tretinoin and Lymphoma--Non-Hodgkin

Topics: Antigens, CD34; Blood Platelets; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Multiple Myeloma; Pilot Projects; Platelet Count; Transplantation Conditioning; Tretinoin

We conducted a phase II study to determine the efficacy and toxicity of 9-cis-retinoic acid (9-cis RA), a pan-retinoid receptor agonist, in the treatment of patients with relapsed and refractory NHL. Patients were eligible if they had histologically documented relapsed or refractory T cell or indolent B cell NHL. The first three patients enrolled received 70 mg/m2 of 9-cis RA orally twice a day, but the remaining patients received a single oral daily dose of 100 mg/m2. After 6 weeks of therapy, tumor response was assessed objectively. Response rate and toxicity were determined in all 29 eligible patients based on an intent-to-treat analysis. Four patients (14%) responded (3 PRs and 1 CR; 95% CI 4%-33%). One patient had a minor response, and eight had stable disease. Responses were observed in two (11%) of 19 patients with B-cell lymphoma and in two (20%) of 10 patients with T-cell lymphoma. The median time-to-treatment failure for the 29 eligible patients was 8 weeks. The most frequent toxic effects were dry skin, headache, hypertriglyceridemia, and hypercalcemia. Five patients discontinued therapy due to toxic side effects, but no toxic deaths occurred during the study. We conclude that 9-cis RA has a modest activity in relapsed and refractory NHL. In this study, responses were observed in patients with B-cell lymphomas and those with T-cell lymphomas.

Topics: Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Calcium; Disease-Free Survival; Female; Follow-Up Studies; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prospective Studies; Recurrence; Therapeutic Equivalency; Tretinoin; Triglycerides

This study aimed to detect the protein expression of HA117 in pediatric solid tumors. Immunohistochemistry was performed to detect the expression of HA117 and P-gp in pediatric solid tumors. In Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), nephroblastoma (WT), and neuroblastoma (NB), the positive expression rate of HA117 was 65.4%, 58.3%, 81.3%, and 74.1%, and that of P-gp was 57.7%, 70.8%, 65.6%, and 66.7%, respectively. HA117 expression was closely related to the clinical stage of HL (P=0.004) and to the International Prognostic Index score, mediastinal lesions, and clinical stages of NHL (P=0.01, 0.03, and 0.01). The expression of HA117 in WT was higher than in adjacent normal tissues, but there was no statistical significance (P=0.21). The positive expression of HA117 in NB was markedly higher than that in normal tissues (P=0.002), which closely associated with histologic type and lymph node metastasis (P=0.03 and 0.001). Spearman correlation analysis revealed that HA117 expression was not correlated with P-gp in these 4 tumors. This suggests that HA117 might be an important resistance gene in pediatric solid tumors. The mechanism underlying the resistance to all-trans retinoic acid conferred by HA117 is different from that of P-gp.

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Hodgkin Disease; Humans; Kidney Neoplasms; Lymphoma, Non-Hodgkin; Male; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Nervous System Neoplasms; Neuroblastoma; Tretinoin; Wilms Tumor

To explore whether the oligonucleotide uptake in hematological tumor cells is related to cellular species and proliferation.. Intracellular mean fluorescence intensity was measured by flow cytometry.. After treatment with FITC-labeled G3139 at the concentration of 0.60 mumol.L-1 for 4 h, the G3139 uptake into peripheral blood mononuclear cell and bone marrow mononuclear cell in hematological tumor patients was significantly higher than that in normal control. There was different uptake of G3139 among the malignant hematological tumor cell strains, and the uptake in cells derived from monocyte, B lymphocyte and myeloid cell was much higher than that in cells derived from T lymphocyte. After treatment with all-trans retinoic acid (ATRA), HL60 cell proliferation was markedly inhibited and the uptake of G3139 decreased significantly.. Hematological tumor cells were capable of taking up oligonucleotide, and the oligonucleotide uptake in hematological tumor cells is related to its cellular species and its activation.

Topics: Biological Transport; Cell Division; Genes, bcl-2; HL-60 Cells; Humans; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Promyelocytic, Acute; Leukocytes, Mononuclear; Lymphoma, Non-Hodgkin; Oligonucleotides, Antisense; Thionucleotides; Tretinoin; Tumor Cells, Cultured

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cyclophosphamide; Cytarabine; Doxorubicin; Etoposide; Female; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasm Proteins; Neoplasms, Second Primary; Oncogene Proteins, Fusion; Piperazines; Prednisolone; Remission Induction; Tretinoin; Vincristine

We report a patient who developed acute promyelocytic leukemia (APL) concomitantly with a second relapse of non-Hodgkin's lymphoma (NHL), intermediate grade, WF type E. At diagnosis and at first NHL relapse, the patient had received the same chemotherapy regimen, which included drugs targeting DNA topoisomerase II, i.e., etoposide (total dose 5,760 mg) and idarubicin (total dose 180 mg). Thirty-eight months after initial treatment, the patient showed pancytopenia associated with lymphoma recurrence. Bone marrow examination revealed the presence of atypical promyelocytes with Auer rods; cytogenetics showed t(15;17), and molecular analysis detected promyelocytic leukemia-retinoic acid receptor alpha rearrangement. APL reached complete remission after all trans retinoic acid therapy, whereas NHL did not respond to further chemotherapy. In the literature, five other patients developed APL after treatment for lymphoma, from a total of 59 patients developing sAPL after treatment for any type of neoplasia.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Bone Marrow; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Enzyme Inhibitors; Etoposide; Female; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Lymphoma, Non-Hodgkin; Middle Aged; Receptors, Retinoic Acid; Recurrence; Topoisomerase II Inhibitors; Translocation, Genetic; Tretinoin

Oral retinoids are effective in the treatment of patients with a variety of malignant and nonmalignant skin disorders, including mycosis fungoides. We treated six patients with cutaneous T-cell lymphomas with isotretinoin 1 to 2 mg/kg/d. All patients experienced symptomatic relief (fading of skin lesions and disappearance of pruritus) within two to eight weeks of starting the drug therapy; pretreatment and posttreatment biopsy specimens were unchanged. Adverse effects were minor and primarily consisted of drying of the mucous membranes. We conclude that isotretinoin is a well-tolerated, easily administered drug that provides good palliation of symptoms and signs associated with cutaneous T-cell lymphoma in patients who are unable or unwilling to comply with standard therapy.

Topics: Aged; Female; Humans; Isotretinoin; Lymphoma, Non-Hodgkin; Male; Middle Aged; Skin Neoplasms; T-Lymphocytes; Tretinoin; Xerostomia

The presence and level of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) were determined in several neoplastic cell lines. These cells exhibited different degrees of susceptibility to growth inhibition in culture by two retinoids, retinyl acetate and retinoic acid. CRABP was detected in 10 and CRBP in 3 of the 11 tested cell lines. The levels of CRBP and CRABP were in the ranges 15-3,400 and 4-1,290 pmol per 10(9) cells, respectively, as determined by sucrose gradient centrifugation. Cell lines that contained CRABP included S91 and B16 melanomas; Mm5mT and DMBA No. 8 mammary adenocarcinomas; BW5147, BW5147.RicR, and P3 neoplastic lymphoid cells; F361.2 (a hybrid cell line obtained by fusion of MSV3T3 and BW5147); MSV3T3 sarcoma; and RAW8 lymphosarcoma. All but the last two cell lines were inhibited by retinoic acid in culture. CRBP was detected in extracts of S91, Mm5mT, and RAW8. Retinyl acetate inhibited the growth of all cell lines with the exception of RAW8, MSV3T3, and F361.2. No correlation was found between the level of either binding protein and the extent of growth inhibition by either retinyl acetate or retinoic acid. Neither of the binding proteins was detected in L1210-A5 leukemia cells, whose proliferation can be inhibited by both retinyl acetate and retinoic acid. These data indicated that screening cell lines for the presence and level of CRBP and CRABP is not sufficient to predict the susceptibility of cultured cells to growth inhibition by retinoids.

Topics: Adenocarcinoma; Animals; Carrier Proteins; Cell Count; Cell Line; Leukemia; Lymphoma, Non-Hodgkin; Melanoma; Mice; Neoplasms, Experimental; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Sarcoma; Tretinoin