mycophenolic-acid and Myelodysplastic-Syndromes

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P < .001) and grade III to IV acute GVHD (RR, 1.93; P = .006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P = .008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.

Topics: Adult; Aged; Allografts; Calcineurin Inhibitors; Disease-Free Survival; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Retrospective Studies; Siblings; Survival Rate; Tacrolimus; Transplantation Conditioning

The combination of cytoreductive chemotherapy with reduced-intensity conditioning (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine-based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT) for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27 patients underwent allogeneic SCT after treatment with clofarabine and ara-C for 5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of this regimen mainly affected liver and skin and were all reversible. Seven patients relapsed within a median time of 5.7 months. The overall survival (OS) and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC allogeneic SCT was well tolerated and showed good antileukemic efficacy even in patients with high-risk AML or MDS, with engraftment and GvHD-incidence comparable to other RIC regimens.

Topics: Adenine Nucleotides; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleosides; Clofarabine; Cyclosporine; Cytarabine; Disease-Free Survival; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Retrospective Studies; Stem Cell Transplantation; Survival Rate; Transplantation Conditioning; Transplantation, Homologous

In the current study, we have analyzed the efficacy of cyclosporine A (CSA) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis in the fludarabine plus melphalan or busulfan reduced intensity regimen (RIC) setting in a series of 44 patients receiving allogeneic transplantation from an unrelated donor. Only 23% were in the first complete remission at the time of transplant. Cumulative incidence of grades II-IV and III-IV acute GVHD (aGVHD) was 53% and 23%, respectively. Fifty-six percent had equal to or greater than grade 2 gut involvement. Cumulative incidence of overall and extensive chronic GVHD (cGVHD) was 93% and 63%, respectively. Ninety-two percent of patients who were evaluable +100 days after transplant were in complete remission. Relapse rate was 25% at 2 years. Event free (EFS) and overall survival (OS) at 2 years were 52%. Pharmacokinetic assays of mycophenolic acid (MPA) showed a therapeutic area under the curve (AUC) at the dosage of 3 g daily, although a large inter- and intraindividual variations of MPA plasma levels were found. In conclusion, the combination of CSA plus MMF in the fludarabine plus melphalan or busulfan RIC setting is feasible. Regarding GVHD, this combination allowed to control aGVHD but lead to a high incidence of cGVHD, so that newer strategies are required, especially in trying to decrease gastrointestinal involvement.

Topics: Adolescent; Adult; Antineoplastic Agents; Bone Marrow Transplantation; Busulfan; Combined Modality Therapy; Cyclosporine; Drug Therapy, Combination; Female; Graft vs Host Disease; Hematologic Neoplasms; Humans; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Mycophenolic Acid; Myeloablative Agonists; Myelodysplastic Syndromes; Peripheral Blood Stem Cell Transplantation; Survival Analysis; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

Severe aplastic anaemia (SAA) can be successfully treated with immunosuppressive therapies or haematopoietic stem cell transplantation (HSCT). Response rates with horse anti-thymocyte globulin (h-ATG) plus ciclosporin (CsA) are about 60-70%, and robust responders have an excellent long-term survival. We introduced a third immunosuppressive agent to standard h-ATG/CsA, mycophenolate mofetil (MMF), in an attempt to improve the response rate and survival, and to decrease the relapse rate and clonal evolution to myelodysplasia. A total of 104 consecutive patients with SAA were treated with h-ATG/CsA/MMF between May 1999 and June 2003 at the National Institutes of Health Clinical Center. The overall response rate at 6 months was 62%, with 24 (37% of responders) patients relapsing at a median of 389 d from ATG. Nine patients showed evidence of clonal evolution following ATG. After a median follow up of 42 months, the median survival among responders was not reached and among non-responders was 58 months. Over half of the relapses occurred during MMF administration. Despite a strong theoretical rationale for its use, MMF did not result in the improvement of response or relapse rates when compared with historical standard h-ATG/CsA.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Antilymphocyte Serum; Child; Child, Preschool; Combined Modality Therapy; Cyclosporine; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Recurrence; Survival Analysis; Treatment Outcome

Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT.. We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically.. Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level <400 mg/dl was not associated with the occurrence of infection between the test studied and the next one (aOR 1.33 [0.84-2.15], P = .24). The gamma globulin level was not predictive of bacterial or fungal infections (AUC 0.54 [95%CI: 0.47-0.61]) nor of viral reactivations (AUC 0.51 [95%CI: 0.43-0.60]).. This confirmed that the humoral deficiency is a minor part of the immune deficiency in the 100 days post-transplant. This questions the relevance of the indications of immunoglobulin substitution during this period.

Topics: Aged; Bacterial Infections; Cyclosporine; Female; gamma-Globulins; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Leukemia; Lymphoma; Male; Middle Aged; Mycophenolic Acid; Mycoses; Myeloablative Agonists; Myelodysplastic Syndromes; Opportunistic Infections; Prognosis; ROC Curve; Transplantation Conditioning; Transplantation, Homologous; Virus Activation

Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in graft-versus-host disease prophylaxis because of its inhibitory function on T cells and B cells. However, the effect of MMF on natural killer cell reconstitution after allogenic hematological transplantation is largely unknown. The present study examined the effects of different MMF administration durations after haploidentical allo-HSCT on NK cell reconstitution. Ninety patients were enrolled in this study and defined into two groups in term of MMF duration. We found that MMF patients in the long-term MMF group were associated with a poor reconstitution of NK cells and a significantly lower cytotoxicity from day 30 to day 180 post-transplantation. Especially, the long-term MMF group inhibits reconstitution of NKp30 NK subsets, which correlated with higher risk of EBV viremia. Multivariate analysis showed that a better reconstitution of NKp30 cells was associated with lower EBV viremia (HR0.957, p = .04). In vitro experiments demonstrated that the active metabolite of MMF, mycophenolic acid (MPA), inhibited the proliferation and cytotoxicity of NK cells from healthy donors or patients at day 30 post-transplantation. In summary, our findings demonstrated that long-term MMF administration delayed the quality and quantity of NK cells, especially NKp30 subpopulations, which was associated with decreased EBV viremia post allogeneic HSCT.

Topics: Adolescent; Adult; Duration of Therapy; Epstein-Barr Virus Infections; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; Humans; Immune Reconstitution; Immunosuppressive Agents; Killer Cells, Natural; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Natural Cytotoxicity Triggering Receptor 3; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proportional Hazards Models; Transplantation, Homologous; Viremia; Young Adult

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukemia, B-Cell; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Neoplasms, Second Primary; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Sirolimus

Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease (AID) and an emerging clinical phenomenon.. To query the association of cytotoxic, anti-inflammatory, and immunomodulating agents to treat patients with AID with the risk for developing myeloid neoplasm.. This retrospective case-control study and medical record review included 40 011 patients with an International Classification of Diseases, Ninth Revision, coded diagnosis of primary AID who were seen at 2 centers from January 1, 2004, to December 31, 2014; of these, 311 patients had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met strict inclusion criteria. A case-control match was performed at a 2:1 ratio.. Odds ratio (OR) assessment for AID-directed therapies.. Among the 86 patients who met inclusion criteria (49 men [57%]; 37 women [43%]; mean [SD] age, 72.3 [15.6] years), 55 (64.0%) had MDS, 21 (24.4%) had de novo AML, and 10 (11.6%) had AML and a history of MDS. Rheumatoid arthritis (23 [26.7%]), psoriasis (18 [20.9%]), and systemic lupus erythematosus (12 [14.0%]) were the most common autoimmune profiles. Median time from onset of AID to diagnosis of myeloid neoplasm was 8 (interquartile range, 4-15) years. A total of 57 of 86 cases (66.3%) received a cytotoxic or an immunomodulating agent. In the comparison group of 172 controls (98 men [57.0%]; 74 women [43.0%]; mean [SD] age, 72.7 [13.8] years), 105 (61.0%) received either agent (P = .50). Azathioprine sodium use was observed more frequently in cases (odds ratio [OR], 7.05; 95% CI, 2.35- 21.13; P < .001). Notable but insignificant case cohort use among cytotoxic agents was found for exposure to cyclophosphamide (OR, 3.58; 95% CI, 0.91-14.11) followed by mitoxantrone hydrochloride (OR, 2.73; 95% CI, 0.23-33.0). Methotrexate sodium (OR, 0.60; 95% CI, 0.29-1.22), mercaptopurine (OR, 0.62; 95% CI, 0.15-2.53), and mycophenolate mofetil hydrochloride (OR, 0.66; 95% CI, 0.21-2.03) had favorable ORs that were not statistically significant. No significant association between a specific length of time of exposure to an agent and the drug's category was observed.. In a large population with primary AID, azathioprine exposure was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category. No association was found for anti-tumor necrosis factor agents. Finally, no timeline was found for the association of drug exposure with the incidence in development of myeloid neoplasm.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoimmune Diseases; Azathioprine; Case-Control Studies; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Incidence; Leukemia, Myeloid, Acute; Lupus Erythematosus, Systemic; Male; Mercaptopurine; Methotrexate; Middle Aged; Mitoxantrone; Mycophenolic Acid; Myelodysplastic Syndromes; Odds Ratio; Psoriasis; Retrospective Studies; Risk Factors; United States

There have been few reports on allogeneic stem cell transplantation in patients who have previously undergone solid organ transplantation. The clinical course of such patients is not yet well recognized. Therefore, appropriate immunosuppressive prophylaxis for the rejection of a solid organ graft or for graft-versus-host disease has not yet been established. We present the case of a successful allogeneic stem cell transplantation in a patient who relapsed after a first allogeneic stem cell transplantation for myelodysplastic syndrome and who had previously undergone renal transplantation. The prophylaxis in this case for graft-versus-host disease and rejection of the transplanted kidney was mycophenolate mofetil and tacrolimus. No hyperacute rejection of the transplanted kidney was observed. However, the patient's renal function deteriorated after the cessation of the mycophenolate mofetil and the reduction of the tacrolimus. This deterioration seemed to be due to rejection with humoral immunity of donor lymphocytes, and we were able to control it by resuming the mycophenolate mofetil and local graft irradiation.

Topics: Drug Therapy, Combination; Female; Graft Rejection; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukemia, Myeloid, Acute; Male; Middle Aged; Mothers; Mycophenolic Acid; Myelodysplastic Syndromes; Recurrence; Retreatment; Siblings; Tacrolimus; Tissue Donors; Transplant Recipients; Transplantation, Homologous

Topics: Acute Kidney Injury; Adult; Blood Component Transfusion; Bone Marrow; Cell Lineage; Combined Modality Therapy; Darbepoetin alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematuria; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Lymphohistiocytosis, Hemophagocytic; Male; Mycophenolic Acid; Myelodysplastic Syndromes; Pancytopenia; Pericarditis; Prednisone; Proteinuria; Recombinant Proteins

Pseudo-Pelger-Huët anomaly (PPHA) has been documented in association with transplant medications and other drugs. This iatrogenic neutrophilic dysplasia is reversible with cessation or adjustment of medications but is frequently confused with myelodysplastic syndrome (MDS) based on the conventional concept that PPHA is a marker for dysplasia. We investigated the clinicopathologic features in iatrogenic PPHA and compared them with MDS-related PPHA. The 13 cases studied included 5 bone marrow/stem cell transplantations, 3 solid organ transplantations, 1 autoimmune disease, 3 chronic lymphocytic leukemias, and 1 breast carcinoma. For 12 cases, there was follow-up evaluation, and all demonstrated at least transient normalization of neutrophilic segmentation. All 9 cases of MDS demonstrated at least 2 of the following pathologic abnormalities on bone marrow biopsy: hypercellularity (8/9), morphologic dysplasia (8/9), clonal cytogenetic abnormality (7/9), and increased blasts (3/9), whereas these abnormalities were typically absent in iatrogenic PPHA. Iatrogenic PPHA displayed a higher proportion of circulating PPHA cells than in MDS (mean, 47.4%; SD, 31.6% vs mean, 12.3%; SD, 9.8; P < .01). A diagnostic algorithm is proposed in which isolated PPHA is indicative of transient or benign PPHA unless proven otherwise.

Topics: Adult; Aged; Bone Marrow; Bone Marrow Transplantation; Chromosome Aberrations; Female; Humans; Iatrogenic Disease; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Neutrophils; Pelger-Huet Anomaly; Stem Cell Transplantation; Tacrolimus

Topics: Drug Resistance; Erythropoietin; Humans; Immunosuppressive Agents; Mycophenolic Acid; Myelodysplastic Syndromes; Recombinant Proteins

We describe herein the clinical courses and outcomes of 26 patients who received oral mycophenolate mofetil (MMF) for the treatment of steroid-resistant refractory or steroid-dependent acute or chronic graft-versus-host disease (GVHD) in a single institution. In most cases, 1,500 mg/day of MMF is a median dose (range 500-3,000 mg/day) and administered for 116.5 days (range 9-584 days) along with calcineurin inhibitors and steroids. Although 20 patients (77%) showed rapid improvement of GVHD symptoms, of 15 patients, 13 (87%) showed acute GVHD; of 11 patients, 7 (64%) showed chronic GVHD; most patients (54%) experienced infection during MMF administration, including 5 cases with life-threatening infection. Positive cytomegalovirus (CMV) antigenemia was also observed in 19 patients (73%), but no patients developed CMV infection. Within the median follow-up of 12.5 months (range 0.5-67 months), 10 patients (39%) died. This small study demonstrates that MMF offers an alternative tool for rescuing steroid-refractory or steroid-dependent GVHD, but increases the risk of developing life-threatening infection.

Topics: Acute Disease; Adult; Anemia, Aplastic; Chronic Disease; Female; Graft vs Host Disease; Humans; Immunocompromised Host; Immunosuppressive Agents; Infections; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Risk Factors; Stem Cell Transplantation; Survival Analysis; Transplantation, Homologous; Young Adult

We report a patient who developed multiple serositis during chronic graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation from a non-inherited maternal antigen (NIMA) -complementary sibling donor. The patient was a 9-year-old boy with myelodysplastic syndrome, who urgently underwent bone marrow transplantation from his NIMA-complementary HLA two-locus-mismatched sister following graft failure of cord blood transplantation. Engraftment was successfully confirmed and no acute GVHD developed. After withdrawal of tacrolimus to prevent recurrent viral infection, he developed pleural effusion, ascites and edema approximately 6 months after transplantation. His clinical symptoms were resolved by methylprednisolone pulse therapy, but he subsequently progressed to develop pericardial effusion, pneumothorax and truncal panniculitis. Pleural and pericardial effusion contained numerous lymphocytes, which gradually subsided with continuous drainage. His symptoms were thereafter controlled by the addition of mycophenolate mofetil (MMF) administration, and his current performance status is almost perfect by the administration of prednisolone (5 mg/day) and MMF at 6 years after transplantation. Although multiple serositis associated with GVHD is known to have a poor prognosis, the multiple symptoms of this patient improved gradually, probably owing to a lack of acute GVHD and the effect of MMF.

Topics: Adolescent; Bone Marrow Transplantation; Child; Chronic Disease; Drainage; Female; Graft vs Host Disease; Histocompatibility; HLA Antigens; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Myelodysplastic Syndromes; Serositis; Siblings; Tissue Donors; Treatment Outcome

To prevent acute graft-versus-host disease (GVHD), mycophenolate mofetil (MMF) combined with calcineurin inhibitors have been used in allogeneic hematopoietic stem cell transplantation (allo-SCT). Previous studies commonly utilize MMF treatment until day 30 after allo-SCT. However, the feasibility of continuous administration after day 30 has not been well evaluated. We retrospectively assessed the safety and efficacy of extended drug administration. Twenty-five patients ceased MMF at day 30 (group A); whereas, 16 patients (group B) received extended regimens depending on individual risk factors for GVHD. No severe adverse events were observed in either group. Although the cumulative incidence (CI) of grade I to IV GVHD at day 100 was comparable between the 2 groups, the CI of grade II to IV GVHD was less among group B (12.5%) compared with group A (42.3%). Extended MMF administration may be safe and beneficial as preemptive therapy to reduce the development of moderate-to-severe acute GVHD.

Topics: Adult; Aged; Cyclosporine; Drug Administration Schedule; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leukemia; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Safety; Tacrolimus; Time Factors; Transplantation, Homologous; Young Adult

A 32-yr-old male diagnosed with myelodysplastic syndrome underwent an unmanipulated, unrelated, HLA matched, peripheral blood stem cell transplantation. The patient and donor were both blood type O, CcDEe. Twelve weeks post-transplantation, he developed acute autoimmune hemolytic anemia (AIHA). He was transfused multiple times with washed O red cells. High-dose steroid therapy was initiated and he underwent splenectomy; however, AIHA was refractory to therapy. The patient was further treated with combined treatment modalities including immunosuppressive therapy with mycophenolate mofetil and cyclosporine and three cycles of plasma exchange, and AIHA responded to treatment. This is the third case of AIHA complicating hematopoietic stem cell transplantation reported in Korea. Since AIHA is relatively common after hematopoietic stem cell transplantation, accurate and timely diagnosis of the disease and treatment strategies with multiple modalities are necessary.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Combined Modality Therapy; Cyclosporine; Hematopoietic Stem Cell Transplantation; Humans; Male; Mycophenolic Acid; Myelodysplastic Syndromes; Plasma Exchange

The combination of Cyclosporin A (CSA) and Methotrexate (MTX) is considered to be the standard regimen for the prevention of graft-versus-host disease (GVHD) after stem cell transplantation (SCT) from HLA-identical siblings. Mycophenolate Mofetil (MMF) has been widely used for GVHD prophylaxis after nonmyeloablative SCT, but experience following myeloablative therapy is still limited. We retrospectively compared CSA/MTX and CSA/MMF in 93 patients (median age 35 years, range 17-59 years, male subjects 48, female subjects 45) with acute myeloid leukemia (n=33), myelodysplastic syndrome (MDS) (n=3), acute lymphoblastic leukemia (ALL) (n=20) or chronic myeloid leukemia (n=37) who received CSA/MMF (n=26) or CSA/MTX (n=67) as GVHD prophylaxis following high-dose therapy and allogeneic SCT from HLA-identical siblings. No statistically significant differences were found in overall survival, relapse rate, treatment-related mortality and acute or chronic GVHD. Time to myeloid recovery was significantly shorter in patients who received CSA/MMF. We conclude that the combination of CSA/MMF appears equivalent to CSA/MTX for GVHD prophylaxis in patients receiving conventional-intensity SCT from HLA-identical siblings.

Topics: Adolescent; Adult; Cyclosporine; Female; Graft vs Host Disease; Histocompatibility; Histocompatibility Testing; HLA Antigens; Humans; Immunosuppressive Agents; Leukemia; Living Donors; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Recurrence; Retrospective Studies; Siblings; Stem Cell Transplantation; Time Factors; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome

Autoimmune hemolytic anemia (AIHA) rarely occurs in myelodysplastic syndrome (MDS). A 36-year-old Asian female was diagnosed with MDS (refractory cytopenia with multilineage dysplasia, RCMD) and complicated by AIHA 7 months later. Secondary myelofibrosis developed at the same time. Steroid therapy was ineffective and cyclosporin A (CsA) was discontinued due to its neurotoxicity with the development of leukoencephalopathy. However, the patient achieved a good hematological response after the use of mycophenolate mofetil (MMF, CellCept) with a dose of 1 g/day and prednisolone (15 mg/day). Prednisolone was tapered off over the next 3 weeks. The patient did not require any blood support 4 weeks after the use of MMF and has been hematologically stable for 4 months. To our knowledge, this is the first report of using MMF in treating MDS complicated by AIHA. MMF might be considered as a salvage therapy for patients with refractory anemia complicated by AIHA.

Topics: Adult; Anemia, Hemolytic, Autoimmune; Anemia, Refractory; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Mycophenolic Acid; Myelodysplastic Syndromes; Prednisolone; Primary Myelofibrosis; Remission Induction; Salvage Therapy

Topics: Adult; Bone Marrow Transplantation; Child; Chromatin; Granulocytes; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Myelodysplastic Syndromes

Inosine 5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We investigated the ability of mycophenolate mofetil, a prodrug of mycophenolic acid, to induce differentiation in HL-60 and U937 leukemic cells as well as in fresh leukemia cells from patients with non-lymphocytic leukemia. Treatment with mycophenolate mofetil reduced the intracellular guanosine 5'-triphosphate (GTP) levels and induced morphologic and functional differentiation in HL-60 and U937 cells dose-dependently. HL-60 and U937 cells developed macrophage-like cytoplasm as well as the expression of CD11b and CD14 antigens and the ability to oxidize nitroblue tetrazorium (NBT). These changes became evident when the intracellular GTP levels decreased to approximately 20-30% of the untreated control level and were abrogated by the addition of guanosine. In the fresh leukemic cells, differentiation induction was shown in the cells derived from seven of 13 patients. The fresh leukemia cells responding to mycophenolate mofetil revealed significant higher positivity to CD11b, CD14, and NBT before treatment and significantly reduced intracellular GTP levels after treatment compared to the non-responding cells. These findings suggest that mycophenolate mofetil induces differentiation in HL-60 and U937 cells and some fresh leukemia cells with moderate tendency to maturation, by causing a decrease in the intracellular GTP levels. Mycophenolate mofetil could be a promising differentiation inducer in vivo.

Topics: Adult; Aged; Antineoplastic Agents; Cell Differentiation; Female; HL-60 Cells; Humans; Leukemia, Myeloid; Male; Middle Aged; Mycophenolic Acid; Myelodysplastic Syndromes; Tumor Cells, Cultured; U937 Cells