mycophenolic-acid and Bone-Marrow-Diseases

Various immunosuppressive regimens have been developed for the treatment of lupus nephritis (LN). This study aimed to compare the efficacy and safety of immunosuppressive regimens in adults with LN.. We systematically searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases, including conference proceedings, trial registries, and reference lists, from inception until July 10, 2022. The effects of treatment were compared and ranked using the surface under the cumulative ranking curve (SUCRA). The primary endpoint was total remission. The secondary endpoints were complete remission, systemic lupus erythematosus disease activity index (SLEDAI), relapse, all-cause mortality, end-stage renal disease (ESRD), infection, herpes zoster, ovarian failure, myelosuppression, and cancer.. Sixty-two trials reported in 172 studies involving 6,936 patients were included in the network meta-analysis. The combination of tacrolimus (TAC), mycophenolate mofetil (MMF), and glucocorticoid (GC) provided the best result for the total remission rate (SUCRA, 86.63%) and SLEDAI (SUCRA, 91.00%), while the combination of voclosporin (VCS) , MMF and GC gave the best improvement in the complete remission rate (SUCRA, 90.71%). The combination of cyclophosphamide (CYC), MMF and GC was associated with the lowest risk of relapse (SUCRA, 85.57%) and cancer (SUCRA, 85.14%), while the combination of obinutuzumab (OTB), MMF and GC was associated with the lowest risk of all-cause mortality (SUCRA, 84.07%). Rituximab (RTX) plus MMF plus GC was associated with the lowest risk of ESRD (SUCRA, 83.11%), while the risk of infection was lowest in patients treated with azathioprine (AZA) plus CYC plus GC (SUCRA, 68.59%). TAC plus GC was associated with the lowest risk of herpes zoster (SUCRA, 87.67%) and ovarian failure (SUCRA, 73.60%). Cyclosporine (CsA) plus GC was associated with the lowest risk of myelosuppression (SUCRA, 79.50%), while AZA plus GC was associated with the highest risk of myelosuppression (SUCRA, 16.25%).. This study showed that a combination of TAC, MMF and GC was the best regimen for improving the total remission rate. The optimal regimen for specific outcomes should be highlighted for high-risk patients.

Topics: Adult; Azathioprine; Bone Marrow Diseases; Cyclophosphamide; Glucocorticoids; Herpes Zoster; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Lupus Nephritis; Mycophenolic Acid; Neoplasms; Network Meta-Analysis; Recurrence; Tacrolimus; Treatment Outcome

Acquired pure megakaryocytic aplasia (APMA) is a rare disorder in the field of hematological diseases. We report the case of a patient with APMA treated with mycophenolate mofetil and review the literature associated with this. Until today, very few cases of APMA have been reported and the disease etiology still seems to be unclear. There have been no reported cases of treatment of APMA treated with mycophenolate mofetil.

Topics: Aged; Bone Marrow Diseases; Humans; Male; Megakaryocytes; Mycophenolic Acid; Platelet Count

The risk of graft-rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide-based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA-alloimmunized. Fifty-six patients with BMFS underwent fludarabine-based reduced-intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine, and equine antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A alone or in combination with either mycophenolate mofetil or methotrexate. To reduce the risk of graft-rejection/failure, unmanipulated G-CSF mobilized PBPCs obtained from an HLA-identical or single HLA-antigen mismatched relative were transplanted rather than donor bone marrow. Despite a high prevalence of pretransplant HLA-alloimmunization (41%) and a heavy prior transfusion burden, graft-failure did not occur with all patients having sustained donor lympho-hematopoietic engraftment. The cumulative incidence of grade II-IV acute-GVHD and chronic-GVHD was 51.8% and 72%, respectively; with 87.1% surviving at a median follow-up of 4.5 years. A multivariate analysis showed pretransplant alloimmunization and rapid donor T-cell engraftment (≥95% donor by day 30) were both significantly (P < 0.05) associated with the development of chronic-GVHD (adjusted HR 2.13 and 2.99, respectively). These data show fludarabine-based PBPC transplantation overcomes the risk of graft-failure in patients with BMFS, although rapid donor T-cell engraftment associated with this approach appears to increase the risk of chronic-GVHD. (Clinicaltrials.gov identifier: NCT00003838).

Topics: Adult; Aged; Anemia, Aplastic; Antilymphocyte Serum; Antineoplastic Agents; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Chronic Disease; Cyclosporine; Female; Graft Rejection; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hemoglobinuria, Paroxysmal; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Risk Factors; Salvage Therapy; T-Lymphocytes; Time Factors; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Young Adult

Post-transplantation cyclophosphamide (PTCy) demonstrated effectiveness to prevent GVHD after haploidentical hematopoietic cell transplantation (HCT). Reducing toxicities with a maximized efficacy is still challenging in HCT. In this retrospective study, we analyzed the safety and efficacy of transplantation from a 1-antigen HLA-mismatched unrelated donor (9/10 MMUD) in 80 patients with hematological disorders between 2010 and 2018; 22 patients received PTCy with a reduced dose of 40 mg/kg, cyclosporine A, and mycophenolate mofetil (MMF); 58 patients received anti-thymocyte globulin (ATG), cyclosporine A, and either methotrexate or MMF for GVHD prophylaxis. Cumulative incidence (CI) of acute GVHD grades II-IV in the PTCy group was significantly lower (15% vs. 50%, p = 0.006); however, CI of chronic GVHD was (not significantly) lower in the PTCy group (26% vs. 35%, p = 0.137). One-year OS was significantly longer (p = 0.008) in the PTCy group with a similar 1-year PFS (p = 0.114) in both groups. Rates of 1-year relapse and non-relapse mortality were similar. Median time to neutrophil engraftment was comparable in both GVHD prophylaxis groups (14 days vs. 16 days, respectively, p = 0.107). Our results show that a lower dose of PTCy-based prophylaxis is an effective and safe strategy to prevent acute GVHD in HCT with 9/10 MMUD compared to ATG.

Topics: Adult; Aged; Anemia, Aplastic; Antilymphocyte Serum; Bone Marrow Diseases; Bone Marrow Failure Disorders; Cyclophosphamide; Cyclosporine; Drug Evaluation; Female; Graft Survival; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hemoglobinuria, Paroxysmal; Histocompatibility; HLA Antigens; Humans; Immunosuppressive Agents; Incidence; Male; Middle Aged; Mycophenolic Acid; Neoplasms; Retrospective Studies; T-Lymphocytes; Tissue Donors

Sarcoidosis is a multisystem granulomatous disease that may involve the bone marrow, with resultant fever, anemia, and leukopenia. Although generally effective in treating the clinical manifestations of bone marrow sarcoidosis, systemic corticosteroids are not warranted for long-term therapy because of their well-known adverse effects. Therefore, alternative corticosteroid-sparing therapeutic regimens are desired.. A 41-year-old man sought treatment for cutaneous and bone marrow sarcoidosis resulting in fatigue, anemia, and leukopenia refractory to conventional therapies and mycophenolate mofetil. We initiated combination immunosuppressive therapy with methotrexate sodium and mycophenolate mofetil, which resulted in a safe and prolonged quiescence of cutaneous disease and resolution of anemia and leukopenia throughout a 34-month follow-up period.. We present this case to highlight the growing body of evidence supporting combination immunosuppressive therapy to treat refractory sarcoidosis. In our patient, sarcoidal bone marrow involvement responded dramatically to a combined regimen of methotrexate and mycophenolate mofetil with no significant adverse effects, despite previously having been refractory to conventional agents and mycophenolate mofetil alone. This report provides evidence that combination immunosuppressive therapy is a potential treatment of refractory bone marrow sarcoidosis and highlights important issues about combined immunosuppressive therapy.

Topics: Adult; Anemia; Bone Marrow Diseases; Drug Therapy, Combination; Humans; Immunosuppressive Agents; Leukopenia; Male; Methotrexate; Mycophenolic Acid; Sarcoidosis; Skin Diseases

Gelatinous transformation of the bone marrow is a rare disease characterised by a focal marrow hypoplasia, fat atrophy and accumulation of extracellular mucopolysaccharides abundant in hyaluronic acid, which is often associated with extreme malnutrition and weight loss. There are only two reports describing its association with systemic lupus erythematosus (SLE). One described underlying diseases in 155 cases of gelatinous transformation of the bone marrow and found one case with clinical diagnosis of SLE, but no clinical details were provided. The other described three SLE patients with gelatinous transformation of the bone marrow; however, two of these were cachectic and one was diagnosed with concomitant tuberculosis. We describe one active SLE patient without other comorbidities whose pancytopaenia was histologically confirmed as gelatinous transformation. The combination of high-dose steroid, intravenous immunoglobulin and mycophenolate mofetil improved the peripheral blood cytopaenia and reversed the bone marrow abnormalities.

Topics: Anti-Inflammatory Agents; Biopsy; Bone Marrow; Bone Marrow Diseases; Female; Glycosaminoglycans; Humans; Hyaluronic Acid; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Methylprednisolone; Middle Aged; Mycophenolic Acid