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2.
Exp Clin Transplant ; 22(4): 270-276, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38742317

RESUMEN

OBJECTIVES: Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as infection and malignancy. Furthermore, the effects of the routine use of immunosuppressants in low-risk kidney transplant recipients are still not clear. In this study, we assessed the first-year safety and efficacy of induction treatment. MATERIALS AND METHODS: We examined first living donor kidney transplant patients who were on tacrolimus based immunosuppression therapy. We formed 3 groups according to the induction status: antithymocyte globulin induction, basiliximab induction, and no induction. We collected outcome data on delayed graft function, graft loss, creatinine levels, estimated glomerular filtration rates, acute rejection episodes, hospitalization episodes, and infection episodes, including cytomegalovirus infection and bacterial infections. RESULTS: We examined a total of 126 patients (age 35 ± 12 years; 65% male). Of them, 25 received antithymocyte globulin, 52 received basiliximab, and 49 did notreceive any induction treatment. We did not observe any statistically significant difference among the 3 groups in terms of acute rejection episodes, delayed graft function, and first-year graft loss. The estimated glomerular filtration rates were similar among the groups. Overall bacterial infectious complications and cytomegalovirus infection showed similar prevalence among all groups. Hospitalization was less common in the induction-free group. CONCLUSIONS: In low-risk patients, induction-free regimens could be associated with a better safety profile without compromising graft survival. Therefore, induction treatment may be disregarded in first living donor transplant patients who receive tacrolimusbased triple immunosuppression treatment.


Asunto(s)
Suero Antilinfocítico , Basiliximab , Inmunosupresores , Trasplante de Riñón , Donadores Vivos , Tacrolimus , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Suero Antilinfocítico/efectos adversos , Suero Antilinfocítico/uso terapéutico , Basiliximab/efectos adversos , Basiliximab/uso terapéutico , Inhibidores de la Calcineurina/efectos adversos , Inhibidores de la Calcineurina/administración & dosificación , Funcionamiento Retardado del Injerto/inmunología , Quimioterapia Combinada , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/efectos adversos , Tacrolimus/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento
3.
Am J Transplant ; 24(8): 1486-1494, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38447887

RESUMEN

Posttransplant lymphoproliferative disorder (PTLD) poses a significant concern in Epstein-Barr virus (EBV)-negative patients transplanted from EBV-positive donors (EBV R-/D+). Previous studies investigating the association between different induction agents and PTLD in these patients have yielded conflicting results. Using the Organ Procurement and Transplant Network database, we identified EBV R-/D+ patients >18 years of age who underwent kidney-alone transplants between 2016 and 2022 and compared the risk of PTLD with rabbit antithymocyte globulin (ATG), basiliximab, and alemtuzumab inductions. Among the 6620 patients included, 64.0% received ATG, 23.4% received basiliximab, and 12.6% received alemtuzumab. The overall incidence of PTLD was 2.5% over a median follow-up period of 2.9 years. Multivariable analysis demonstrated that the risk of PTLD was significantly higher with ATG and alemtuzumab compared with basiliximab (adjusted subdistribution hazard ratio [aSHR] = 1.98, 95% confidence interval [CI] 1.29-3.04, P = .002 for ATG and aSHR = 1.80, 95% CI 1.04-3.11, P = .04 for alemtuzumab). However, PTLD risk was comparable between ATG and alemtuzumab inductions (aSHR = 1.13, 95% CI 0.72-1.77, P = .61). Therefore, the risk of PTLD must be taken into consideration when selecting the most appropriate induction therapy for this patient population.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Rechazo de Injerto , Supervivencia de Injerto , Herpesvirus Humano 4 , Inmunosupresores , Trasplante de Riñón , Trastornos Linfoproliferativos , Complicaciones Posoperatorias , Donantes de Tejidos , Humanos , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/etiología , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/virología , Persona de Mediana Edad , Adulto , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Rechazo de Injerto/etiología , Suero Antilinfocítico/efectos adversos , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Receptores de Trasplantes , Incidencia , Quimioterapia de Inducción/efectos adversos , Basiliximab , Alemtuzumab/efectos adversos , Pruebas de Función Renal
4.
J Cancer Res Clin Oncol ; 150(3): 152, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38517548

RESUMEN

INTRODUCTION: Long-term survivors have an increased risk of developing secondary solid malignancies (SSMs) after allogeneic-hematopoietic stem cell transplantation (allo-HSCT) with graft-versus-host disease (GVHD) potentially modulating these risks. METHODS: This retrospective study analyzed the cumulative incidences of SSMs after chemotherapy-based conditioning for allo-HSCT patients with acute myeloid leukemia (n = 266) transplanted at the University Hospital Regensburg between 1999 and 2016. RESULTS: The median follow-up was 11.4 years (Interquartile range, 9.0-14.9). The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 44.4% [95% CI (38.3, 50.2)], while the 5-year cumulative incidence of chronic GVHD (cGVHD, requiring systemic immunosuppression) was 36.9% [95% CI (31.1, 42.6)]. The cumulative incidences of secondary squamous cell carcinomas (SCCs) at 10 and 15 years were 4.2% [95% CI (2.2, 7.2)] and 8.1% [95% CI (4.6, 12.8)], while the cumulative incidences of non-SCCs at 10 and 15 years were 5.4% [95% CI (3.1, 8.7)] and 6.9% [95% CI (4.0, 10.8)]. Antithymocyte globulin (ATG) was associated with reduced incidences of SCCs but not of non-SCCs. Patients with grade II-IV aGVHD had increased rates of SCCs after adjusting with patient age and ATG, while patients with cGVHD showed only a trend for increased rates of SCCs. CONCLUSION: The data indicate that aGVHD and cGVHD affect the rates of secondary SCCs. While the use of ATG is associated with lower incidences of SCCs via reduction of GVHD, there was no association of ATG with non-SCCs.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Lesiones Precancerosas , Humanos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/terapia , Suero Antilinfocítico/efectos adversos , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Acondicionamiento Pretrasplante/efectos adversos
5.
Eur J Haematol ; 112(3): 424-432, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37929654

RESUMEN

Aplastic anemia (AA) is a rare bone marrow failure disorder that is treated with either allogeneic stem cell transplant or immunosuppressive therapy (IST) consisting of antithymocyte globulin (ATG), cyclosporine (CSA), and eltrombopag. While outcomes are favorable in younger patients, older patients (>60) have significantly worse long-term survival. The dose of ATG is often reduced in older patients and those with multiple comorbidities given concerns for tolerability. The efficacy and safety of dose-attenuated IST in this population is largely undescribed. We performed a retrospective review of patients with AA treated with IST. Our analysis was confounded by changes in practice patterns and the introduction of eltrombopag. We identified 53 patients >60 years old, of which, 20 received dose-attenuated IST, with no statistically significant difference in overall survival between full and attenuated dose cohorts. Overall response rates in both cohorts were similar at 6 months at 71% and 68%. There were more documented infectious complications in the full dose cohort (13 vs. 3). This supports the consideration of dose-attenuated IST in older patients with concerns about tolerance of IST. Lastly, our data confirmed favorable outcomes of younger patients receiving IST, especially in combination with eltrombopag.


Asunto(s)
Anemia Aplásica , Benzoatos , Hidrazinas , Inmunosupresores , Pirazoles , Humanos , Anciano , Persona de Mediana Edad , Inmunosupresores/efectos adversos , Anemia Aplásica/diagnóstico , Anemia Aplásica/tratamiento farmacológico , Resultado del Tratamiento , Ciclosporina/efectos adversos , Terapia de Inmunosupresión , Suero Antilinfocítico/efectos adversos
6.
Transplant Proc ; 55(9): 2035-2040, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37778934

RESUMEN

BACKGROUND: Cytomegalovirus (CMV) infection remains one of the most common viral pathogens affecting solid organ transplants (SOT). In 10 years of following the outcome of transplants, we noticed an increased incidence of CMV infection, along with increased use of rabbit anti-thymocyte globulin (rATG). The study aims to assess the incidence of active CMV infection and disease, response to treatment, and recurrence in a cohort of SOT. Furthermore, we look for correlating the CMV incidence with the type of induction therapy: r-ATG or interleukin 2 receptor-blocking antibody (basiliximab). METHODS: This was a single-center, retrospective 10-year study in patients submitted to kidney, kidney-liver, and kidney-pancreas transplants who used a preemptive therapy protocol for CMV. RESULTS: Among the 476 enrolled transplant recipients, 306 (64.2 %) had at least one episode of CMV infection (replication), and 71/306 patients (23.2 %) presented CMV-related disease. The most frequent clinical conditions associated with CMV disease were gastrointestinal. Among the 476 transplant patients, 333 received immunosuppressive induction with rATG (69.9 %); 140 (29.4 %) received induction with interleukin 2 receptor-blocking antibody (basiliximab). The initial maintenance immunosuppressive therapy in the patients who presented CMV infection was primarily performed with prednisone, tacrolimus, and sodium mycophenolate (91.7 %). The induction with rATG increased from 35.2%-94.6% in 10 years. The incidence of CMV infection was 20.7 % in the first year of observation and gradually increased to 87.3 % in the last year. CONCLUSIONS: The data suggest that the increase in the use of rATG in recent years could be responsible for the very expressive increase in the incidence of CMV infection/disease.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Riñón , Trasplante de Órganos , Humanos , Suero Antilinfocítico/efectos adversos , Citomegalovirus , Basiliximab/uso terapéutico , Estudios Retrospectivos , Quimioterapia de Inducción , Trasplante de Riñón/efectos adversos , Rechazo de Injerto , Inmunosupresores/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/tratamiento farmacológico , Trasplante de Órganos/efectos adversos , Receptores de Interleucina-2
7.
Int J Clin Pharmacol Ther ; 61(12): 551-560, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37877292

RESUMEN

OBJECTIVE: Several studies have reported that porcine antilymphocyte globulin (pALG) has a significant effect on aplastic anemia (AA), but their conclusions are inconsistent. To objectively evaluate its efficacy and safety, a meta-analysis was conducted. MATERIALS AND METHODS: We systematically searched the relevant literature on pALG vs. rabbit antithymocyte globulin (rATG) as the first-line treatment in AA patients until August 31, 2022, in electronic databases: PubMed, Cochrane Library, Web of Science, etc. Two researchers independently extracted data and evaluated the quality of the study. Stata 14.0 was used for statistical analysis. RESULTS: 50 studies were included in the analysis. The overall responses at 3, 6, and 12 months between the pALG group and rATG group were equivalent. We analyzed early mortality, total mortality, relapse rates, and 5-year survival after the administration of pALG or rATG, and there was no significant difference between the pALG and rATG groups. In our study, the incidence of infection in the pALG group was better than that in the rATG group, OR = 0.63, 95% CI (0.44 - 0.88), p = 0.008, which showed a statistically significant difference. CONCLUSION: The efficacy of pALG in AA patients is equivalent to that of rATG. rATG was associated with a significantly higher incidence rate of infection than pALG.


Asunto(s)
Anemia Aplásica , Suero Antilinfocítico , Humanos , Animales , Porcinos , Suero Antilinfocítico/efectos adversos , Anemia Aplásica/diagnóstico , Anemia Aplásica/tratamiento farmacológico , Estudios Retrospectivos , Terapia de Inmunosupresión , Inmunosupresores/efectos adversos
8.
Allergy Asthma Proc ; 44(5): e22-e28, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37641226

RESUMEN

Background: Anti-thymocyte globulin (ATG) has been successfully used for decades to prevent graft versus host disease before hematopoietic stem cell transplantation (HSCT) as a part of conditioning regimen. However, sometimes hypersensitivity reactions may limit its use. Objective: To evaluate hypersensitivity reactions experienced during rabbit-ATG infusion among children and present successful desensitization protocol. Methods: The medical records of pediatric patients who were given rabbit-ATG treatment at our tertiary center hospital HSCT unit between 2019 and 2022 were reviewed retrospectively. Diagnosis of the patients, age at the time of HSCT, gender, presence of hypersensitivity reaction to rabbit-ATG, and management were evaluated. Characteristics of the reaction and presence of hypersensitivity reaction to other drugs were also noted. If performed, desensitization protocols were evaluated retrospectively. Results: We evaluated 81 patients; 66.6% of them (n = 54) were boys. The mean age of the patients was 8.78 ± 5.48 years. Hypersensitivity to rabbit-ATG was seen in six patients (7.4%). Four of them (4.9%) had anaphylaxis; two (2.4%) had urticaria. Intradermal test performed to every patient before the first dose of ATG infusion was detected a positive result in 1 patient (1.2%) . None of these seven patients had allergic reactions to other drugs before. Successful ATG desensitization was performed in five patients by using a 12-16 step protocol due to patients' reaction severity. Conclusion: This study aimed to evaluate hypersensitivity reactions with rabbit-ATG in children. A successful desensitization protocol with rabbit-ATG is presented. Desensitization must be performed with an experienced team very carefully in the absence of alternative drug.


Asunto(s)
Anafilaxia , Urticaria , Humanos , Suero Antilinfocítico/efectos adversos , Estudios Retrospectivos , Anafilaxia/diagnóstico , Anafilaxia/etiología , Anafilaxia/prevención & control , Pruebas Intradérmicas
9.
Transplant Proc ; 55(7): 1551-1554, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37414697

RESUMEN

BACKGROUND: Advances in immunosuppressive therapies and surgical techniques have led to a significant reduction in the incidence of rejection within 1 year after kidney transplantation. Immunologic risk is an important factor affecting graft functions and guiding the clinician in the selection of induction therapy. The aim of this study was to investigate graft functions based on serum creatinine levels, Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) and proteinuria levels, frequency of leukopenia, cytomegalovirus (CMV) and BK virus polymerase chain reaction (PCR) positivity in patients with low and high immunologic risk. MATERIAL AND METHODS: This retrospective study included 80 renal recipients. Recipients were divided into 2 groups: patients at low immunologic risk who received basiliximab only and those with high immunologic risk who received low-dose (1.5 mg/kg for 3 days) antithymocyte globulin and basiliximab. RESULTS: No significant differences were observed between the 2 risk groups in terms of first, third, sixth, and 12th-month creatinine levels, CKD-EPI, proteinuria levels, leukopenia frequency, and CMV and BK virus PCR positivity. CONCLUSION: One-year graft survivals did not differ significantly between these 2 treatment modalities. The combined use of low-dose antithymocyte globulin and basiliximab in the induction treatment of patients with high immunologic risk seems promising in terms of graft survival, leukopenia frequency, and CMV and BK virus PCR positivity.


Asunto(s)
Infecciones por Citomegalovirus , Insuficiencia Renal Crónica , Humanos , Basiliximab , Inmunosupresores/efectos adversos , Suero Antilinfocítico/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Estudios Retrospectivos , Quimioterapia de Inducción , Rechazo de Injerto , Supervivencia de Injerto , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/inducido químicamente , Insuficiencia Renal Crónica/inducido químicamente , Proteinuria/inducido químicamente , Proteínas Recombinantes de Fusión
10.
Exp Clin Transplant ; 21(5): 428-433, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37334690

RESUMEN

OBJECTIVES: The main risk factor for poor graft outcomes is refractory acute rejection and its consequences. In this study, we compared the efficacy of antithymocyte globulins versus other antirejection strategies in reversing refractory acute graft rejection after living donor renal transplant. MATERIALS AND METHODS: We retrospectively reviewed the records of 745 patients who received living-donor kidney transplants and experienced acute rejection episodes at Mansoura Urology and Nephrology Center in Egypt over the past 20 years. Based on the type of antirejection medication that they received, we divided patients into 2 groups, with 80 patients in the antithymocyte globulin group and 665 patients who had other antirejection strategies. By using event-based sequential graft biopsy histopathology analysis, we compared the efficacy of antithymocyte globulins in reversing refractory rejection in terms of graft and patient complications and survival. RESULTS: Patient survival was comparable in both groups; however, graft survival was better in the antithymocyte globulin group than in the other group; in addition, event-based sequential graft biopsies revealed a lower incidence of acute and chronic rejection episodes after treatment of severe acute rejection in the antithymocyte globulin group compared with the other group. Incidence of posttreatment complications, particularly infection and malignancy, was comparable in both groups. CONCLUSIONS: Our retrospective analysis of event-based sequential graft biopsy allowed us to track graft rejection resolution or worsening. Antithymocyte globulins are highly effective in reversing acute graft rejection when compared with other approaches, with no increased risk of infection or malignancy.


Asunto(s)
Suero Antilinfocítico , Trasplante de Riñón , Humanos , Suero Antilinfocítico/efectos adversos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/prevención & control , Rechazo de Injerto/patología , Supervivencia de Injerto , Biopsia , Resultado del Tratamiento
11.
Zhonghua Xue Ye Xue Za Zhi ; 44(3): 211-215, 2023 Mar 14.
Artículo en Chino | MEDLINE | ID: mdl-37356982

RESUMEN

Objective: To investigate the effect of on-demand glucocorticoid strategy on the occurrence and outcome of porcine anti-lymphocyte globulin (p-ALG) -associated serum sickness in aplastic anemia (AA) . Methods: The data of AA patients who received in the Anemia Diagnosis and Treatment Center of Haematology Hospital, CAMS & PUMC from January 2019 to January 2022 were collected. Among them, 35 patients were enrolled in the on-demand group, with the glucocorticoid strategy adjusted based on the occurrence and severity of serum sickness; 105 patients were recruited in the usual group by matching the age and disease diagnosis according to 1∶3 ratio in patients who received a conventional glucocorticoid strategy in the same period. The incidences, clinical manifestations, treatment outcomes of serum sickness, and glucocorticoid dosage between the two groups were analyzed. Results: The incidences of serum sickness in the on-demand group and the usual group were 65.7% and 54.3% (P=0.237) , respectively. The median onset of serum sickness was the same [12 (9, 13) d vs the 12 (10, 13) d, P=0.552], and clinical symptoms and signs, primarily joint, and/or muscle pain, fever, and rash were similar. Severity grades were both dominated by Grades 1-2 (62.8% vs 51.4%) , with only a few Grade 3 (2.9% vs 2.9%) , and no Grades 4-5. No significant difference in the serum sickness distribution (P=0.530) . The median duration of serum sickness was the same [5 (3, 7) d vs 5 (3, 6) d, P=0.529], and all patients were completely cured after glucocorticoid therapy. In patients without serum sickness, the average dosage of prophylactic glucocorticoid per patient in the usual group was (469.48 ±193.57) mg (0 in the on-demand group) . When compared to the usual group, the average therapeutic glucocorticoid dosage per patient in the on-demand group was significantly lower [ (125.91±77.70) mg vs (653.90±285.56) mg, P<0.001]. Conclusions: In comparison to the usual glucocorticoid strategy, the on-demand treatment strategy could significantly reduce glucocorticoid dosage without increasing the incidence of serum sickness; in addition, the duration of serum sickness and the incidence of above Grade 2-serum sickness were similar.


Asunto(s)
Anemia Aplásica , Globulinas , Enfermedad del Suero , Animales , Porcinos , Suero Antilinfocítico/efectos adversos , Enfermedad del Suero/inducido químicamente , Enfermedad del Suero/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Anemia Aplásica/tratamiento farmacológico , Resultado del Tratamiento , Globulinas/uso terapéutico
12.
Eur J Haematol ; 111(3): 407-413, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37271577

RESUMEN

AIMS: To compare cyclosporine (CSA) combining eltrombopag (EPAG) with or without antithymocyte globulin (ATG) in aplastic anemia (AA) patients in the real world. METHODS: AA patients who received ATG combining CSA and EPAG (Group A) and CSA + EPAG (Group B) as front-line treatment in 13 medical centers in China were enrolled. The efficacy and safety were compared. RESULTS: A total of 89 patients were enrolled with 51 patients in Group A and 38 patients in Group B. The 6-month overall response (OR)/complete response (CR) was 73.3%/24.4% and 60.6%/27.3% in Groups A and B (p > .1). For severe AA patients, the 6-month OR was 74.1% versus 50% and 6-month CR was 25.9% versus 20% in Groups A and B (p > 0.1). Multivariate analysis showed gender affects the 6-month OR with females better OR (p = .017, OR 6.045, 95% CI: 1.377-26.546) and time from disease onset to treatment affected the 12-month CR (p = .026, OR 0.263, 95% CI: 0.081-0.852). No difference was found in side effects except ATG infusion reaction and serum sickness. Mortality was 7.8% in Group A and no patient died in Group B. CONCLUSIONS: CSA + EPAG had a similar response and less side effects compared with standard immunosuppressive therapy + EPAG in newly diagnosed AA.


Asunto(s)
Anemia Aplásica , Ciclosporina , Femenino , Humanos , Ciclosporina/efectos adversos , Suero Antilinfocítico/efectos adversos , Anemia Aplásica/diagnóstico , Anemia Aplásica/tratamiento farmacológico , Estudios Retrospectivos , Inmunosupresores/efectos adversos , Resultado del Tratamiento
13.
Ann Hematol ; 102(6): 1569-1579, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37097455

RESUMEN

To compare the outcomes of patients with hematological malignancies who received ATG-Fresenius (ATG-F) 20 mg/kg versus those who received ATG-Genzyme (ATG-G) 10 mg/kg in an unrelated donor hematopoietic stem cell transplantation (HSCT) procedure, a total of 186 patients who underwent their first allogeneic HSCT with an unrelated donor were retrospectively analyzed. One hundred and seven patients received ATG-F, and seventy-nine patients received ATG-G. Multivariate analysis showed that the type of ATG preparation had no effect on neutrophil engraftment (P = 0.61), cumulative incidence of relapse (P = 0.092), nonrelapse mortality (P = 0.44), grade II-IV acute graft-versus-host disease (GVHD) (P = 0.47), chronic GVHD (P = 0.29), overall survival (P = 0.795), recurrence-free survival (P = 0.945) or GVHD-free relapse-free survival (P = 0.082). ATG-G was associated with a lower risk of extensive chronic GVHD and a higher risk of cytomegaloviremia (P = 0.01 and HR = 0.41, P < 0.001 and HR = 4.244, respectively). The results of this study suggest that the preparation of rabbit ATG used for unrelated HSCT should be selected based on the incidence of extensive chronic GVHD of each center, and the posttransplant management strategy should be adjusted according to the ATG preparation.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Animales , Conejos , Humanos , Estudios Retrospectivos , Donante no Emparentado , Trasplante Homólogo/efectos adversos , Recurrencia Local de Neoplasia/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Suero Antilinfocítico/efectos adversos , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/complicaciones , Acondicionamiento Pretrasplante/métodos
14.
Immunotherapy ; 15(5): 323-333, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36852421

RESUMEN

Aplastic anemia is a rare but potentially serious complication of immune checkpoint inhibitor therapy. The authors present a case of pembrolizumab-induced aplastic anemia that was refractory to steroids but had some hematologic response to modified-dosing antithymocyte globulin (ATG). This is the first reported case of hematological response to ATG for immune checkpoint inhibitor-induced aplastic anemia and the first reported case of modified ATG dosing for this indication. Cases of immune checkpoint inhibitor-induced aplastic anemia and management options are also summarized. Given the high morbidity and mortality associated with ICI-induced aplastic anemia, more data is necessary to guide evidence-based management recommendations.


Immune checkpoint inhibitors (ICIs) are a form of anticancer therapy that enlists the body's own immune system to fight cancer cells. Although remarkably effective against some types of cancer, ICIs can also cause the augmented immune system to attack noncancer cells, resulting in unwanted off-target side effects. One rare but potentially serious complication of ICIs is aplastic anemia, where the body stops producing enough new blood cells. There is little known about ICI-induced aplastic anemia. The authors present a case of ICI-induced aplastic anemia that did not improve with standard treatment but had some response to antithymocyte globulin, which has not been previously reported. Previously published cases of ICI-induced aplastic anemia and management options are also summarized.


Asunto(s)
Anemia Aplásica , Humanos , Anemia Aplásica/tratamiento farmacológico , Suero Antilinfocítico/efectos adversos , Inhibidores de Puntos de Control Inmunológico , Anticuerpos Monoclonales Humanizados/efectos adversos
15.
Intern Med ; 62(17): 2553-2557, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36725050

RESUMEN

Lymphoproliferative disorders and Epstein-Barr virus reactivation (EBV-LPDs) have various forms of onset, ranging from infectious mononucleosis-like syndrome (IM-like) to lymphoma, although whether or not IM-like progresses to lymphoma remains unclear. A 61-year-old man was diagnosed with aplastic anemia (AA). Polyclonal atypical B-lymphocytes were observed in the peripheral blood, and IM-like was diagnosed. Atypical lymphocytes disappeared, but a gastrointestinal examination revealed diffuse large B-cell lymphoma (DLBCL). Rituximab was initiated but later discontinued because of severe acute respiratory syndrome coronavirus 2 infection. Pancytopenia due to AA exacerbation recurred. The patient ultimately died of multiple organ failure due to bacterial infection.


Asunto(s)
Anemia Aplásica , COVID-19 , Infecciones por Virus de Epstein-Barr , Linfoma de Células B Grandes Difuso , Masculino , Humanos , Persona de Mediana Edad , Suero Antilinfocítico/efectos adversos , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/complicaciones , Herpesvirus Humano 4 , Infecciones por Virus de Epstein-Barr/diagnóstico , COVID-19/complicaciones , Recurrencia Local de Neoplasia/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones
16.
Ann Hematol ; 102(3): 503-517, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36622392

RESUMEN

Acquired aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia, and immunosuppressive therapy (IST) is the optional first-line management. Several studies identified the influencing factors on IST response; however, there are still a considerable number of patients suffering from poor prognoses. In this study, we enrolled 61 AA patients aged ≤ 40 years old, and whole-exome sequencing (WES) found unexpected high FANC heterozygous germline mutations (28/61, 45.9%). Patients with FANC mutations have a significantly lower absolute reticulocyte count and CD34+ % in the bone marrow and also lower 3-, 6-, and 9-month IST response than that without mutation, which were 0% vs. 25% (P = 0.017), 26.3% vs. 42.1% (P = 0.495), and 29.4% vs. 72.2% (P = 0.011), especially in anti-thymocyte globulin combined with the cyclosporin A (ATG + CsA) group, which were 0% vs.33.4% (P = 0.143), 25% vs.83.3% (P = 0.103), and 25% vs. 100% (P = 0.003), respectively. The event-free survival in the FANCwt group was also better than that in the FANCmut group (P = 0.016) and also showed in patients who received ATG + CsA treatment (P = 0.045). In addition, all the adverse effects of FANC germline mutation were not significant in stem cell-transplanted group. Our result indicated that the WES-based detection of FANC heterozygous germline mutations may have a great meaning in predicting IST response of acquired AA. This study was registered at chictr.org.cn (# ChiCTR2100054992).


Asunto(s)
Anemia Aplásica , Proteínas del Grupo de Complementación de la Anemia de Fanconi , Pancitopenia , Adulto , Humanos , Anemia Aplásica/terapia , Suero Antilinfocítico/efectos adversos , Ciclosporina/efectos adversos , Pueblos del Este de Asia , Secuenciación del Exoma , Mutación de Línea Germinal , Terapia de Inmunosupresión , Inmunosupresores/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética
17.
Int J Hematol ; 117(1): 37-43, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36441357

RESUMEN

Aplastic anemia results from lymphocyte-mediated destruction of hematopoietic stem cells. Immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporine is the standard front-line treatment for patients with severe aplastic anemia who are not suitable candidates for stem cell transplants. PF-06462700 is a potent equine ATG that targets T-lymphocytes and has been approved as a treatment for aplastic anemia outside of Japan for over 30 years. Due to the high medical need for PF-06462700, the Ministry of Health, Labor and Welfare requested its development for Japanese patients with aplastic anemia. In this case series, the efficacy and safety of PF-06462700, administered intravenously at 40 mg/kg/day for 4 days, were assessed over a 24-week period. This was as an open-label, single-arm, multicenter clinical study designed to enroll a minimum of three Japanese participants with aplastic anemia. Two participants met the primary outcome of hematologic response at week 12 and improvements in disease severity were observed. No deaths or serious adverse events were reported. The efficacy results from this case series suggest that administration of PF-06462700 is generally well-tolerated and produces a hematologic response in Japanese patients with aplastic anemia, which should be further evaluated in real-world studies.ClinicalTrials.gov identifier: NCT04350606.


Asunto(s)
Anemia Aplásica , Suero Antilinfocítico , Humanos , Animales , Caballos , Suero Antilinfocítico/efectos adversos , Anemia Aplásica/tratamiento farmacológico , Pueblos del Este de Asia , Ciclosporina , Linfocitos T , Inmunosupresores/efectos adversos , Resultado del Tratamiento
18.
Ann Transplant ; 27: e937688, 2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36193015

RESUMEN

BACKGROUND Renal transplant recipients are susceptible to increased mortality with COVID-19 infection. There is insufficient data regarding risk factors for COVID-19 disease acquisition. We aimed to identify them here. MATERIAL AND METHODS We enrolled Pakistani renal transplant recipients from February 10, 2020, to March 18, 2021, and actively tracked their baseline health status, transplant characteristics, comorbidities, immunosuppressive therapies, and post-transplant follow-ups until September 2021. Furthermore, we formulated 2 questionnaires for their compliance assessment with COVID-19-preventive measures. We also identified COVID-19 disease acquisition, symptomatology, and management. RESULTS Among the 50 enrolled patients, 14 (28%) patients developed COVID-19, which is higher than the incidence observed in general Pakistani population (0.55%). Their mean age was 35.38 years ±11.69 SD years, and 82% of patients were males. The following factors were independently associated with COVID-19 disease: female gender (P value: 0.042), diabetes mellitus (P value: 0.002), anti-thymocyte globulin (ATG) induction (P value: 0.006), in-person follow-ups (P value: 0.000), prolonged immediate and late post-transplant hospital stays (P value: 0.019 and 0.000, respectively), raised post-transplant serum creatinine (P value: 0.019), and COVID-19 protective measures non-compliance (P value: 0.000). Out of 14 infected recipients, 92.85% required symptomatic management and overall mortality was 0%. CONCLUSIONS Female gender, diabetes mellitus, ATG induction, in-person follow-ups, prolonged hospital stays, raised post-transplant serum creatinine, and COVID-19-protective measures non-compliance were associated with the higher acquisition of SARS-CoV-2 infection. By taking concrete measures against these risk factors, we can continue renal transplants, as overall mortality was lower than in the general Pakistani population (2%).


Asunto(s)
COVID-19 , Diabetes Mellitus , Trasplante de Riñón , Adulto , Suero Antilinfocítico/efectos adversos , COVID-19/epidemiología , Creatinina , Diabetes Mellitus/etiología , Femenino , Humanos , Incidencia , Trasplante de Riñón/efectos adversos , Masculino , Pakistán/epidemiología , Factores de Riesgo , SARS-CoV-2 , Receptores de Trasplantes
19.
Nephrology (Carlton) ; 27(11): 901-905, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36047901

RESUMEN

To describe an experience using a protocol using de novo belatacept (DNB) based maintenance immunosuppression in the setting of lymphocyte depletion. A retrospective, observational study was performed on 37 kidney transplant recipients treated with the DNB protocol, which was defined as belatacept initiated within 7 days after a kidney transplant with steroids and mycophenolate with anti-thymocyte globulin (ATG) induction without concomitant calcineurin inhibitors (CNIs). Patients who received a deceased donor kidney meeting one or more of the following criteria: anticipated cold ischemia time (CIT) greater than 24 h, donation after cardiac death, donor acute kidney injury, and a Kidney Donor Profile Index (KDPI) >85% during the study period were included. Patient survival at 1 year was 97.3% and graft survival was 94.6%. Delayed graft function (DGF) occurred in 40.54% of the patients. Two patients experienced a Banff 1B acute cellular rejection. BK viremia was detected in 32.4% of patients. The mean estimated glomerular filtration rate (eGFR) calculated with the use of modification of diet in renal disease (MDRD) equation at 1 year in the study group was 54.7 ml/min/1.73 m2 . We believe that utilization of the DNB protocol, which allows early CNI avoidance, may decrease organ discard rates.


Asunto(s)
Suero Antilinfocítico , Inhibidores de la Calcineurina , Abatacept/efectos adversos , Aloinjertos , Suero Antilinfocítico/efectos adversos , Inhibidores de la Calcineurina/efectos adversos , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Inmunosupresores/efectos adversos , Riñón , Estudios Retrospectivos , Esteroides
20.
Transplant Proc ; 54(8): 2133-2139, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36116944

RESUMEN

BACKGROUND: Induction immunosuppression is used to reduce the incidence of acute rejection and prevent delayed graft function. The 2 rabbit anti-thymocyte globulins- thymoglobulin and Grafalon (ATG Fresenius) have been commonly used for induction immunosuppression and treatment of acute rejection in solid organ transplantation. There are very few studies comparing the efficacy and side effects of both the anti-thymocyte globulins therefore this prospective study comparing the 2 types of anti-thymocyte globulins would be of clinical interest. PATIENTS AND METHODS: This prospective single center study was conducted at Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, India from April 2019 to June 2020. Sixty-two ABO-compatible renal transplant recipients were included in the study. They were divided in 2 groups of 31 patients each. One group received thymoglobulin (3 mg/kg) and the second group received Grafalon (6 mg/kg). All patients were followed up for 12 months and the 2 groups were compared for incidence of rejections, infections, graft function, patient survival, and graft survival. RESULTS: There was no significant difference in the incidence of rejections, infective episodes, graft function, posttransplant diabetes mellitus, graft survival and patient survival in thymoglobulin or Grafalon groups. The hematological parameters were similar in both groups at 7 days, 1 month, and 6 months of follow-up. The absolute lymphocyte count was significantly lower in the thymoglobulin group at 12 months posttransplant. CONCLUSIONS: Thymoglobulin and Grafalon were found to be equivalent in terms of safety and efficacy in short term, with no difference in rejections, infections, graft survival, or patient survival.


Asunto(s)
Suero Antilinfocítico , Trasplante de Riñón , Suero Antilinfocítico/efectos adversos , Trasplante de Riñón/efectos adversos , Estudios Prospectivos , Rechazo de Injerto/epidemiología , Inmunosupresores/efectos adversos , Supervivencia de Injerto
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