Immune thrombocytopenia (ITP) results from platelet destruction and production suppression. Eltrombopag belongs to a new class of thrombopoietin-mimetic drugs that raise platelet counts in ITP ...patients. We performed a single-arm study to assess the response to a single course of dexamethasone (40 mg by mouth, days 1-4) in combination with eltrombopag (50 mg, days 5-32) in 12 adults with newly diagnosed ITP in an outpatient setting. Median follow-up was 12.5 months. After therapy (day 33), 100% of patients achieved at least ≥30 × 109/L platelets. Four patients relapsed. Complete response at 6 months (platelets ≥100 × 109/L) was achieved in 50% of patients and response at 6 months (platelets ≥30 <100 × 109/L) was achieved in another 25%; relapse-free survival was 66.7% at 12 months (median response duration of 8.3 months). In conclusion, eltrombopag/dexamethasone is a feasible frontline therapy for ITP. This trial is registered at www.clinicaltrials.gov as NCT01652599.
•Eltrombopag/dexamethasone is a safe and effective combination for treating newly diagnosed ITP patients.•This treatment may prove useful in achieving lasting responses without additional immunosuppression in some patients.
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.
•Patient navigation is a process that helps patients overcome barriers to transplantation.•Collaboration with nonprofit patient support organizations is key.•Telemedicine is a useful tool for patient ...navigation in low- and middle-income countries.
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.
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.
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.
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.
•Hispanics with ALL have increased risk of relapse and complications.•Intensive pediatric-inspired regimens are the standard of care for B-ALL in adolescents and young adults.•Administering a ...modified, low-cost regimen focused on outpatient administration was safe, feasible and effective in a patient cohort in Mexico.•Outcomes are still limited by treatment adherence and affordability.
B-cell acute lymphoblastic leukemia is frequent in Hispanic adolescents and young adults. Outcomes of implementation of pediatric-inspired regimens in low-and middle-income countries are not well known.
In this study we treated 94 adolescents and young adults with a local BFM regimen designed to be affordable with the use of native L-asparaginase and mitoxantrone administered in an outpatient fashion, and the of BCR/ABL and measurable residual disease (MRD) determined by high sensitivity flow cytometry for risk stratification.
Induction mortality was 11%; 25% of patients had to abandon treatment or be transferred to another health system. Two-year overall (OS) and event free survival (EFS) were 61.5% and 49.8%, MRD-negative patients had a 24-month OS of 85.6% vs. 69.6% (p = .024) and EFS of 76% vs. 45.5% (p = .004). Patients older than 40 years and those who abandoned treatment had worse EFS. Overall drug costs in our regimen were 52% lower than those of CALGB10403.
The treatment of AYAs with ALL with an outpatient focus was implemented successfully at a reduced cost. Genetic risk assessment, treatment abandonment and lack of access to novel therapies remain major barriers for improving outcomes.
This study originated due to the need of more efficient, cost-effective, and ambulatory regimens for adolescents and AYAs with ALL. Patients received a modified pediatric inspired regimen adjusted for maximum affordability. We have treated 94 patients this treatment with an outpatient focus has shown the possibility to implement low-cost treatment strategies for LLA in young patients in middle and low-income countries.
Danazol as first-line therapy for aplastic anemia Jaime-Pérez, José Carlos; Colunga-Pedraza, Perla R.; Gómez-Ramírez, Cynthia D. ...
Annals of hematology,
05/2011, Letnik:
90, Številka:
5
Journal Article
Recenzirano
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.
ABSTRACT
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.
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.
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.
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.
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.
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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