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Journal of Assisted Reproduction and... Jan 2023Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia and asthenozoospermia, and analyze changes in various evaluation indicators at different busulfan doses over time.
METHODS
We searched the Cochrane Library, PubMed databases, Web of Science, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until April 9, 2022. Animal experiments of busulfan-induced spermatogenesis dysfunction were included and screened. The model mortality and parameters of the evaluation indicators were subjected to meta-analysis.
RESULTS
Twenty-nine animal studies were included (control/model: 669/1829). The mortality of mice increased with busulfan dose. Significant spermatogenesis impairment occurred within 5 weeks, regardless of busulfan dose (10-40 mg/kg). Testicular weight (weighted mean difference [WMD]: - 0.04, 95% CI: - 0.05, - 0.03), testicular index (WMD: - 2.10, 95% CI: - 2.43, - 1.76), and Johnsen score (WMD: - 4.67, 95% CI: - 5.99, - 3.35) were significantly decreased. The pooled sperm counts of the model group were reduced by 32.8 × 10/ml (WMD: - 32.8, 95% CI: - 44.34, - 21.28), and sperm motility decreased by 37% (WMD: - 0.37, 95% CI: - 0.47, - 0.27). Sperm counts decreased slightly (WMD: - 3.03, 95% CI: - 3.42, - 2.64) in an intratesticular injection of low-dose busulfan (4 - 6 mg/kg), and the model almost returned to normal after one seminiferous cycle.
CONCLUSION
The model using low-dose busulfan (10 - 20 mg/kg) returned to normal after 10 - 15 weeks. However, in some spermatogenesis cycles, testicular weight reduction and testicular spermatogenic function damage were not proportional to busulfan dose. Sperm counts and motility results in different studies had significant heterogeneity. Standard protocols for sperm assessment in animal models were needed to reduce heterogeneity between studies.
Topics: Humans; Mice; Male; Animals; Oligospermia; Busulfan; Asthenozoospermia; Sperm Count; Sperm Motility; Semen
PubMed: 36508035
DOI: 10.1007/s10815-022-02674-y -
Bone Marrow Transplantation Feb 2023The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation... (Meta-Analysis)
Meta-Analysis
Myeloablative conditioning regimens in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission: a systematic review and network meta-analysis.
The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation (allo-HSCT) in complete remission (CR) remain unclear. We performed a systematic review and network meta-analysis to compare the effects of different MAC regimens. Bayesian network meta-analysis was performed using WinBUGS version 1.4.3. The commonly used MAC regimen Bu/Cy (4-day busulfan for toal 16 mg/kg orally or 12.8 mg/kg intravenously, plus 2-day cyclophosphamide for toal 120 mg/kg intravenously) is chosen as the common comparator. Pooled hazard ratios (HRs) with the associated 95% credibility interval (95% CrI) are obtained for all comparisons. We included 19 eligible studies, involving 8104 AML patients and 9 MAC regimens. Compared with Bu/Cy, 3-day busulfan plus fludarabine and thiotepa (Bu3/Flu/TT) is associated with significantly better overall survival (HR, 0.70; 95% CrI, 0.51 to 0.96) and lower risk of relapse (HR, 0.59; 95% CrI, 0.35 to 0.98). Bu3/Flu/TT is also associated with superior overall survival than Cy/TBI (cyclophosphamide plus total body irradiation), and lower risk of relapse than Bu4/Flu (4-day busulfan plus fludarabine). These results suggest that thiotepa-based new MAC regimen Bu3/Flu/TT is associated with improved outcomes in AML patients undergoing allo-HSCT in CR and worth further investigation.
Topics: Humans; Adult; Busulfan; Thiotepa; Bayes Theorem; Network Meta-Analysis; Transplantation, Homologous; Graft vs Host Disease; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Recurrence; Retrospective Studies; Transplantation Conditioning
PubMed: 36357773
DOI: 10.1038/s41409-022-01865-6 -
Cancer Immunology, Immunotherapy : CII Apr 2023T cell receptor-engineered T cell (TCR-T) therapy has shown promising efficacy in advanced solid tumours. Lymphodepleting (LD) chemotherapy improves TCR-T cell therapy... (Meta-Analysis)
Meta-Analysis Review
Lymphodepleting chemotherapy practices and effect on safety and efficacy outcomes in patients with solid tumours undergoing T cell receptor-engineered T cell (TCR-T) Therapy: a systematic review and meta-analysis.
BACKGROUND
T cell receptor-engineered T cell (TCR-T) therapy has shown promising efficacy in advanced solid tumours. Lymphodepleting (LD) chemotherapy improves TCR-T cell therapy efficacy but is associated with significant toxicities. Evidence is sparse regarding the optimum LD regimen for TCR-T cell therapy in solid tumours.
METHODS
A systematic review was conducted of interventional, prospective clinical trials describing LD practices prior to TCR-T cell therapy in patients with advanced solid tumours. The objective was to define LD regimens administered prior to TCR-T cell therapy and their effects on specific safety and efficacy outcomes in this patient population.
RESULTS
Searches returned 484 studies, 19 (231 patients) met the eligibility criteria. Cyclophosphamide (cyclo) 60 mg/kg daily (2 days), plus fludarabine (fludara) 25 mg/m daily (5 days) was the most common LD regimen (38% of studies). Higher dose LD regimens were associated with increased pooled incidence rates of febrile neutropaenia compared to low dose (0.64, [95% Confidence interval (CI): 0.50-0.78], vs. 0.39 [95% CI: 0.25-0.53], respectively) but were not significantly associated with higher objective responses (odds ratio: 1.05, 95%CI: 0.60-1.82, p = 0.86). A major shortfall in safety data reporting was identified; determination of LD regimen effects on many safety outcomes was not possible.
CONCLUSION
Standard consensus guidelines for the design and reporting of adoptive cell therapy (ACT) studies would facilitate accurate risk-benefit analysis for optimising LD regimens in patients with advanced solid tumours.
Topics: Humans; Prospective Studies; Neoplasms; Cyclophosphamide; Receptors, Antigen, T-Cell; T-Lymphocytes
PubMed: 36315268
DOI: 10.1007/s00262-022-03287-1 -
Clinical Advances in Hematology &... Oct 2022Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal... (Review)
Review
BACKGROUND
Several treatment strategies for amyloid light chain cardiac amyloidosis (AL-CA) have been described in the literature; however, there is no consensus about the optimal approach to AL-CA.
OBJECTIVE
We conducted this systematic review to summarize current evidence from published studies about the safety and efficacy of various treatment regimens for patients with AL-CA, mainly focusing on autologous stem cell transplant (ASCT) and heart transplant.
METHODS
An electronic literature search of PubMed, Web of Science, Scopus, EBSCO, and CINAHL Plus was conducted through December 2019 using the relevant keywords and prespecified MeSH terminology. Records were screened, and eligible studies were selected and narratively discussed. Data on the hematologic and cardiac responses as well as the safety of the treatment regimens were extracted and synthesized narratively in the context of the systematic review.
RESULTS
Thirty published articles were included in this systematic review. The most commonly used first-line treatment in the included studies was bortezomib-based therapy followed by high-dose melphalan and ASCT, with recent evidence of improved outcome with the addition of daratumumab. Heart transplant was found to extend survival for selected patients who were not eligible for ASCT; however, it was found to affect the patients' tolerance of further chemotherapy in some studies. Published data on longterm outcomes with immunomodulatory agents were scarce.
CONCLUSION
Current evidence suggests several possible regimens for the treatment of AL-CA. Effective treatment approaches for AL-CA include induction therapy with bortezomib-based or immunotherapy-based combinations in moderate/severe forms of cardiac involvement, followed by high-dose melphalan and ASCT in eligible patients, and heart transplant for selected severe cases. Therefore, we highlight the necessity of conducting well-designed, randomized controlled trials to provide evidence about the efficacy of these drugs with respect to ASCT.
Topics: Bortezomib; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Melphalan; Transplantation, Autologous; Treatment Outcome
PubMed: 36206073
DOI: No ID Found -
Oxidative Medicine and Cellular... 2022Chagas disease is an anthropozoonosis caused by the protozoan and is characterized as a neglected disease. It is currently endemic in 21 countries on the Latin American... (Review)
Review
Chagas disease is an anthropozoonosis caused by the protozoan and is characterized as a neglected disease. It is currently endemic in 21 countries on the Latin American continent, including Bolivia, Argentina, and Paraguay. Unfortunately, there are no optimally effective treatments that can reduce the damage caused in the digestive form of the disease, such as the neuronal destruction of the myenteric plexus of both the esophagus and the colon. Therefore, the objective of this systematic review was to report the possible pharmacological neuroprotective agents that were tested in murine models of the digestive form of Chagas disease. Inclusion criteria are experimental studies that used different murine models for digestive forms of Chagas disease related to pharmacological interventions with neuroprotective potential, without year and language restriction. On the other hand, the exclusion criteria were studies that did not approach murine models with the digestive form of the disease or did not use neuroprotective treatments, among others. The search in the PubMed, Web of Science, Embase, and LILACS databases was performed on September 4, 2021. In addition, a manual search was performed using the references of the included articles. The risk of bias assessment of the studies was performed based on the SYRCLE tool guidelines, and the data from the selected articles are presented in this review as a narrative description and in tables. Eight articles were included, 4 of which addressed treatment with acetylsalicylic acid, 3 with cyclophosphamide, and 1 with Lycopodium clavatum 13c. In view of the results of the studies, most of them show neuroprotective activity of the treatments, with the potential to reduce the number of damaged neurons, as well as positive changes in the structure of these cells. However, more studies are needed to understand the mechanisms triggered by each drug, as well as their safety and immunogenicity. Systematic review registration is as follows: PROSPERO database (CRD42022289746).
Topics: Animals; Aspirin; Chagas Disease; Cyclophosphamide; Humans; Mice; Neuroprotective Agents; Trypanosoma cruzi
PubMed: 36199427
DOI: 10.1155/2022/9397290 -
Medicine Sep 2022Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and feasibility of R-CHOP and DA-EPOCH-R as the first-line therapy for patients with DEL is urgently needed.
METHODS
The clinical and treatment outcomes of 75 DEL patients were retrospectively analyzed. The role of DA-EPOCH-R was determined and compared to that of R-CHOP in DEL patients. PubMed, Embase, the Cochrane Central Library, and ClinicalTrials.gov were systematically searched up to November 1, 2021 and were evaluated by Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles comparing DA-EPOCH-R versus R-CHOP in patients with DEL were included.
RESULTS
Overall, 49 and 26 DEL patients received R-CHOP and DA-EPOCH-R, respectively. Although the difference in response for patients who received R-CHOP and DA-EPOCH-R was not significant (P = .347), DA-EPOCH-R may improve the prognosis compared to R-CHOP (P = .056 for progression-free survival [PFS], P = .009 for overall survival [OS]). A systematic review and meta-analysis including 412 DEL patients in six articles were conducted. The event rate for 3-year PFS was significantly lower in patients receiving DA-EPOCH-R treatment than in those undergoing R-CHOP treatment (OR = 0.63, 95% CI = 0.42-0.94, P = .02), whereas no statistically significant difference was found in the HRs for both PFS and OS or the event rate for 3-year OS.
CONCLUSION
The results of this study indicated that DA-EPOCH-R might improve the prognosis of DEL patients compared with R-CHOP.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Prognosis; Retrospective Studies; Rituximab; Vincristine
PubMed: 36197215
DOI: 10.1097/MD.0000000000030620 -
International Urology and Nephrology Mar 2023Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of... (Meta-Analysis)
Meta-Analysis Review
Efficacy of low or heavy rituximab‑based protocols and comparison with seven regimens in idiopathic membranous nephropathy: a systematic review and network meta-analysis.
OBJECTIVE
Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of rituximab for IMN are still controversial. This network meta-analysis (NMA) was conducted to compare the efficacy of different rituximab dosages and other main treatments in IMN treatment.
METHODS
Randomized controlled trials (RCTs) and observational studies analyzing nine therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR) and relapse rate. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions.
RESULTS
Twelve RCTs and 12 observational studies involving 1724 patients were pooled for comparison of 9 interventions. This NMA demonstrated steroids + tacrolimus was ranked first in the aspect of total remission at 6 months (92%) and 12 months (81.3%). The total remission rate associated with tacrolimus + rituximab increased rapidly between the sixth (SUCRA 22.5%) and the twelfth month (SUCRA 63.9%). Tacrolimus and cyclosporine A were associated with higher total remission at 6 months (78.8% and 65.4%, separately) and decreased at 12 months (58.1 and 34.9%, separately). Steroids + cyclophosphamide, rituximab (Heavy dose) and rituximab (Low dose) had stable remission rates at 6 (63.7%, 46.6%, and 19.4%) and 12 months (SUCRA 66.9%, 39.6%, and 28.8%). Tacrolimus and cyclosporine A were associated with a significantly higher risk of relapse than that with steroids + cyclophosphamide, rituximab (Heavy dose), and rituximab (Low dose).
CONCLUSIONS
For IMN in adults, steroids + tacrolimus was ranked first in the aspect of total remission, followed by steroids + cyclophosphamide and steroids + cyclosporine A. The TR associated with rituximab (Heavy and Low dosage) at 12 months was higher than that at 6 months. And rituximab (Heavy dose) achieves a higher rate of total remission than that of rituximab (Low dose).
Topics: Adult; Humans; Cyclophosphamide; Cyclosporine; Glomerulonephritis, Membranous; Immunosuppressive Agents; Network Meta-Analysis; Rituximab; Tacrolimus; Treatment Outcome
PubMed: 36161550
DOI: 10.1007/s11255-022-03372-5 -
International Journal of Hematology Oct 2022The successful application of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis in HLA-haploidentical allogeneic hematopoietic...
The successful application of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis in HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT) led to the expansion of its application to HLA-matched related and unrelated allo-HCT. Notably, single-agent PTCy was found to be feasible for GVHD prevention in HLA-matched bone marrow transplantation. Single-agent PTCy prophylaxis was later attempted to control GVHD in HLA-matched peripheral blood stem cell transplantation (PBSCT), but this approach was inadequate to alleviate GVHD as evidenced by the high incidence of severe GVHD and/or non-relapse mortality. Therefore, various combinations of immunosuppressants with PTCy have been explored to identify the optimal drug combination that would efficiently prevent GVHD in HLA-matched PBSCT. A recent murine study helped clarify the putative mechanism underlying the activity of PTCy, demonstrating that PTCy impairs the proliferation and function of alloreactive T cells from the donor, but does not eliminate alloreactive T cells altogether. In addition, imbalanced reconstitution of NK cell as well as T cells has been observed in HLA-haploidentical allo-HCT. Therefore, it remains unclear whether or not PTCy-containing GVHD prophylaxis should replace the classical GVHD prophylaxis regimen in the HLA-matched setting, and convincing evidence supporting the benefits of PTCy is needed.
Topics: Animals; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Mice; Peripheral Blood Stem Cell Transplantation
PubMed: 35930118
DOI: 10.1007/s12185-022-03428-3 -
Clinical Rheumatology Dec 2022Takayasu arteritis (TAK) is a less common large-vessel vasculitis which can occur in either children or adults. However, differences between pediatric-onset and... (Meta-Analysis)
Meta-Analysis Review
Takayasu arteritis (TAK) is a less common large-vessel vasculitis which can occur in either children or adults. However, differences between pediatric-onset and adult-onset TAK have not been systematically analyzed. We undertook a systematic review (pre-registered on PROSPERO, identifier CRD42022300238) to analyze differences in clinical presentation, angiographic involvement, treatments, and outcomes between pediatric-onset and adult-onset TAK. We searched PubMed (MEDLINE and PubMed Central), Scopus, major recent international rheumatology conference abstracts, Cochrane database, and clinicaltrials.gov, and identified seven studies of moderate to high quality comparing pediatric-onset and adult-onset TAK. Meta-analysis of 263 pediatric-onset and 981 adult-onset TAK suggested that constitutional features (fever, and in subgroup analyses, weight loss), hypertension, headache, and sinister features of cardiomyopathy, elevated serum creatinine, and abdominal pain were more frequent in pediatric-onset TAK, whereas pulse loss/pulse deficit and claudication (particularly upper limb claudication) were more frequent in adult-onset TAK. Hata's type IV TAK was more common in pediatric-onset TAK, and Hata's type I TAK in adult-onset TAK. Children with TAK also appeared to require more intense immunosuppression with more frequent use of cyclophosphamide, biologic DMARDs, tumor necrosis factor alpha inhibitors, and, in subgroup analyses, tocilizumab in pediatric-onset TAK than in adult-onset TAK. Surgical or endovascular procedures, remission, and risk of mortality were similar in both children and adults with TAK. No studies had compared patient-reported outcome measures between pediatric-onset and adult-onset TAK. Distinct clinical features and angiographic extent prevail between pediatric-onset and adult-onset TAK. Clinical outcomes in these subgroups require further study in multicentric cohorts.
Topics: Child; Adult; Humans; Takayasu Arteritis; Retrospective Studies; Cyclophosphamide; Immunosuppression Therapy; Antirheumatic Agents
PubMed: 35927524
DOI: 10.1007/s10067-022-06318-5 -
The Cochrane Database of Systematic... Jul 2022Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.
OBJECTIVES
To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).
SEARCH METHODS
We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February 2022.
SELECTION CRITERIA
We included RCTs that compared HSCT to immunomodulators in the treatment of SSc.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence using standard Cochrane methods.
MAIN RESULTS
We included three RCTs evaluating: non-myeloablative non-selective HSCT (10 participants), non-myeloablative selective HSCT (79 participants), and myeloablative selective HSCT (36 participants). The comparator in all studies was cyclophosphamide (123 participants). The study examining non-myeloablative non-selective HSCT had a high risk of bias given the differences in baseline characteristics between the two arms. The other studies had a high risk of detection bias for participant-reported outcomes. The studies had follow-up periods of one to 4.5 years. Most participants had severe disease, mean age 40 years, and the duration of disease was less than three years. Efficacy No study demonstrated an overall mortality benefit of HSCT when compared to cyclophosphamide. However, non-myeloablative selective HSCT showed overall survival benefits using Kaplan-Meier curves at 10 years and myeloablative selective HSCT at six years. We graded our certainty of evidence as moderate for non-myeloablative selective HSCT and myeloablative selective HSCT. Certainty of evidence was low for non-myeloablative non-selective HSCT. Event-free survival was improved compared to cyclophosphamide with non-myeloablative selective HSCT at 48 months (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.16 to 0.74; moderate-certainty evidence). There was no improvement with myeloablative selective HSCT at 54 months (HR 0.54 95% CI 0.23 to 1.27; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not report event-free survival. There was improvement in functional ability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI, scale from 0 to 3 with 3 being very severe functional impairment) with non-myeloablative selective HSCT after two years with a mean difference (MD) of -0.39 (95% CI -0.72 to -0.06; absolute treatment benefit (ATB) -13%, 95% CI -24% to -2%; relative percent change (RPC) -27%, 95% CI -50% to -4%; low-certainty evidence). Myeloablative selective HSCT demonstrated a risk ratio (RR) for improvement of 3.4 at 54 months (95% CI 1.5 to 7.6; ATB -37%, 95% CI -18% to -57%; RPC -243%, 95% CI -54% to -662%; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; low-certainty evidence). The non-myeloablative non-selective HSCT trial did not report HAQ-DI results. All transplant modalities showed improvement of modified Rodnan skin score (mRSS) (scale from 0 to 51 with the higher number being more severe skin thickness) favoring HSCT over cyclophosphamide. At two years, non-myeloablative selective HSCT showed an MD in mRSS of -11.1 (95% CI -14.9 to -7.3; ATB -22%, 95% CI -29% to -14%; RPC -43%, 95% CI -58% to -28%; moderate-certainty evidence). At 54 months, myeloablative selective HSCT at showed a greater improvement in skin scores than the cyclophosphamide group (RR 1.51, 95% CI 1.06 to 2.13; ATB -27%, 95% CI -6% to -47%; RPC -51%, 95% CI -6% to -113%; moderate-certainty evidence). The NNTB was 4 (95% CI 3 to 18). At one year, for non-myeloablative non-selective HSCT the MD was -16.00 (95% CI -26.5 to -5.5; ATB -31%, 95% CI -52% to -11%; RPC -84%, 95% CI -139% to -29%; low-certainty evidence). No studies reported data on pulmonary arterial hypertension. Adverse events In the non-myeloablative selective HSCT study, there were 51/79 serious adverse events with HSCT and 30/77 with cyclophosphamide (RR 1.7, 95% CI 1.2 to 2.3), with an absolute risk increase of 26% (95% CI 10% to 41%), and a relative percent increase of 66% (95% CI 20% to 129%). The number needed to treat for an additional harmful outcome was 4 (95% CI 3 to 11) (moderate-certainty evidence). In the myeloablative selective HSCT study, there were similar rates of serious adverse events between groups (25/34 with HSCT and 19/37 with cyclophosphamide; RR 1.43, 95% CI 0.99 to 2.08; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not clearly report serious adverse events.
AUTHORS' CONCLUSIONS
Non-myeloablative selective and myeloablative selective HSCT had moderate-certainty evidence for improvement in event-free survival, and skin thicknesscompared to cyclophosphamide. There is also low-certainty evidence that these modalities of HSCT improve physical function. However, non-myeloablative selective HSCT and myeloablative selective HSCT resulted in more serious adverse events than cyclophosphamide; highlighting the need for careful risk-benefit considerations for people considering these HSCTs. Evidence for the efficacy and adverse effects of non-myeloablative non-selective HSCT is limited at this time. Due to evidence provided from one study with high risk of bias, we have low-certainty evidence that non-myeloablative non-selective HSCT improves outcomes in skin scores, forced vital capacity, and safety. Two modalities of HSCT appeared to be a promising treatment option for SSc though there is a high risk of early treatment-related mortality and other adverse events. Additional research is needed to determine the effectiveness and adverse effects of non-myeloablative non-selective HSCT in the treatment of SSc. Also, more studies will be needed to determine how HSCT compares to other treatment options such as mycophenolate mofetil, as cyclophosphamide is no longer the first-line treatment for SSc. Finally, there is a need for a greater understanding of the role of HSCT for people with SSc with significant comorbidities or complications from SSc that were excluded from the trial criteria.
Topics: Adult; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Randomized Controlled Trials as Topic; Scleroderma, Systemic
PubMed: 35904231
DOI: 10.1002/14651858.CD011819.pub2