mycophenolic-acid and Leukemia--Myelomonocytic--Chronic

Infliximab-daclizumab was used to treat acute and chronic liver and gut graft-versus-host disease (GVHD) in two children after standard immunosuppressive therapy failed. Infliximab (10 mg/kg weekly, 4 doses) and daclizumab (1 mg/kg, days 1, 4, 8, 15, and 22) were given over 1 month. In case 1, grade 2 chronic GVHD of the liver developed 1 year after transplantation and failed to improve with tacrolimus, mycophenolate mofetil, and prednisone. In case 2, corticosteroid-unresponsive grade 3 acute liver and gut GVHD developed on day +37. In both patients, GVHD responded to the infliximab-daclizumab regimen without toxicity and immunosuppressive therapy was discontinued.

Topics: Acute Disease; Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Child; Chronic Disease; Combined Modality Therapy; Daclizumab; Drug Resistance; Drug Therapy, Combination; Graft vs Host Disease; Humans; Immunoglobulin G; Immunosuppressive Agents; Infliximab; Interleukin-2 Receptor alpha Subunit; Intestinal Mucosa; Leukemia, Myelomonocytic, Chronic; Liver; Mycophenolic Acid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Recurrence; Remission Induction; Reoperation; Tacrolimus; Transplantation, Homologous; Tumor Necrosis Factor-alpha

This retrospective single-center analysis studied the impact of the conditioning and the graft-versus-host disease (GVHD) prophylaxis on outcome in unselected patients allografted for chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) secondary to documented prior CMML. A total of 44 patients (median age 61 years) allografted between 2002 and 2019 in our institution were analyzed. Fifteen patients had secondary AML. The conditioning regimen was fractionated 6-8 Gy total body irradiation (TBI) in combination with fludarabine in 33 (75%) patients. Eleven patients (25%) received alkylator-based conditioning therapy without TBI. For GVHD prophylaxis, a calcineurin inhibitor (CNI) backbone in combination with methotrexate (MTX) or mycophenolate mofetil (MMF) was applied in 21 and 23 patients, respectively. All patients allografted from an unrelated donor (UD) received antithymocyte globuline. In univariate analysis of the entire cohort, TBI-based conditioning and MMF-containing immunosuppression were associated with improved leukemia-free survival (LFS, HR 0.16, P < 0.001 and HR 0.41, P = 0.030, respectively). After stratification according to conditioning and GVHD prophylaxis into four groups (TBI-MMF [n = 17], TBI-MTX [n = 16], alkylator-MMF [n = 6], alkylator-MTX [n = 5]), TBI-MMF was associated with improved overall survival (OS) and LFS (P = 0.001 and P < 0.001, respectively). Patient and disease characteristics did not differ between the groups. The associations of TBI-based conditioning and MMF with prolonged LFS were observed across the CMML (n = 29), secondary AML (n = 15), and UD allograft (n = 34) subgroups. In summary, our study suggests that allografting based on intermediate-dose TBI conditioning and MMF-containing GVHD prophylaxis is associated with increased disease control in CMML. Larger (registry-based) studies are warranted to confirm our findings.

Topics: Adult; Aged; Antilymphocyte Serum; Busulfan; Calcineurin Inhibitors; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Male; Melphalan; Methotrexate; Middle Aged; Mycophenolic Acid; Myeloablative Agonists; Neoplasms, Second Primary; Proportional Hazards Models; Retrospective Studies; T-Lymphocytes; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Whole-Body Irradiation