Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

Pidala, Joseph; Kim, J; Perkins, Janelle; Field, Teresa; Fernandez, Hugo F.; Perez, Lia; Ayala, Ernesto; Anasetti, Claudio

doi:10.1038/bmt.2009.252

Cited by 24 publications

(15 citation statements)

References 33 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reason for the high response rate observed in our patients compared to these studies is unclear, and it may be merely due to the small number of patients. A possible explanation is that the determinant dose of MMF given to each patient was higher than in previous studies, in which the dose of MMF used was typically in the range of 0.5–3 g/day in adult patients and 15–40 mg/kg/day in children or patients who weighed <50 kg . In the present study, higher starting doses of MMF (>40 mg/kg/day) were administered in seven patients.…”

Section: Discussioncontrasting

confidence: 55%

See 1 more Smart Citation

Mycophenolate mofetil for treatment of steroid‐refractory acute graft‐versus‐host disease after pediatric hematopoietic stem cell transplantation

Inagaki

Kodama

Fukano

et al. 2015

Pediatric Transplantation

View full text Add to dashboard Cite

A standard treatment is yet to be established for steroid-refractory acute aGVHD following HSCT. The effects of MMF have not been well studied in children with aGVHD. We evaluated the effectiveness of oral MMF in 14 children with steroid-refractory aGVHD (grade II in one patient, grade III to IV in 13 patients). The median initial dose of MMF was 40 mg/kg/day (range, 30-74) and was increased by 1.5-2 times if manifestations of GVHD did not improve. Within four wk of treatment, seven patients (50%) achieved CR, and four (29%) had a PR. Within eight wk, 11 patients (79%) achieved CR without using additional agents. Overall, 12 patients are alive and in remission with a median follow-up of 35 months (range, 14-86). The median maximum dose of MMF was 60 mg/kg/day (range, 34-107). No fatal toxicity was observed, including MMF-related infections. MMF appears to be highly effective for steroid-refractory aGVHD when used at a higher dose than has been described previously. Larger studies and pharmacokinetic analysis are required to evaluate its efficacy and toxicity and find the optimal dose of MMF in children.

show abstract

Section: Discussioncontrasting

confidence: 55%

“…MMF has already been studied as a salvage therapy for steroid‐refractory aGVHD – principally as a treatment for adult patients – and the CR rates were 15–60% . The reason for the high response rate observed in our patients compared to these studies is unclear, and it may be merely due to the small number of patients.…”

Section: Discussionmentioning

confidence: 82%

Mycophenolate mofetil for treatment of steroid‐refractory acute graft‐versus‐host disease after pediatric hematopoietic stem cell transplantation

Inagaki

Kodama

Fukano

et al. 2015

Pediatric Transplantation

View full text Add to dashboard Cite

show abstract

“…Furthermore, it is possible that MMF may delay or reduce engraftment in some patients, as myelosuppression is a known complication and has been previously reported. 25–27 Why a faster engraftment and a lower graft failure rate in the Valencia cohort did not translate into a lower NRM remains unexplained and is probably multifactorial.…”

Section: Discussionmentioning

confidence: 99%

Myeloablative Cord Blood Transplantation in Adults with Acute Leukemia: Comparison of Two Different Transplant Platforms

Sanz

Wagner

Sanz

et al. 2013

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

We compared the clinical outcomes of adults with acute leukemia that received single-unit umbilical cord blood transplantation (sUCBT) after conditioning with a busulfan/antithymocyte globulin (BU-ATG)-based regimen at University Hospital La Fe (n=102) or double-unit UCBT (dUCBT) after conditioning with a total body irradiation (TBI)-based regimen at the University of Minnesota (n=91). Non-relapse mortality, relapse and disease-free survival (DFS) were similar in the two groups. Multivariate analyses, showed more rapid neutrophil (HR 0.6; 95% CI 0.45 – 0.80; p = 0.0006) and platelet recovery (HR 0.59; 95% CI 0.43 – 0.83; p = 0.002) after the BU-ATG-based conditioning and sUCBT. While there was a lower risk of acute GVHD grade II–IV (HR 2.81; 95% CI 1.75 – 4.35; p < 0.001) after BU-ATG and sUCBT, the incidences of grade III–IV acute and chronic GVHD were similar between the two groups. Regarding disease-specific outcomes, DFS in both acute myeloid leukemia and acute lymphoblastic leukemia (ALL) patients were not significantly different; however, a significantly lower relapse rate was found in patients with ALL treated with TBI and dUCBT (HR 0.3; 95% CI 0.12 – 0.84; p = 0.02). In the context these specific treatment platforms our study demonstrates that sUCB and dUCBT offer similar outcomes.

show abstract

“…It is available in both oral and IV forms. There have been multiple published studies, both retrospective and prospective, using MMF in the treatment of steroid-refractory aGVHD [81,107]. In one study it was associated with responses in 9 out of 19 patients, but this did not translate into long-term overall survival [108].…”

Section: Mycophenolate Mofetil (Mmf)mentioning

confidence: 99%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

View full text Add to dashboard Cite

owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

show abstract

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

Cited by 24 publications

References 33 publications

Mycophenolate mofetil for treatment of steroid‐refractory acute graft‐versus‐host disease after pediatric hematopoietic stem cell transplantation

Mycophenolate mofetil for treatment of steroid‐refractory acute graft‐versus‐host disease after pediatric hematopoietic stem cell transplantation

Myeloablative Cord Blood Transplantation in Adults with Acute Leukemia: Comparison of Two Different Transplant Platforms

State-of-the-art acute and chronic GVHD treatment

Contact Info

Product

Resources

About