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BACKGROUND: The impact of social determinants of health in allogeneic transplant recipients in low- and middle-income countries is poorly described. This observational study analyzes the impact of place of residence, referring institution, and transplant cost coverage (out-of-pocket vs government-funded vs private insurance) on outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) in two of Mexico's largest public and private institutions. AIM: To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in Mexico. METHODS: In this retrospective cohort study, we included adolescents and adults ≥ 16 years who received a matched sibling or haploidentical transplant from 2015-2022. Participants were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in Mexico. Three payment groups were compared: Out-of-pocket (OOP), private insurance, and a federal Universal healthcare program "Seguro Popular". Outcomes were compared between referred and institution-diagnosed patients, and between residents of Nuevo Leon and out-of-state. Primary outcomes included overall survival (OS), categorized by residence, referral, and payment source. Secondary outcomes encompassed early mortality, event-free-survival, graft-versus-host-relapse-free survival, and non-relapse-mortality (NRM). Statistical analyses employed appropriate tests, Kaplan-Meier method, and Cox proportional hazard regression modeling. Statistical software included SPSS and R with tidycmprsk library. RESULTS: Our primary outcome was overall survival. We included 287 patients, n = 164 who lived out of state (57.1%), and n = 129 referred from another institution (44.9%). The most frequent payment source was OOP (n = 139, 48.4%), followed by private insurance (n = 75, 26.1%) and universal coverage (n = 73, 25.4%). No differences in OS, event-free-survival, NRM, or graft-versus-host-relapse-free survival were observed for patients diagnosed locally vs in another institution, nor patients who lived in-state vs out-of-state. Patients who covered transplant costs through private insurance had the best outcomes with improved OS (median not reached) and 2-year cumulative incidence of NRM of 14% than patients who covered costs OOP (Median OS and 2-year NRM of 32%) or through a universal healthcare program active during the study period (OS and 2-year NRM of 19%) (P = 0.024 and P = 0.002, respectively). In a multivariate analysis, payment source and disease risk index were the only factors associated with overall survival. CONCLUSION: In this Latin-American multicenter study, the site of residence or referral for alloHSCT did not impact outcomes. However, access to healthcare coverage for alloHSCT was associated with improved OS and reduced NRM.
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BACKGROUND: Hematopoietic cell transplantation (HCT) is a promising treatment for hematological diseases, yet access barriers like cost and limited transplant centers persist. Telemedicine-based patient navigation (PN) has emerged as a solution. This study presents a cost-free PN telemedicine clinic (TC) in collaboration with the National Marrow Donor Program. AIM: to assess its feasibility and impac on HCT access determined by the cumulative incidence of transplantation. METHODS: In this single-center cohort study, patients of all ages and diagnoses referred for HCT participated. Two transplant physician-navigators established patient relationships via video calls, collecting medical history, offering HCT education and recommending pretransplant tests. The analysis involved descriptive statistics and intent-to-transplant survival assessment. RESULTS: One hundred and three patients were included of whom n = 78 were referred for allogeneic HCT (alloHCT), with a median age of 28 years. The median time from initial contact to the first consult was 5 days. The cumulative incidence of transplantation was 50% at 6 months and 61% at 12 months, with varying outcomes based on HCT type. Notably, 49 patients were not transplanted, primarily due to refractory disease, progression or relapse (57.1%). Autologous HCT candidates and physician referrals were correlated with higher transplant success compared to alloHCT candidates and patients who were not referred by a physician. CONCLUSION: Our pretransplant TC was feasible, facilitating access to HCT. Disease relapse posed a significant barrier. Enhancing timely physician referrals should be a focus for future efforts.
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Transplante de Células-Tronco Hematopoéticas , Navegação de Pacientes , Telemedicina , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adolescente , Criança , Adulto Jovem , Pré-Escolar , Acessibilidade aos Serviços de Saúde , Idoso , Estudos de Coortes , Lactente , Transplante Homólogo/métodosRESUMO
INTRODUCTION: High-dose melphalan (HD-Mel) has been successfully employed in autografting patients with multiple myeloma. An advantage of this regimen is that the total dose of Mel can be delivered in a single day, being particularly useful when non-frozen hematopoietic stem cells are employed in the autograft. MATERIAL AND METHODS: All consecutive patients with R/R lymphomas, both HL and NHL studied and treated at two different centers were prospectively included in a study of ASCT employing a single dose of HD-Mel (200â mg/m2). A group of R/R HL or NHL autografted employing BEAM-like preparative regimens was constructed matched by diagnosis and age. The primary endpoint of the study was overall survival (OS), the secondary endpoint was event-free survival (EFS). RESULTS: Twenty-five R/R HL/NHL patients were prospectively accrued in the study. There were 8 (32%) females, 13 (52%) patients had at least 1 adverse effect: 7 (28%) developed mucositis, 5 (20%) neutropenic fever, and 6 (24%) grade IV nausea. In the HD-Mel group, median overall survival (OS) was not achieved and OS at 36 months was 71%, the transplant-related mortality being 0%. In the control group, median OS was not achieved and the 36-month OS was 76%, results not statistically significant (p 0.5). The EFS was also similar in both groups (p 0.5). CONCLUSION: HD-Mel alone is non-inferior to a BEAM-like regimen as a preparative regimen for autografting patients with R/R HL and NHL. The regimen is adequate to graft persons with non-frozen stem cells.
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Transplante de Células-Tronco Hematopoéticas , Linfoma , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma/tratamento farmacológico , Melfalan/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante AutólogoRESUMO
Autologous hematopoietic stem cell transplantation (HSCT) has been recognized as treatment alternative for patients with severe, refractory autoimmune rheumatic diseases (ARDs). Usually, anti-thymocyte globulin (ATG)-containing conditioning regimens are employed; however, ATG is unavailable in some developing nations. We report our 15-year clinical experience autografting patients with ARDs with an ATG-free conditioning regimen and a brief assessment of patient-reported outcomes post-HSCT. All patients had active disease and were resistant to multiple lines of treatment. Event-free survival (EFS) was assessed using the Kaplan-Meier method. Eight patients underwent autologous HSCT. Diagnoses included juvenile idiopathic arthritis (n = 3), systemic lupus erythematosus (n = 2), systemic sclerosis (n = 2), and rheumatoid arthritis (n = 1). Median time from diagnosis to HSCT was 3 years (0.75-19). Hematological recovery was documented in all recipients, and 4 patients (50%) completed the procedure in a completely ambulatory setting. Five (62.5%) patients achieved complete response and 3 (37.5%) partial response. The median EFS was 7 months (95% CI, 4.97-9.02), and the 1-year EFS rate was 21.9% (95% CI, 18.25-25.76). Transplant-related mortality was 0%, and 1 recipient died 8 years post-HSCT due to chronic kidney disease. Six (75%) patients presented steroid dosage reduction post-HSCT, and 2 (25%) perceived improvement in functionality despite having relapsed. HSCT is a viable treatment alternative for selected patients with severe therapy-resistant ARDs, as an improvement in disease management and quality of life was documented. The need remains to elucidate the characteristics of the optimal HSCT candidate, as well as the adequate conditioning regimen when ATG is not available. Key Points ⢠Despite advances in the treatment of autoimmune rheumatic diseases, some patients remain refractory. In this context, autologous hematopoietic stem cell transplantation (HSCT) rises as a viable alternative. ⢠Of 8 HSCT recipients with autoimmune rheumatic diseases, 5 (62.5%) patients achieved complete response and 3 (37.5%) partial response, with a 1-year event-free survival of 21.9%. ⢠Transplant-related mortality was 0%, with 4 (50%) patients autografted in a completely outpatient setting. ⢠Even when relapse presented, patients reported an improvement in functionality and quality of life; also, a better response to DMARDs and a reduction in steroid dependency post-HSCT were documented.
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Artrite Reumatoide , Doenças Autoimunes , Transplante de Células-Tronco Hematopoéticas , Soro Antilinfocitário , Artrite Reumatoide/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , América Latina , Qualidade de Vida , Transplante AutólogoRESUMO
The aim of this study was to assess the feasibility of hematopoietic cell transplantation (HCT) data collection using an electronic platform at Mexican centers. Four public centers performing HCT in adults were included. A cloud-based electronic platform in Spanish was developed to allow real-time registration of demographic, clinical, and outcomes variables. Data were obtained from paper and electronic medical records and institutional databases. Data managers were hired to perform the collection. Data from January 2015 to December 2018 were retro and prospectively collected during a 10-month period. From 2015 to 2018, 473 HCT were performed. Most were autologous (55%). Patients undergoing autologous HCT had the highest median age (49 years) compared with patients undergoing allogeneic (34 years) or haploidentical HCT (29 years). The most common underlying disease for autologous HCT was multiple myeloma. Acute leukemias were the most common diagnoses among allogeneic and haploidentical HCT recipients. Two-year nonrelapse mortality was 2.5%, 18%, and 18% for autologous, allogeneic, and haploidentical HCT, respectively. We determined it was feasible to start a multicenter collaborative study in Mexico as it was very well received by the physicians and it can lead to the creation of a Mexican HCT Registry in the near future.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Adulto , Humanos , México , Pessoa de Meia-Idade , Sistema de Registros , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
BACKGROUND: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. OBJECTIVE: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. METHODS: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. RESULTS: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. CONCLUSION: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.
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Cadeias beta de HLA-DP , Doenças Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Haploidêntico , Adolescente , Adulto , Criança , Pré-Escolar , Seleção do Doador , Feminino , Doenças Hematológicas/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
ABSTRACT Background: The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative effect on survival has been suggested. Objective: The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting. Methods: Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS. Results: Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified. Conclusion: HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.
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Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Transplante de Células-Tronco Hematopoéticas/métodos , Cadeias beta de HLA-DP , Transplante Haploidêntico , Doenças Hematológicas/cirurgia , Taxa de Sobrevida , Estudos Retrospectivos , Resultado do Tratamento , Seleção de Pacientes , Seleção do Doador , Doenças Hematológicas/mortalidadeRESUMO
RESUMEN Objetivo El dengue es una enfermedad viral generalmente autolimitada, que en México se considera un problema de salud pública. Puede acompañarse de alteraciones de laboratorio como neutropenia, linfopenia y trombocitopenia. El objetivo del estudio fue evaluar la incidencia de alteraciones hematológicas en pacientes con dengue. Métodos Se incluyeron retrospectivamente 64 pacientes, 14 embarazadas, con diagnóstico de dengue en los Hospitales Universitario de Monterrey y Civil Nuevo de Guadalajara, de enero de 2014 a diciembre de 2017. Resultados El dato clínico más común en el grupo general fue cefalea y dolor retroocular en 53 pacientes (83%), seguido de la fiebre, que se presentó en 12 pacientes embarazadas (86%). La mediana de cuenta plaquetaria en el grupo general fue de 51.4x103/pl, además, se encontró trombocitopenia en el 88% de los pacientes, mientras que en las pacientes embarazadas fue de 141.1 x103/pl, con trombocitopenia en 57% de ellas (p=0.002). La recuperación plaquetaria ocurrió en 7 días en el grupo general y 4.5 días en las pacientes embarazadas. Conclusiones Contrario a lo reportado en la literatura, las pacientes embarazadas presentaron una menor incidencia de trombocitopenia y una mayor cuenta plaquetaria, al momento del diagnóstico sin impacto en mortalidad materna ni en el curso del embarazo.(AU)
ABSTRACT Objective Dengue is a generally self-limited viral disease, considered a public health problem in Mexico. It can be accompanied by laboratory alterations such as neutropenia, lymphopenia and thrombocytopenia. The objective of the study was to evaluate the incidence of hematological alterations in patients with dengue. Methods We retrospectively included 64 patients, including 14 pregnant women, with a diagnosis of dengue at the Hospital Universitario de Monterrey and Civil Nuevo de Guadalajara from January 2014 to December 2017. Results The most common clinical symptom in the general group was headache and retro-ocular pain in 53 patients (83%), while in pregnant patients it was fever in 12 patients (86%). The median platelet count in the general group was 51.4x103/ μ!, with thrombocytopenia in 88% of patients, while in pregnant patients it was 141.1 x103/ with thrombocytopenia in 57% of patients (p=0.002). Platelet recovery was achieved in 7 days in the general group and 4.5 days in pregnant patients. Conclusions Contrary to that reported in the literature, pregnant patients had a lower incidence of thrombocytopenia and a higher platelet count at time of diagnosis without impact on maternal mortality or in the course of pregnancy.(AU)
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Humanos , Feminino , Gravidez , Complicações Infecciosas na Gravidez , Trombocitopenia/epidemiologia , Dengue/epidemiologia , Estudos Retrospectivos , México/epidemiologiaRESUMO
INTRODUCTION: The use of filgrastim biosimilars for healthy adult and pediatric donor mobilization in hematopoietic stem cell transplantation has been met with increased safety and efficacy concerns in contrast to generic small molecule drugs. In Mexico, several filgrastim-intended copies (FIC) have been available and marketed since 2001, while no clinical comparability studies to evaluate their use in this setting have been published and thus are not considered to be true biosimilars. In this study, we report our experience using three different FIC products currently available (Filatil, Dextrifyl, and Biofilgran). METHODS: We retrospectively evaluated 118 related donors of all ages who received any brand 5 µg/kg subcutaneously twice daily for 4 days and were harvested in a single apheresis system on day 5. RESULTS: Donors had a median age of 38 years (range, 1-69). A successful harvest defined as ≥2 × 106 CD34+ cells/kg of recipient weight was achieved in 95.8% of cases, with a median CD34+ cell dose of 9.4 × 106 /kg (range 1-42.8). A single apheresis session was performed in 89.8% of cases. No significant difference in cell yield between each brand was observed. All pediatric donors had a successful harvest with similar results to adult donors. No immediate severe adverse effects were documented in any case. CONCLUSIONS: In conclusion, three FICs available in Mexico were efficacious and without immediate severe adverse effects, resulting in significant cost savings. Evaluation of immunogenicity and establishment of a pharmacovigilance program with the use of FICs is warranted.
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Substituição de Medicamentos/normas , Filgrastim/normas , Mobilização de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Antígenos CD34/análise , Criança , Pré-Escolar , Filgrastim/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/economia , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Lactente , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Dengue is a generally self-limited viral disease, considered a public health problem in Mexico. It can be accompanied by laboratory alterations such as neutropenia, lymphopenia and thrombocytopenia. The objective of the study was to evaluate the incidence of hematological alterations in patients with dengue. METHODS: We retrospectively included 64 patients, including 14 pregnant women, with a diagnosis of dengue at the Hospital Universitario de Monterrey and Civil Nuevo de Guadalajara from January 2014 to December 2017. RESULTS: The most common clinical symptom in the general group was headache and retro-ocular pain in 53 patients (83%), while in pregnant patients it was fever in 12 patients (86%). The median platelet count in the general group was 51.4x103/ µ!, with thrombocytopenia in 88% of patients, while in pregnant patients it was 141.1 x103/ with thrombocytopenia in 57% of patients (p=0.002). Platelet recovery was achieved in 7 days in the general group and 4.5 days in pregnant patients. CONCLUSIONS: Contrary to that reported in the literature, pregnant patients had a lower incidence of thrombocytopenia and a higher platelet count at time of diagnosis without impact on maternal mortality or in the course of pregnancy.
OBJETIVO: El dengue es una enfermedad viral generalmente autolimitada, que en México se considera un problema de salud pública. Puede acompañarse de alteraciones de laboratorio como neutropenia, linfopenia y trombocitopenia. El objetivo del estudio fue evaluar la incidencia de alteraciones hematológicas en pacientes con dengue. MÉTODOS: Se incluyeron retrospectivamente 64 pacientes, 14 embarazadas, con diagnóstico de dengue en los Hospitales Universitario de Monterrey y Civil Nuevo de Guadalajara, de enero de 2014 a diciembre de 2017. RESULTADOS: El dato clínico más común en el grupo general fue cefalea y dolor retroocular en 53 pacientes (83%), seguido de la fiebre, que se presentó en 12 pacientes embarazadas (86%). La mediana de cuenta plaquetaria en el grupo general fue de 51.4x103/pl, además, se encontró trombocitopenia en el 88% de los pacientes, mientras que en las pacientes embarazadas fue de 141.1 x103/pl, con trombocitopenia en 57% de ellas (p=0.002). La recuperación plaquetaria ocurrió en 7 días en el grupo general y 4.5 días en las pacientes embarazadas. CONCLUSIONES: Contrario a lo reportado en la literatura, las pacientes embarazadas presentaron una menor incidencia de trombocitopenia y una mayor cuenta plaquetaria, al momento del diagnóstico sin impacto en mortalidad materna ni en el curso del embarazo.
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Dengue , Trombocitopenia , Humanos , Feminino , Gravidez , Dengue/complicações , Dengue/epidemiologia , Estudos Retrospectivos , Incidência , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Contagem de PlaquetasAssuntos
Benzoatos/administração & dosagem , Dexametasona/administração & dosagem , Hidrazinas/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Pirazóis/administração & dosagem , Rituximab/administração & dosagem , Adolescente , Adulto , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/diagnósticoRESUMO
We studied rates of granulocyte and platelets recovery in 359 consecutive subjects receiving blood cell infusions in the context of autotransplants for plasma cell myeloma (N = 216) and lymphomas (N = 143). Blood cells were mobilised with filgrastim given for 4-5 days and collected after a median of 2 (range, 1-2) apheresis. Apheresis products were stored at 4° C for a median of 3 days (range, 2-6 days). Most subjects received carmustine, etoposide, cytarabine and melphalan (BEAM), cyclophosphamide, carmustine and etoposide (CBV) or high-dose melphalan. Filgrastim was given post transplant to 319 subjects. Median numbers of mononuclear cells collected was 31 × 10E + 6/kg (interquartile range (IQR) 37 × 10E + 6 cells/kg). Median numbers of CD34-positive cells collected was 3.6 × 10E + 6/kg (IQR 3.8 × 10E + 6/Kg). Median viability after collection was 90% (IQR 7%) after storage, 88% (IQR 12%). A total of 255 of 256 evaluable subjects recovered bone marrow function and there was no late bone marrow failure. Median interval to neutrophils >0.5 × E + 9/L was 13 days (range, 9-39 days) and to platelets >20 × 10E + 9/L, 16 days (range, 7-83 days). These rates and ranges seem comparable to those reported after autotransplants of frozen blood cells. There was no correlation between numbers of storage days at 4 °C and viability afte storage (r = -0.018, p = 0.14)) nor rates of recovery of neutrophils (r = -0.054, p = 0.52) or platelets (r = 0.116, p = 0.14). Blood cells collected for autotransplant can be stored at 4 °C for 6 d. This method is simple, inexpensive and widely applicable.
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Autoenxertos , Congelamento , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Remoção de Componentes Sanguíneos/métodos , Preservação de Sangue/métodos , Sobrevivência Celular , Criança , Pré-Escolar , Sobrevivência de Enxerto , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: This article reviews clinical experiences in the treatment of chronic myeloid leukemia (CML) in an environment of limited resources. METHODS: We reviewed recent publications on Pub med and abstracts from mayor congresses relevant to the disease. RESULTS: CML is a hematological neoplasm observed more frequently in adults, regardless of their socioeconomic status. Until recently, available treatments improved patients' quality of life but did not modify survival. It was not until interferon appeared that patients received a drug that reduced and even eliminated Philadelphia chromosome-positive (Ph+) cells. DISCUSSION: With the start of the new millennium, the International Randomized Study of Interferon-α plus cytarabine versus STI571 (IRIS) trial demonstrated a dramatic improvement in survival by comparing imatinib versus interferon alpha plus cytarabine. The Food and Drug Administration (FDA) approved imatinib as first-line treatment for newly diagnosed CML in 2001 due to its outstanding effectiveness. Years later, three second-generation (dasatinib, nilotinib, bosutinib) and one third-generation (ponatinib) tyrosine-kinase inhibitors (TKIs) were developed and approved. These highly effective treatment options, however, are not affordable for many low-income patients. Additionally, the use of drugs that effectively treat but do not cure the disease has resulted in an important economic impact for patients and health care systems worldwide, especially those in developing countries. Imatinib is the least expensive and a very effective TKI in many low-income countries. Early allogeneic stem cell transplantation must be considered in the management of selected patients before CML transformation.
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Antineoplásicos/uso terapêutico , Recursos em Saúde/normas , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Antineoplásicos/economia , Recursos em Saúde/economia , Humanos , Mesilato de Imatinib/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologiaRESUMO
Fasting serum prolactin (PRL) levels in response to metoclopramide (MCP) and lymphocyte cytokine profiles was studied in patients given allografts and their donors. Thirty normoprolactinemic volunteers (12-59 years) were studied: group 1, 10 healthy men; group 2, 8 males and 2 females with various hematologic diseases; and group 3, 3 males and 7 females HLA-identical sibling donors: PRL and cytokines were measured. Four surviving recipients developed acute graft-versus-host disease (GVHD) (+), and six did not. Before transplant Fasting PRL concentrations were higher in 'future' GVHD(+) recipients than in their donors (P < 0.001). The opposite was seen in response to MCP (P = 0.01). Donors had a predominant T-helper type 1 (Th1) cytokine profile compared with recipients (P ≤ 0.02), and GVHD(+) recipients had a greater tumor necrosis factor (TNF) value than GVHD(-) (P = 0.05). After transplant On days +30 and +100, a mild sustained rise in fasting PRL levels occurred only in GVHD(+) recipients (P ≤ 0.05) simultaneously with a transient rise in Th1 cytokines. GVHD(-) recipients had no changes. Donors with a Th1 cytokine profile might be more prone to induce GVHD in their recipients, and a mild sustained rise in PRL concentrations after transplantation in recipients GVHD(+) might participate in the amelioration of the severity of GVHD.
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Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Hiperprolactinemia/imunologia , Prolactina/imunologia , Doença Aguda , Adolescente , Adulto , Criança , Citocinas/imunologia , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Antígenos HLA/imunologia , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/mortalidade , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Índice de Gravidade de Doença , Irmãos , Taxa de Sobrevida , Equilíbrio Th1-Th2 , Doadores de Tecidos , Transplante HomólogoRESUMO
Immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) plus cyclosporine A (CsA) is the standard treatment for aplastic anemia (AA) patients not eligible for allogeneic hematopoietic stem cell transplantation (HSCT). In the absence of ATG + CsA, androgens continue to be a treatment option. We documented the clinical evolution of AA patients treated with danazol instead of ATG + CsA. AA patients lacking both, human leukocyte antigen-matched donor and access to IST, were treated with danazol and modern support therapy and compared with those receiving a HSCT. Overall survival (OS), response rates, and death risk odds were calculated. Fifty AA patients were studied. Thirteen received a HSCT and 37 danazol and support therapy. Median daily dose of danazol was 400 mg (300 to 600 mg), administered during a median of 12 months. Five-year OS was higher for patients receiving HSCT (92%) compared to the danazol group (41%) (P = 0.001). Overall response rate was 46% (17/37) in the danazol-treated group and the median time to initial response was 3 months (1-27). Tendency to achieve remission was similar among severity groups (P = 0.094). The only adverse side effect recorded on the danazol group was an episode of gastrointestinal bleeding. No patient treated with danazol suffered clonal evolution of his/her disease. Although ATG plus CsA is the therapy of choice for AA patients without a donor when neither HSCT nor IST is available, danazol remains an acceptable therapeutic option for AA patients.
Assuntos
Androgênios/uso terapêutico , Anemia Aplástica/tratamento farmacológico , Danazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Androgênios/efeitos adversos , Anemia Aplástica/terapia , Criança , Danazol/efeitos adversos , Países em Desenvolvimento , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Longitudinais , Masculino , México , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Since 1999, in Mexico we have been using a regimen to conduct allografts that involves non-myeloablative conditioning and peripheral blood stem cells (PBSC) and have introduced some changes with the main goal of decreasing the cost of the procedure. MATERIALS AND METHODS: We analysed the salient apheresis features of a group of 175 allogeneic peripheral blood stem cell transplants conducted in two institutions in a 7-year period. The grafts were conducted using the "Mexican" non-myelo ablative conditioning regimen employing oral busulphan, i.v. cyclophosphamide and i.v. fludarabine. In all instances, the apheresis machine employed was the Baxter CS3000 Plus and donors were mobilised with filgrastim. The apheresis procedures were performed on days 0, +1 and +2, the end-point of collection being 5,000 mL of blood/m2 in each procedure. Three apheresis sessions were planned but the number was adjusted according to the cell yield. RESULTS: The final number of allografted CD34 cells ranged between 0.5 and 25.4 x 10(6)/Kg of the recipient's body weight (median, 5.2 x 10(6)/Kg). One to three apheresis procedures were needed to obtain a product containing more than 0.5 x 10(6) CD34 cells/Kg of the recipient, the median being two procedures; in 72 cases (41%) a single apheresis procedure was sufficient to obtain the target number of CD34 cells. The volumes of apheresis ranged between 50 and 600 mL (median, 400 mL). CONCLUSIONS: Since the median cost of each apheresis procedure is 900 USD, the fact that two apheresis procedures was spared in 72 cases and one apheresis was spared in another 65 cases, led to a total saving of approximately 188,100 USD. It can be concluded that, in many cases, allogeneic transplants can be completed with a single apheresis session and that there are considerable financial benefits from this practice.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Remoção de Componentes Sanguíneos/métodos , Doadores de Sangue , Ablação por Cateter , Neoplasias Hematológicas/terapia , Anemia Aplástica/terapia , Remoção de Componentes Sanguíneos/economia , Bussulfano/administração & dosagem , Análise Custo-Benefício , Ciclofosfamida/administração & dosagem , Filgrastim , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Hematológicas/economia , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , México , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Proteínas Recombinantes , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo/métodos , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
We studied the effectiveness of a fludarabine/cyclophosphamide-based conditioning regimen without anti-thymocyte globulin in 23 aplastic anemia patients who had no response to previous conventional pharmacologic treatment. Patients received oral busulphan 4 mg/kg/day/2 days, IV cyclophosphamide 350 mg/m(2)/day/3 days, and fludarabine 30 mg/m(2)/day/3 days. For GVHD prophylaxis, patients received MTX 5 mg/m(2) days +1, +3, +6, and +11 and oral cyclosporin A (CyA) 5 mg/kg/day, starting on day -1. Peripheral blood stem cell products were used with a median dose of 5.5 x 10(6) CD34(+)/kg. The patients were followed for an average of 25 months. By a median of day +11, an ANC > 0.5 x 10(9)/L was reached; and by day +12, the platelet count had reached >20,000 x 10(9)/L. Acute grade I-II GVHD occurred in 4 patients, whereas limited chronic GVHD presented in 6 cases. Twenty-one patients (91.3%) achieved engraftment. Two patients failed to engraft, and 4 developed late rejection; 2 of these individuals died, 2 have survived with high transfusion requirements, whereas 2 received a second peripheral blood stem cell infusion and achieved sustained engraftment. Currently 21 (91%) of the 23 patients are alive, whereas 19 of 21 (90%) remain in complete remission. The average cost was about USD 15,000 for this kind of reduced-intensity allotransplant. Reduced-intensity stem cell transplantation represents an affordable alternative to traditional more cytotoxic conditioning for severe aplastic anemia (SAA) patients. Long-term effects however, remain to be evaluated.
Assuntos
Anemia Aplástica/terapia , Bussulfano/administração & dosagem , Ciclofosfamida/administração & dosagem , Agonistas Mieloablativos/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Adolescente , Adulto , Idoso , Anemia Aplástica/complicações , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Ciclosporina/administração & dosagem , Intervalo Livre de Doença , Feminino , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , México , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Transplante Homólogo , Vidarabina/administração & dosagemRESUMO
The feasibility of applying allogeneic cell -mediated therapy in conjunction with allogeneic hematopoietic cell transplantation following reduced -intensity conditioning, with minimal toxicity and no serious transplant-related complications, makes it possible to perform such procedures on an outpatient basis as well to offer a valid option for cure to elderly individuals and patients with less than optimal performance status. Based on available experience, clinical application of this innovative therapy may open new horizons for the treatment of patients with leukemia, lymphoma, myeloma and other diseases. Many patients can now benefit from the advantages of immunotherapy mediated by alloreactive donor lymphocytes, while minimizing transplant-related toxicity and mortality. This kind of transplant is making real progress in the world of transplantation.
El trasplante alogénico no mieloablativo basa su efecto en la capacidad de los linfocitos del donador de erradicar a la enfermedad residual del paciente. El empleo de dosis reducidas de intensidad de radioterapia y/o quimioterapia permite su empleo en pacientes de edad avanzada y aún con comorbilidad. La poca toxicidad del procedimiento evita frecuentemente la hospitalización del paciente, se asocia a menor frecuencia de infecciones y de transfusiones, por ello el costo es sensiblemente menor e ideal para países pobres. Se ha utilizado con éxito desde hace ocho años y en nuestro país su aplicación es cada vez más frecuente. La utilidad principal se ha observado en leucemias crónicas y linfomas indolentes. En leucemia aguda mieloblástica en primera remisión también es útil, siendo menos efectivo en la leucemia aguda linfoblástica y los linfomas no-Hodgkin agresivos. También puede ser utilizado en niños y en pacientes con enfermedades benignas. El trasplante no-mieloablativo es una realidad en el área de los trasplantes.
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante/métodos , Ensaios Clínicos como Assunto , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Previsões , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/cirurgia , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , México , Quimeras de Transplante , Transplante Homólogo , Resultado do Tratamento , Condicionamento Pré-Transplante/mortalidade , Condicionamento Pré-Transplante/estatística & dados numéricosRESUMO
The feasibility of applying allogeneic cell -mediated therapy in conjunction with allogeneic hematopoietic cell transplantation following reduced -intensity conditioning, with minimal toxicity and no serious transplant-related complications, makes it possible to perform such procedures on an outpatient basis as well to offer a valid option for cure to elderly individuals and patients with less than optimal performance status. Based on available experience, clinical application of this innovative therapy may open new horizons for the treatment of patients with leukemia, lymphoma, myeloma and other diseases. Many patients can now benefit from the advantages of immunotherapy mediated by alloreactive donor lymphocytes, while minimizing transplant-related toxicity and mortality. This kind of transplant is making real progress in the world of transplantation.