evidence of secondary malignancy. CONCLUSIONS: Our findings support the feasibility of reduced intensity conditioning allogeneic hematopoietic stem cell transplant in older and more heavily pretreated patients with Fanconi anemia, especially for those who are engrafted.


Assuntos
Anemia de Fanconi/terapia , Transplante de Células-Tronco Hematopoéticas , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/mortalidade , Condicionamento Pré-Transplante , Adolescente , Adulto , Transplante de Medula Óssea , Anemia de Fanconi/mortalidade , Feminino , Reação Enxerto-Hospedeiro , Humanos , Masculino , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Adulto Jovem
18.
Biotechnol Res Int ; 2016: 8589270, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27006832

RESUMO

Background. We studied DNA chimerism in cell-free DNA (cfDNA) in patients treated with HSCT. Methods. Chimerism analysis was performed on CD3+ cells, polymorphonuclear (PMN) cells, and cfDNA using 16 small tandem repeat loci. The resulting labeled PCR-products were size-fractionated and quantified. Results. Analyzing samples from 191 patients treated with HSCT for nonneoplastic hematologic disorders demonstrated that the cfDNA chimerism is comparable to that seen in PMN cells. Analyzing leukemia patients (N = 126) showed that, of 84 patients with 100% donor DNA in PMN, 16 (19%) had evidence of clinical relapse and >10% recipient DNA in the plasma. Additional 16 patients of the 84 (19%) showed >10% recipient DNA in plasma, but without evidence of relapse. Eight patients had mixed chimerism in granulocytes, lymphocytes, and plasma, but three of these patients had >10% recipient DNA in plasma compared to PMN cells and these three patients had clinical evidence of relapse. The remaining 34 patients showed 100% donor DNA in both PMN and lymphocytes, but cfDNA showed various levels of chimerism. Of these patients 14 (41%) showed laboratory or clinical evidence of relapse and all had >10% recipient DNA in cfDNA. Conclusion. Monitoring patients after HSCT using cfDNA might be more reliable than cellular DNA in predicting early relapse.

19.
Int J Oncol ; 49(3): 913-33, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27573699

RESUMO

There is unmet need for prediction of treatment response for chronic myeloid leukemia (CML) patients. The present study aims to identify disease-specific/disease-associated protein biomarkers detectable in bone marrow and peripheral blood for objective prediction of individual's best treatment options and prognostic monitoring of CML patients. Bone marrow plasma (BMP) and peripheral blood plasma (PBP) samples from newly-diagnosed chronic-phase CML patients were subjected to expression-proteomics using quantitative two-dimensional gel electrophoresis (2-DE) and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of 2-DE protein fingerprints preceding therapy commencement accurately predicts 13 individuals that achieved major molecular response (MMR) at 6 months from 12 subjects without MMR (No-MMR). Results were independently validated using LC-MS/MS analysis of BMP and PBP from patients that have more than 24 months followed-up. One hundred and sixty-four and 138 proteins with significant differential expression profiles were identified from PBP and BMP, respectively and only 54 proteins overlap between the two datasets. The protein panels also discriminates accurately patients that stay on imatinib treatment from patients ultimately needing alternative treatment. Among the identified proteins are TYRO3, a member of TAM family of receptor tyrosine kinases (RTKs), the S100A8, and MYC and all of which have been implicated in CML. Our findings indicate analyses of a panel of protein signatures is capable of objective prediction of molecular response and therapy choice for CML patients at diagnosis as 'personalized-medicine-model'.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Proteômica/métodos , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/sangue , Medula Óssea/metabolismo , Calgranulina A/sangue , Calgranulina A/metabolismo , Cromatografia Líquida , Eletroforese em Gel Bidimensional , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-myc/sangue , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptores Proteína Tirosina Quinases/sangue , Receptores Proteína Tirosina Quinases/metabolismo , Espectrometria de Massas em Tandem , Resultado do Tratamento , Adulto Jovem
20.
Hematol Oncol Stem Cell Ther ; 8(2): 71-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25929729

RESUMO

Plasma cell leukemia (PCL) is a rare hematologic malignancy with very poor outcome. It is defined by the presence of >2 × 10(9)/L plasma cells or >20% plasmacytosis of the differential white cell count in the peripheral blood. Primary PCL is first diagnosed in the leukemic phase, while secondary PCL corresponds to the leukemic transformation of a previously diagnosed multiple myeloma (MM). The incidence of PCL ranges between 2-4% of patients with MM and 0.9% of patients with acute leukemia. In this case series, we describe the clinicopathologic, immunophenotypic, and cytogenetic findings of four patients diagnosed with PCL within a ten-year period (2002-2012) at King Faisal Specialist Hospital and Research Centre (General Organization), Riyadh, Saudi Arabia.


Assuntos
Leucemia Plasmocitária/patologia , Plasmócitos/patologia , Idoso , Análise Citogenética , Feminino , Testes Hematológicos , Humanos , Imunofenotipagem , Leucemia Plasmocitária/epidemiologia , Leucemia Plasmocitária/genética , Leucemia Plasmocitária/imunologia , Masculino , Pessoa de Meia-Idade , Plasmócitos/imunologia , Plasmócitos/metabolismo , Arábia Saudita/epidemiologia
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