Efficacy of Mesenchymal Stem Cells for the Treatment of Steroid-Refractory aGVHD

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3913-3913 ◽  
Author(s):  
Kyoko Watakabe ◽  
Koichi Miyamura ◽  
Yukiyasu Ozawa ◽  
Masaya Okada ◽  
Takuya Yamashita ◽  
...  
Keyword(s):  
Hepatic Dysfunction ◽  
Complete Response ◽  
Efficacy And Safety ◽  
Hematopoietic Stem ◽  
Mixed Response ◽  
Underlying Malignancy ◽  
Graft Vs Host Disease ◽  
Multicenter Clinical Study ◽  
Steroid Refractory ◽  
Observation Period

Abstract Background: Steroid-refractory acute graft vs. host disease (SR-aGVHD) remains a significant complication of allogenic hematopoietic stem cell transplantation (allo-HSCT). In this phase II-III multicenter clinical study we evaluated the efficacy and safety of MSCs(JR-031; JCR Pharmaceuticals Co., Ltd., Japan) for SR-aGVHD. Method: 25 patients (age: 5-66 years, median 33years; male 15, female 10) who developed SR-aGVHD (grade III 22, grade IV 3) after allo-HSCT (Nov. 2011-Sept. 2012) were enrolled and given 8 biweekly infusions of 2x106 cells/kg of JR-031 for 4 weeks, with an additional 4 infusions weekly after 28 days in patients with partial response (PR). They were followed up to 24 weeks. Results: At 4 weeks after the first dose, 6 (24%) patients showed complete response (CR), 9 (36%) patients showed PR, 4 (16%) patients showed mixed response (MR) and 1(4%)patient showed no change (NC). During 24 weeks of observation period, 12 (48%) patients achieved durable CR (CR >=28days). As for response by organ, 80% (16/20) of GI, 66.7% (8/12) of skin and 66.7%(4/6) of liver GVHD completely responded (stage 0). 15 (60%) patients survived up to 24 weeks after the first dose.All patients experienced at least one adverse event(AE). Common AEs were leukopenia (12 patients), thrombopenia (9 patients), sepsis, anemia, TMA and hepatic dysfunction (6 patients). Among 10 death, causal relationship with JR-031 were not completely ruled out in 4 cases (TTP, pneumonia, sepsis and relapse of underlying malignancy), however there was no case in which the causality was strongly suggested. Conclusion: It was suggested that JR-031 is a safe and effective therapy in the treatment of patients with SR-aGVHD. Disclosures Miyamura: Novartis: Honoraria, Speakers Bureau.

Pentostatin in Steroid-Refractory Chronic Graft-Versus-Host Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1805-1805 ◽  
Author(s):  
Javier Bolanos-Meade ◽  
David Jacobsohn ◽  
Viki Anders ◽  
Megan Higman ◽  
Allen Chen ◽  
...  
Keyword(s):  
Partial Response ◽  
Graft Versus Host Disease ◽  
Calcineurin Inhibitor ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Main Concern ◽  
Host Disease ◽  
Graft Versus Host ◽  
Mixed Response ◽  
Steroid Refractory

Abstract Pentostatin, one of the purine nucleoside analogues, is known to decrease lymphocyte number and function. It has been successfully used to treat steroid refractory acute graft-versus-host disease (GVHD). We are currently investigating pentostatin for refractory chronic GVHD (cGVHD). Fifty-two patients were enrolled and 42 are assessable for response. All patients presented here failed at least two immunosuppressive regimens including steroids at a dose equivalent to at least 1 mg/kg/day prednisone for one month. The treatment protocol consists of giving pentostatin 4 mg/m2/dose IV every 2 weeks for 6 months. Patients with improving disease were permitted to continue pentostatin therapy at a 3 to 4 week interval. To reduce the risk of infection, steroids are tapered early in all patients and they received prophylactic antibiotics (antibiotics, fluconazole, sulfamethoxazole/trimethoprim and valcyclovir). At the end of 3 months, patients with stable or improving cGVHD are weaned off their other medications but maintained on a calcineurin inhibitor. Pentostatin is stopped at 6 months if complete response (CR) is achieved or continued if partial response (PR). Patients are followed for improvement in the skin/fascia, mouth, and liver. The severity of GVHD is scored for each system on a scale from 0 to 4. Complete response is resolution of symptoms (irreversible changes [such as long standing contractures] due to cGVHD were not required to improve to score a CR if all other changes improved); partial response is at least a 1 point improvement in this score system. Mixed response is improvement in 1 system but worsening in another. Fifty-two patients have received a median of 8.5 doses (range 1–34). Median age of the cohort is 40.5 years (range 5 to 67). Diagnoses include AML/MDS (6), ALL (7), hemoglobinopathy (2), aplastic anemia (3), CML (16), myelofibrosis (1), NHL (8), myeloma (4), paroxysmal nocturnal hemoglobinuria (3), CLL (1), and lymphohistiocytosis (1). Graft source included 20 patients: 6/6 sibling BMT; 10 patients: 6/6 sibling PBSCT; 10 patients: MUD BMT; 6 patients 5/6 MUD BMT; 2 patients: 6/6 MUD PBSCT; 1 patient 5/6 sibling BMT; 1 patient: 6/6 sibling BMT followed by DLI; 1 patient 5/6 BMT from a child; and 1 patient, unknown. Most patients were on calcineurin inhibitor, eleven on prednisone, seven on MMF, one on rapamycin, and one was receiving ECP at entry on the study. In the 42 assessable patients, 5 patients attained a CR, 16 a PR, 5 a mixed response (improvement in one organ with deterioration in another one), and 16 patients have progressed. The overall response rate is 50%. Therapy has been well-tolerated with infections being the main concern. Mucormycosis, pneumonia, disseminated fungal infection, fungal pneumonia, progressive disease were the causes of death of the 15 patients who have died and only infections could be related to the study drug. The results suggest that pentostatin has activity in the treatment of cGVHD and may be especially beneficial in children and adolescents as the 5 CR were in this group.

scholarly journals Liposomal Nystatin in Patients with Invasive Aspergillosis Refractory to or Intolerant of Amphotericin B

2004 ◽  
Vol 48 (12) ◽  
pp. 4808-4812 ◽  
Author(s):  
Fritz Offner ◽  
Vladimir Krcmery ◽  
Marc Boogaerts ◽  
Chantal Doyen ◽  
Dan Engelhard ◽  
...  
Keyword(s):  
Renal Function ◽  
Invasive Aspergillosis ◽  
Amphotericin B ◽  
Overall Response Rate ◽  
Response Rate ◽  
Hematological Malignancy ◽  
Study Drug ◽  
Complete Response ◽  
Hematopoietic Stem ◽  
Underlying Malignancy

ABSTRACT We assessed the activity and safety of liposomal nystatin, a broad-spectrum antifungal agent, for invasive aspergillosis in patients refractory to or intolerant of amphotericin B. Thirty-three patients were enrolled, received at least one dose of the study drug, and were evaluable for safety. Twenty-six patients had confirmed probable or definite aspergillosis and were fully eligible. Most patients had a hematological malignancy (53.8%) or hematopoietic stem cell transplantation (23.0%), were neutropenic (61.5%), and were refractory to previous amphotericin B (92.3%). The median duration of previous amphotericin B treatment was 16.5 days (range, 5 to 64 days). Aspergillosis was definite in 3 cases and probable in 23 cases. Liposomal nystatin was initiated at a dose of 4 mg/kg of body weight/day. Twenty-five patients were evaluable for response: a complete response was achieved for one patient, and a partial response was achieved for six. Thus, the overall response rate is 7 of 25 (28%; 95% confidence interval, 12 to 49%). Seventeen (68.0%) of the 25 evaluable patients died during therapy or within 1 month after the end of therapy. The primary cause of death was invasive aspergillosis for nine patients and underlying malignancy for eight patients. The most frequent side effects included chills, shivering, and fever, leading to discontinuation of therapy for two patients. Grade 1 decline in renal function was seen for 10 (30.3%) patients, and hypokalemia was seen for 13 (39.4%). We conclude that liposomal nystatin can be effective for salvage therapy of invasive aspergillosis. Infusion-related adverse events have been observed frequently.

scholarly journals Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Rui Zhang ◽  
Meng Zhou ◽  
Jiaqian Qi ◽  
Wenjing Miao ◽  
Ziyan Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Thrombotic Microangiopathy ◽  
Response Rate ◽  
Meta Analysis ◽  
Complete Response ◽  
Current Evidence ◽  
Efficacy And Safety ◽  
Impaired Liver Function ◽  
Hematopoietic Stem ◽  
Impaired Liver

BackgroundTransplant-associated thrombotic microangiopathy (TA-TMA) is a dangerous and life-threatening complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Eculizumab has been used in the treatment of TA-TMA, and several studies have confirmed the benefit of Eculizumab in patients with TA-TMA. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Eculizumab for TA-TMA.Materials and MethodsWe searched PubMed and Embase for studies on the efficacy and safety of Eculizumab in TA-TMA patients. Efficacy outcomes consisted of overall response rate (ORR), complete response rate (CRR), and survival rate at the last follow-up (SR). Safety outcomes were adverse events (AEs), including infection, sepsis, impaired liver function, infusion reactions, and death.ResultsA total of 116 patients from six studies were subjected to meta-analysis. The pooled estimates of ORR, CRR, and SR for TA-TMA patients were 71% (95% CI: 58–82%), 32% (95% CI: 11–56%), and 52% (95% CI: 40–65%), respectively. Only one patient presented with a severe rash, and infection was the most common AEs. The main causes of death were infection and GvHD.ConclusionCurrent evidence suggests that Eculizumab improves SR and ORR in patients with TA-TMA and that Eculizumab is well tolerated. However, the number of studies is limited, and the findings are based mainly on data from observational studies. Higher quality randomized controlled trials and more extensive prospective cohort studies are needed.

scholarly journals Efficacy and safety of intravesical fibrin glue instillation for management of patients with refractory hemorrhagic cystitis: 12-months results. A promising therapy for hemorrhagic cystitis

2021 ◽  
Vol 93 (2) ◽  
pp. 200-205
Author(s):  
Alessandra Cassani ◽  
Michele Marchioni ◽  
Francesco Silletta ◽  
Carlo D'orta ◽  
Giulia Primiceri ◽  
...  
Keyword(s):  
Clinical Response ◽  
Fibrin Glue ◽  
Hemorrhagic Cystitis ◽  
Bladder Wall ◽  
Onset Time ◽  
Complete Response ◽  
Efficacy And Safety ◽  
Marrow Graft ◽  
Hematopoietic Stem ◽  
Bladder Irrigation

Objectives: Fibrin glue (FG) endo-vesical application seems to be a promising therapy for hemorrhagic cystitis (HC). We aimed to evaluate efficacy and safety of FG instillation in patients with HC. Methods: Patients with HC not responsive to conventional treatments (bladder irrigation, catheterization, blood transfusions, hyperhydration and endoscopic coagulation) were treated with FG endo-vesical instillation (April 2017- December 2018). FG was prepared from 120 mL of patient blood with the Vivostat® system. After standard cystoscopy, bladder was insufflated with carbon dioxide (CO2) according to bladder compliance and autologous FG was applied to bladder wall and bleeding sites. Results: Ten patients included with grade 2 or higher HC secondary to bone marrow graft for hematological diseases (30%) or to actinic cystitis caused by prostate cancer radiotherapy (RT) (70%). The median HC onset time after RT was 4.8 (IQR 3.9- 6.3) years and 35 (IQR 27.5-62.5) days after hematopoietic stem cell transplantation (HSCT). Five patients had a complete response after one treatment, three patients had clinical response (grade < 2 hematuria, amelioration of symptoms), one of them required catheterization and bladder irrigation. One patient required a second instillation of FG achieving a clinical response. No adverse events related to the procedure were recorded, however one patient died for causes not related to the procedure. Median Interstitial Cystitis Symptoms Index was 13.0 (IQR 11.0-15.0) pre-operatively and 4.0 (IQR 2.0-5.0) post-operatively. Conclusions: Our study showed that, even in hematological patients, autologous FG instillation maybe a safe, repeatable and effective treatment modality in patients with refractory HC.

scholarly journals Comparisons Between Frontline Therapy and a Combination of Eltrombopag Plus Immunosuppression Therapy and Human Leukocyte Antigen-Haploidentical Hematopoietic Stem Cell Transplantation in Patients With Severe Aplastic Anemia: A Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuan Yang ◽  
Jiang Ji ◽  
Zengwei Tang ◽  
Bing Han
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Incidence Rate ◽  
Cell Transplantation ◽  
Efficacy And Safety ◽  
Hematopoietic Stem ◽  
Graft Vs Host Disease ◽  
Frontline Treatment

Background and Aims: This study aimed at comparing the efficacy and safety of eltrombopag (EPAG) plus immunosuppressive therapies (ISTs) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the frontline treatment for severe aplastic anemia (SAA) patients.Methods: Four electronic databases and Clinicaltrials.gov were comprehensively searched from January 2010 to August 2020. Studies that aimed at evaluating the efficacy and safety of EPAG+IST or haplo-HSCT in SAA patients were included. One-/2-year overall survival (OS), complete response (CR), and overall response rates (ORRs) were indirectly compared between EPAG+IST and haplo-HSCT.Results: A total of 447 patients involved in 10 cohort studies were found to be eligible for this study. A narrative synthesis was performed due to lack of data directly comparing the outcome of EPAG+IST and haplo-HSCT. Consistent with the analysis results in the whole population, subgroup analyses in the age-matched population showed that there was no significant difference in ORR between EPAG+IST and haplo-HSCT groups. However, the CR rate was lower in the EPAG+IST group when compared with the haplo-HSCT group. The incidence rate of clonal evolution/SAA relapse ranged at 8–14 and 19–31% in the EPAG+IST group but not reported in the haplo-HSCT group. The incidence rate for acute graft vs. host disease (aGVHD) and chronic graft vs. host disease (cGVHD) ranged at 52–57 and 12–67%, respectively, for the haplo-HSCT group. The main causes of deaths were infections in the EPAG+IST group, and GVHD and infections in the haplo-HSCT group.Conclusion: EPAG+IST has a comparable ORR and 1-/2-year OS but lower CR rate when indirectly compared with haplo-HSCT in the frontline treatment of patients with SAA. Patients treated with haplo-HSCT may exhibit a high incidence of GVHD, whereas patients treated with EPAG+IST may experience more relapses or clone evolution.

Pilot Study of Iodine-131–Metaiodobenzylguanidine in Combination With Myeloablative Chemotherapy and Autologous Stem-Cell Support for the Treatment of Neuroblastoma

2002 ◽  
Vol 20 (8) ◽  
pp. 2142-2149 ◽  
Author(s):  
Gregory A. Yanik ◽  
John E. Levine ◽  
Katherine K. Matthay ◽  
James C. Sisson ◽  
Barry L. Shulkin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pilot Study ◽  
Neuroblastoma Cells ◽  
Complete Response ◽  
Novel Therapy ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Stem Cell Rescue ◽  
Myeloablative Chemotherapy ◽  
Iodine 131

PURPOSE: The survival for children with relapsed or metastatic neuroblastoma remains poor. More effective regimens with acceptable toxicity are required to improve prognosis. Iodine-131–metaiodobenzylguanidine (131I-MIBG) selectively targets radiation to catecholamine-producing cells, including neuroblastoma cells. A pilot study was performed to examine the feasibility of a novel regimen combining 131I-MIBG and myeloablative chemotherapy with autologous stem-cell rescue. PATIENTS AND METHODS: Twelve patients with neuroblastoma were treated after relapse (five patients) or after induction therapy (seven patients). Eight patients had metastatic and four had localized disease at the time of therapy. All patients received 131I-MIBG 12 mCi/kg on day −21, followed by carboplatin (1,500 mg/m2), etoposide (800 mg/m2), and melphalan (210 mg/m2) administered from day −7 to day −4. Autologous peripheral-blood stem cells or bone marrow were infused on day 0. Engraftment, toxicity, and response rates were evaluated. RESULTS: The 131I-MIBG infusion and myeloablative chemotherapy were both well tolerated. Grade 2 to 3 oral mucositis was the predominant nonhematopoietic toxicity, occurring in all patients. The median times to neutrophil (≥ 0.5 × 103/μL) and platelet (≥ 20 × 103/μL) engraftment were 10 and 28 days, respectively. For the eight patients treated with metastatic disease, three achieved complete response and two had partial responses by day 100 after transplantation. CONCLUSION: Treatment with 131I-MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell rescue is feasible with acceptable toxicity. Future study is warranted to examine the efficacy of this novel therapy.

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