tacrolimus and Leukemia--Promyelocytic--Acute

We encountered a 12-year-old girl with acute promyelocytic leukemia (APL) that occurred 21 months after a living donor partial orthotopic liver transplantation from her father for ornithine transcarbamylase deficiency. FK-506 had been administered for prophylaxis against graft-versus-host reaction. The bone marrow specimen revealed a massive infiltration of promyelocytic blasts (M3 by FAB classification) with chromosome 46, XX, t (15; 17) (q22; q12), being the recipient origin. A PML/RAR alpha chimeric gene was detected by RT-PCR. The patient was diagnosed as having APL and successfully induced to complete remission by chemotherapy including daunorubicin (DNR), cytarabine (araC), and all-trans retinoic acid (ATRA). She has been in continuous remission for 12 months after the treatment. Leukemia after liver transplantation is generally taken as a rare complication. However, recent advances in the survival rate of patients who have undergone liver transplantation will lead to an increase of such cases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Daunorubicin; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukemia, Promyelocytic, Acute; Liver Transplantation; Living Donors; Ornithine Carbamoyltransferase Deficiency Disease; Remission Induction; Tacrolimus; Tretinoin

A major complication following hematopoietic stem cell transplantation is graft versus host disease. Cutaneous manifestations of chronic graft versus host disease (cGVHD) are varied and this condition impacts patient outcomes and quality of life. We describe two cases of lichen sclerosus et atrophicus-like cGVHD developing in patients after hematopoietic stem cell transplantation. Both patients presented clinically with patches of pigmentary changes and scaling that displayed classic histologic features of lichen sclerosus et atrophicus. The skin is a frequent target organ of cGVHD and often the presenting location of the disease, making dermatologists key in recognition and management. It has been proposed that cutaneous cGVHD is a spectrum of disease and the lesions may evolve through various stages. Lichen sclerosus et atrophicus-like cGVHD may represent a phase in this continuum or a distinct sub-type of disease. Remaining cognizant of the potential manifestations of disease is key for prompt recognition and proper treatment.

Topics: Clobetasol; Combined Modality Therapy; Diagnosis, Differential; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Hydrocortisone; Immunosuppressive Agents; Leukemia, Promyelocytic, Acute; Lichen Sclerosus et Atrophicus; Lymphocyte Transfusion; Male; Middle Aged; Photopheresis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tacrolimus; Triamcinolone

Organ transplant recipients are generally considered to be at greater risk for developing malignant disorders because of prolonged immunosuppression for organ grafting, but acute leukemia is a rare complication after organ transplantation (0.2 -2.5%). We encountered two girls with acute promyelocytic leukemia (APL) after living donor partial orthotopic liver transplantation. In one patient, APL developed 21 months after liver transplantation for ornithine transcarbamylase deficiency. She had been administered tacrolimus for prophylaxis of graft-versus-host reaction. In the other patient, APL was diagnosed 46 months after liver transplantation for congenital biliary atresia. Both patients were successfully treated by chemotherapy including all-trans retinoic acid (ATRA), and after reaching complete remission, they have subsequently been in continuous remission. Although leukemia after liver transplantation is generally thought of as a rare complication, increases in survival rate following liver transplantation is likely to lead to more such cases, and documentation of these cases is therefore of importance.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biliary Atresia; Child; Child, Preschool; Cytarabine; Daunorubicin; Female; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukemia, Promyelocytic, Acute; Liver Transplantation; Living Donors; Ornithine Carbamoyltransferase Deficiency Disease; Remission Induction; Tacrolimus; Tretinoin

The macrolide, FK-506, is a potent and effective inhibitor of lymphocyte activation. We studied the effects of FK-506 on human neutrophil activation induced by chemoattractants and by various substances which circumvent receptor stimulation. After preincubation for 5 min at 37 degrees C, FK-506 (1 microM) inhibited N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMet-Leu-Phe)- or platelet-activating factor-induced superoxide production in neutrophils by about 30%. At therapeutic concentrations (0.1-1 nM) FK-506 was ineffective. FK-506 did not inhibit exocytosis and rises in cytosolic Ca2+ concentration [Ca2+]i mediated by these stimuli, and it did not at all inhibit neutrophil activation induced by C5a, leukotriene B4 and 4 beta-phorbol 12-myristate 13-acetate. FK-506 (1 microM) inhibited A23187-induced exocytosis by about 35%, but A23187-induced superoxide production was unaffected. After preincubation for 5 min at 37 degrees C, FK-506 inhibited fMet-Leu-Phe-induced superoxide production in dibutyryl cAMP-differentiated HL-60 cells by about 20%; preincubation with the drug for 24 h did not result in inhibition of superoxide production. FK-506 did not inhibit agonist-binding to formyl peptide receptors and fMet-Leu-Phe-stimulated GTP hydrolysis of heterotrimeric regulatory guanine nucleotide-binding proteins (G-proteins) in membranes from dibutyryl cAMP-differentiated HL-60 cells. FK-506 did not change steady-state and differential polarized phase fluorescence in HL-60 membranes using 1,6-diphenylhexa-1,3,5-triene and 12-(9-anthroyloxy)-stearate as probes. Our results show that FK-506 at supratherapeutic concentrations partially inhibits neutrophil activation. Inhibition by FK-506 of fMet-Leu-Phe-induced superoxide production is rapid in onset and is not due to inhibition of agonist-binding to receptors, interference with G-proteins or protein kinase C, reduction of rises in [Ca2+]i or alteration in physical membrane state.

Topics: Adult; Calcimycin; Calcium; Cyclosporine; Dose-Response Relationship, Drug; Female; Humans; Leukemia, Promyelocytic, Acute; Male; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Superoxides; Tacrolimus; Tumor Cells, Cultured