RESUMEN
A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.
Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Estudios Retrospectivos , Neutrófilos , Estudios Prospectivos , Enfermedad Injerto contra Huésped/etiología , Terapia de Inmunosupresión , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento PretrasplanteRESUMEN
BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) clone can be detected in some patients with aplastic anemia (AA) before treatment. But the prognostic value of the presence of pre-treatment PNH clone for intensive immunosuppressive therapy (IIST) is controversial and no consensus on whether the occurrence of PNH/AA-PNH syndrome is related to pre-treatment PNH clone. OBJECTIVE: This study aims to summarize the prognostic value of the presence of pre-treatment PNH clone treated with IIST among the AA patients and to elucidate its relationship with the development of PNH / AA-PNH syndrome. METHODS: All published studies on the prognostic value of pre-treatment PNH clone among AA patients were retrieved. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant. RESULTS: The meta-analysis consisted of 15 studies with a combined total of 1349 patients in the cohort. Pre-treatment PNH clone had a positive effect on AA patients 6-month (pooled OR = 1.49,95% Cl: 1.06-2.08, P = 0.020), 12-month (pooled OR = 3.10,95% Cl: 1.89-5.10, P = 0.000), and overall hematological response rate (pooled OR = 1.69,95% Cl: 1.07-2.68, P = 0.024) after IIST. Patients with pre-treatment PNH clone are more likely to develop PNH/AA-PNH syndrome after IIST(pooled OR = 2.78,95%Cl:1.21-6.39, P = 0.016). CONCLUSION: Patients with positive pre-treatment PNH clone had better hematological responses to IIST than negative. And, those patients are more likely to develop PNH/AA-PNH syndrome after IIST.
Asunto(s)
Anemia Aplásica , Hemoglobinuria Paroxística , Humanos , Anemia Aplásica/tratamiento farmacológico , Hemoglobinuria Paroxística/tratamiento farmacológico , Pronóstico , Terapia de Inmunosupresión , Células Clonales , SíndromeRESUMEN
Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, P=0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, P=0.004), red cell distribution width - coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, P=0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, P=0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×109/L, 11.75%, and 1.06×109/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895). Clinical Trial Registration: http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.
Asunto(s)
Anemia Aplásica , Anemia Aplásica/tratamiento farmacológico , Animales , Suero Antilinfocítico , Benzoatos , Ciclosporina/uso terapéutico , Humanos , Hidrazinas , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Pirazoles , Conejos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Immunosuppressive therapy (IST) is an effective treatment regimen for severe aplastic anaemia (SAA) patients without HLA-identical donors. This study further compared the outcomes between IST and IIST-UCB in SAA on the basis of research shown that IST combined with umbilical cord blood infusion (IIST-UCB) treated effectively. A total of 123 patients from 11 hospitals in China were enrolled. Sixty-nine patients in IIST-UCB group were treated with ATG + CsA + CTX combined with cord blood, while 54 patients in IST group with ATG + CsA. The overall remission rates (ORRs), complete remission (CR) rates and partial response (PR) rates of IIST-UCB group and IST group at 3 months were 69.67% vs 51.85% (P = .045), 21.74% vs 3.7% (P = .004) and 47.83% vs 48.15% (P = .972), respectively. After 6 months of treatment, they were 76.81% vs 57.41% (P = .022), 37.68% vs 11.11% (P = .001) and 39.13% vs 46.30% (P = .425), respectively. After 1 year of treatment, they were 85.51% vs 61.11% (P = .002), 59.42% vs 25.93% (P = .000) and 26.09% vs 35.19% (P = .275), respectively. The ORRs and CR rates of IIST-UCB group were both significantly higher than IST group after 3 months, 6 months and 1 year of treatment. The neutrophil granulocyte, platelet and haemoglobin recovery times of IIST-UCB group were significantly shorter than IST group. Compared with standard IST, IIST-UCB as an effective therapy for SAA patients without HLA-identical donors accelerated the haematopoietic reconstitution, resulting in higher early CR rates.
Asunto(s)
Anemia Aplásica , Anemia Aplásica/tratamiento farmacológico , Suero Antilinfocítico , Ciclofosfamida , Ciclosporina , Sangre Fetal , Humanos , Terapia de Inmunosupresión , Inmunosupresores/efectos adversos , Resultado del TratamientoRESUMEN
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a matched sibling donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are 2 major comparable treatments for SAA. As the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin or porcine-antilymphocyte globulin, cyclosporine plus eltrombopag. The results suggested that patients treated with MSD-HSCT or IST/EPAG had similar overall survival (OS) rates exceeding 95% (Pâ¯=â¯.97). However, the event-free survival rate (EFS) of IST/EPAG (71.0%) was significantly lower than that of MSD-HSCT (89.6%), Pâ¯=â¯.04. Subgroup analysis indicated that the OS of the MSD-HSCT group was superior to that of the IST/EPAG group (100% versus 85.7%, Pâ¯=â¯.04) among those with very severe aplastic anemia (VSAA). Both the complete response rate (CR) and overall response rate (OR) with MSD-HSCT were significantly higher than those with IST/EPAG (CR: 79.2% versus 15.7%, P < .001; OR: 97.9% versus 72.6%, Pâ¯=â¯.001). In conclusion, IST/EPAG or MSD-HSCT treatment achieves an equally high OS in SAA, but MSD-HSCT leads to a better OS in patients with VSAA and shows advantages in improving EFS and accelerating hematopoietic reconstruction in patients with SAA.
Asunto(s)
Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Animales , Benzoatos , Humanos , Hidrazinas , Terapia de Inmunosupresión , Pirazoles , Hermanos , PorcinosRESUMEN
The influence of chronic hepatitis B virus (HBV) infection on the efficacy of intensive immunosuppressive treatment (IST) of severe aplastic anaemia (SAA) patients remains unclear. Previous reports on this topic have been mostly case reports or have had a relatively short follow-up. Eight SAA patients carrying chronic HBV infection and 24 matched patients without HBV at a ratio of 1:3 were included in this retrospective analysis. The patients were treated with anti-thymocyte globulin (ATG) and cyclosporine A. Entecavir was or was not administered throughout the IST course to patients with positive or negative HBV-DNA results, respectively. No evident HBV reactivation developed. The overall response was 87.5% by 12 months, and the recurrence rate was 12.5%. There were no significant differences in overall response, overall survival and event-free survival between groups. Entecavir can effectively prevent reactivation of HBV in SAA patients with positive HBV-DNA who received intensive IST. Regular surveillance may be sufficient for HBV-DNA negative patients who should receive antiviral drugs immediately when their HBV-DNA status changes from negative to positive. The prognosis of SAA patients with chronic HBV infection after intensive IST treatment is not worse than those without HBV infection.