aclarubicin and Graft-vs-Host-Disease

Chemotherapy followed by donor lymphocyte infusion (DLI) is a promising treatment for relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the best strategy for administering this therapy is still unclear. This study sought to explore the efficacy and safety of chidamide and CAG (cytarabine, aclarubicin, and granulocyte colony-stimulating factor) (CCAG) regimen followed by DLI in relapsed AML/MDS after allo-HSCT. This was a single-arm, phase II trial in patients with relapsed AML/MDS after allo-HSCT. CCAG regimen followed by DLI was given according to the inclusion and exclusion criteria. Twenty adult patients were enrolled. The median follow-up time was 12 months. The complete remission (CR) rate was 45% and the partial remission (PR) rate was 5%. The 1-year overall survival (OS) was 56.7% (95% confidence interval (95% CI), 31.6-75.6%), and the median OS was 19 months. The 1-year relapse-free survival (RFS) was 83.3% (95% CI, 27.3-97.5%). Patients relapsing more than 6 months after HSCT and achieving CR/PR after CCAG plus DLI regimen attained significantly higher survival rates. The cumulative incidence of grade III-IV acute graft-versus-host disease (aGVHD) was 9.4%. There was no treatment-related mortality (TRM). These data suggest that CCAG plus DLI regimen is safe and induces durable remission and superior survival in patients with relapsed AML/MDS after allo-HSCT. Trial registration number: ChiCTR.org identifier: ChiCTR1800017740 and date of registration: August 12, 2018.

Topics: Aclarubicin; Adult; Cytarabine; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Lymphocytes; Myelodysplastic Syndromes; Recurrence

A 53-year-old male with myelodysplastic syndrome developed Sweet's syndrome extensively over his left iliac and inguinal regions that was refractory to standard treatment with corticosteroids and chemotherapy, received a stem cell transplant from an HLA-matched unrelated donor, conditioned by reduced-intensity regimen. The patient achieved complete hematological remission, and the cutaneous lesions improved gradually and then disappeared completely despite the patient receiving granulocyte colony-stimulating factor after transplantation and developing acute graft-versus-host disease.

Topics: Aclarubicin; Anemia, Refractory, with Excess of Blasts; Anti-Inflammatory Agents; Bone Marrow Transplantation; Busulfan; Combined Modality Therapy; Cytarabine; Drug Therapy, Combination; Graft vs Host Disease; Humans; Male; Middle Aged; Prednisolone; Remission Induction; Sweet Syndrome; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

The immunosuppressive efficacy of the antineoplastic antibiotic Aclacinomycin A (ACM) was assayed in several test models for humoral and cellular immune response. Humoral immune response, measured as splenic plaque forming cells (PFC) in vitro and in vivo was markedly inhibited by ACM. Suppression of PFC in vivo could be observed when ACM was administered together with the antigen, or three days later. Concomitantly a decrease of circulating antibodies to SRBC was obtained. No effect on T-cell mediated immune response - DTH reaction and allogeneic cytotoxic lymphocytes - or on skin transplantation or a T-cell mediated autoimmune disease, EAE, was observed. ACM beneficially influenced the course of the disease in two GvH-models (hemolytic anemia and immune complex glomerulonephritis) which lead to a B-cell mediated autoimmune disease with fatal outcome. It was concluded that the therapeutic effect of ACM on GvH-disease is mediated via its suppression of the B-cell response.

Topics: Aclarubicin; Anemia, Hemolytic; Animals; Antibiotics, Antineoplastic; Antibody Formation; Encephalomyelitis, Autoimmune, Experimental; Female; Glomerulonephritis; Graft vs Host Disease; Hemolytic Plaque Technique; Immune Complex Diseases; Immunity, Cellular; Immunosuppressive Agents; Mice; Mice, Inbred Strains; Naphthacenes; Rats; Rats, Inbred Lew