tretinoin and Polycystic-Kidney-Diseases

We report a 55-year-old man who began undergoing hemodialysis for polycystic kidney disease 17 years ago. Because pancytopenia and susceptibility to infection were identified, a bone marrow biopsy was performed, resulting in a diagnosis of acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) treatment was initiated, but promyelocytic leukemia/retinoic acid receptor alpha gene fusion without remission was identified by fluorescence in situ hybridization. We administered ATRA/arsenic trioxide (ATO) combination therapy for therapy-resistant APL and confirmed molecular genetic remission. The ATRA/ATO combination therapy was continued, obtaining complete remission 2 years after commencement of treatment. Cystic infections continued during ATRA/ATO combination therapy, similar to infections before APL morbidity, and there were no adverse events leading to treatment discontinuation. ATRA/ATO combination therapy is considered a safe and effective treatment for therapy-resistant APL patients on hemodialysis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Humans; In Situ Hybridization, Fluorescence; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Polycystic Kidney Diseases; Remission Induction; Renal Dialysis; Treatment Outcome; Tretinoin

Diseases affecting the kidney constitute a major health issue worldwide. Their incidence and poor prognosis affirm the urgent need for the development of new therapeutic strategies. Recently, differentiation of pluripotent cells to somatic lineages has emerged as a promising approach for disease modelling and cell transplantation. Unfortunately, differentiation of pluripotent cells into renal lineages has demonstrated limited success. Here we report on the differentiation of human pluripotent cells into ureteric-bud-committed renal progenitor-like cells. The generated cells demonstrated rapid and specific expression of renal progenitor markers on 4-day exposure to defined media conditions. Further maturation into ureteric bud structures was accomplished on establishment of a three-dimensional culture system in which differentiated human cells assembled and integrated alongside murine cells for the formation of chimeric ureteric buds. Altogether, our results provide a new platform for the study of kidney diseases and lineage commitment, and open new avenues for the future application of regenerative strategies in the clinic.

Topics: Animals; Cell Culture Techniques; Cell Differentiation; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Kidney; MCF-7 Cells; Mesoderm; Mice; Polycystic Kidney Diseases; Regenerative Medicine; Stem Cell Transplantation; Tissue Culture Techniques; Tretinoin

Although all-trans retinoic acid (ATRA) is widely used in acute promyelocytic leukemia (APL), there is little data as to whether or not ATRA is useful for patients with liver and renal failure. A 63-year-old APL patient, complicated by Child-Pugh class A liver cirrhosis and chronic renal failure (creatinine 3.2 mg/dL), was successfully treated with 45 mg/m(2)/day of ATRA. With three courses of chemotherapy, complete remission has been maintained for four years in this patient. Serum trough and maximum ATRA concentration, and the area under the curve (AUC) were not elevated. These observations suggest that full-dose ATRA therapy might be safely applicable to such a complicated case with APL.

Topics: Antineoplastic Agents; Humans; Hypercalcemia; Kidney Failure, Chronic; Leukemia, Promyelocytic, Acute; Liver Cirrhosis; Liver Failure; Male; Middle Aged; Polycystic Kidney Diseases; Remission Induction; Tretinoin

Some cases of acute myeloid leukemia following organ transplant (PT-AML) have been published in the literature. We report the second case of acute promyelocytic leukemia (APL), which developed post-transplant and immunosuppressive treatment, in a 50-year-old male who had undergone a renal transplant. At diagnosis he presented typical t(15;17)(q12;q13) with additional abnormalities, including +8,t(13;22)(q12;q13) and an abnormal chromosome 1 which was better characterized by fluorescence in situ hybridization (FISH). He obtained cytological, karyotypic and molecular complete remission (CR) with induction treatment according to the all-trans retinoic acid + idarubican (AIDA) protocol; after 12 months, he relapsed (molecular relapse) and achieved molecular remission with all-trans retinoic acid (ATRA) plus mitoxantrone and cytosine arabinoside. After a further 14 months, he was treated with arsenic trioxide for cytological relapse and obtained a third CR; at the cytological relapse the karyotype showed 47,XY,+8, t(15;17)(q22;q21),t(13;22)(q12;q13),der(22)t(1;22)(p22;q13). He is alive 3.3 years after diagnosis of APL. Cyclosporin A (CsA) was given during all cycles of chemotherapy. We did not observe any severe infections or kidney failure during treatments. The use of conventional cytogenetic analysis plus FISH may identify complex karyotype also in transplanted patients receiving immunotherapy, and may also contribute to a better assessment of PT-AL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromosome Aberrations; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 22; Cytarabine; Humans; Idarubicin; Immunosuppressive Agents; In Situ Hybridization, Fluorescence; Kidney Transplantation; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Mitoxantrone; Polycystic Kidney Diseases; Recurrence; Remission Induction; Reverse Transcriptase Polymerase Chain Reaction; Tretinoin

Topics: Darier Disease; Etretinate; Humans; Male; Middle Aged; Pedigree; Polycystic Kidney Diseases; Tretinoin