Biomedical subjects

R Mertelsmann

Publications and source records attributed to R Mertelsmann.

At least 253 records · Page 14Linked to original sources

PubMed1989

Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes.

T cells are known to interact cooperatively with monocytes to produce Colony-Stimulating Factors (CSF), although T cell-mediated signals leading to CSF secretion by monocytes are not completely understood. We have made use of Northern blot hybridization and specific bioassays to study the effects of the T cell product interleukin-4 (IL-4) on monocyte CSF expression. The results suggest a previously unrecognized role of IL-4 as a CSF inducer since exposure of monocytes to IL-4 resulted in accumulation of transcripts for granulocyte-CSF (G-CSF) and macrophage-CSF (M-CSF). Consequently, IL-4-activated monocytes released factors in their culture supernatants biologically and antigenically indistinguishable from G- and M-CSF.

Animals↗

PubMed1989

Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy.

The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematologic parameters was evaluated in a phase I clinical study in 18 patients with advanced malignancy. G-CSF was administered once daily as a 30-minute infusion for 14 days; three patients each were treated at increasing dose levels of 1, 3, 10, 30, and 60 micrograms kg-1 day-1. A transient decrease in neutrophil and monocyte counts was observed immediately after the G-CSF infusion, followed by a dose-dependent increase of up to 15-fold. G-CSF-induced neutrophils exhibited an increased O2- radical production, and serum levels of enzymes related to granulocyte turnover, including lysozyme and elastase, were markedly elevated during therapy. A dose-dependent depression of platelet counts occurred in the second third of the treatment course, followed by a spontaneous recovery despite continuing therapy. G-CSF was well-tolerated; minor to moderate bone pain was the most common side effect. The primary course of the malignant diseases studied was not significantly altered. G-CSF appears to be an appropriate means to selectively increase the number of functionally competent polymorphonuclear phagocytes.

Adult↗

PubMed1989

Interleukin-2 and interferon-gamma recruit different subsets of human peripheral blood monocytes to secrete interleukin-1 beta and tumour necrosis factor-alpha.

Exposure of cultured human peripheral blood monocytes (PBMO) to interferon-gamma (IFN-gamma) enhances surface expression of the p55 subunit of the interleukin-2 receptor (IL-2R). Addition of IL-2 to IFN-gamma treated monocytes will stimulate subsequent release of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) due to enhancement of the transcriptional rate and stability of mRNA accumulation of both genes. The present study was aimed to investigate whether IFN-gamma and IL-2 will favour the release of IL-1 beta and TNF-alpha by different subsets of human PBMO. To this end PBMO were separated into four fractions with densities ranging from 1.058 to 1.075 kg/l by means of discontinuous bovine serum albumin (BSA) gradient centrigugation. Following incubation of monocyte subsets in the presence or absence of IFN-gamma and IL-2 for a culture period of 24-48 h, cell-free culture supernatants were collected and assayed for IL-1 beta and TNF-alpha activity by ELISA. Surface p55 IL-2R expression was detected by CD25 monoclonal antibody (MoAb) anti-IL-2R1 using immunofluorescence analysis. Although IL-2R1 expressing PBMO were equally distributed among the four fractions, IL-1 beta secretion was found to reside mainly in the most dense fraction. The major TNF-alpha activity was detected, however, in supernatants obtained from cultures of PBMO with densities of 1.065-1.075 kg/l. These data demonstrate functional heterogeneity of subsets of human PBMO with respect to their capacity to produce distinct cytokines.

Cells, Cultured↗

PubMed1989

Granulocyte-macrophage colony-stimulating factor (CSF) and multilineage CSF recruit human monocytes to express granulocyte CSF.

We assessed the capacity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and multilineage (Multi)-CSF to induce release of granulocyte-CSF (G-CSF) by highly purified peripheral blood monocyte (Mo) preparations. Our results reveal that GM-CSF and Multi-CSF, either alone or in a synergistic concert, activate Mo to transcribe G-CSF messenger (m) RNA and release biologically active G-CSF protein into their culture supernatants. G-CSF had no regulatory effect on Mo expression of cytoplasmic G-CSF mRNA levels and G-CSF protein secretion by itself. These differential actions of CSFs provide further insight into self-regulatory mechanisms within the growth factor hierarchy system.

Cell-Free System↗

PubMed1989

Effect of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome with excess blasts.

As part of a broad phase I study of recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF), four patients were treated who had myelodysplastic syndrome (MDS) with excess blasts. The GM-CSF was given daily as an intravenous injection over a period of 30 min for 5 days. A total of 11 cycles were conducted. Each patient received at least two different dose levels. In three patients, three different dosages were delivered. The treatment course was interrupted by a 10-day rest period. Rh GM-CSF was well tolerated, with only minor side effects seen, which included bone discomfort at the lower back, sternum and ribs, and constitutional symptoms such as low grade fever, nausea/vomiting, and mild myalgias. Whereas no increases in platelet and reticulocyte counts were recorded, elevations of absolute neutrophil counts above 100 cells/microliters occurred in all patients. The most striking finding was, however, the development of increases in the number of circulating and bone marrow blast counts that were observed particularly when doses of greater than or equal to 500 micrograms/m2 of body surface area were administered. In line with data demonstrating in vitro induction of proliferation of leukemic blast cells by rh GM-CSF, one may take advantage of blastogenesis induced in vivo that may favor the use of a therapeutic strategy by recruiting quiescent cells into the mitotic cycle which would then represent optimum targets for a subsequent cycle-specific cytotoxic chemotherapy. Such an approach could form the basis for new clinical trials in MDS.

Adult↗

PubMed1989

Comparative trial of cytarabine and thioguanine in combination with amsacrine or daunorubicin in patients with untreated acute nonlymphocytic leukemia: results of the L-16M protocol.

Ninety-six patients with de novo acute nonlymphocytic leukemia (ANLL) were randomized to receive either daunorubicin (50 mg/m2, IV) on days 1-3; cytarabine (Ara-C) (25 mg/m2, IV) bolus, followed by 160 mg/m2 as a continuous IV infusion daily for 5 days and 6-thioguanine (6-TG) (100 mg/m2 po) every 12 hr daily for 5 days (DAT); or amsacrine (190 mg/m2, IV) on days 1-3 with Ara-C and 6-TG at the above doses (AAT). Patients achieving complete remission (CR) then received two courses of consolidation therapy with the same combination that had induced remission but at slightly reduced total doses. Patients less than or equal to age 40 with an HLA-identical sibling donor underwent allogeneic transplantation, usually after consolidation therapy. The remaining patients were then randomized to receive either maintenance therapy (alternating cycles of vincristine/methotrexate, cyclophosphamide/6-TG, daunorubicin/hydroxyurea and Ara-C/6-TG) or no further treatment. Ninety-two patients were evaluable for response. Twenty-five of the 46 patients (54%) who received DAT and 32 of the 46 patients (70%) who received AAT achieved CR (p = 0.13). When patients were stratified by age, however, remission induction advantage with AAT became statistically significant (p = 0.03). Additionally, more patients achieved CR following one course of AAT than following one course of DAT (48% vs 28%, p = 0.03). Overall survival in the AAT group was improved as well (p = 0.01). Too few patients were randomized on the maintenance arm of the protocol to make interpretation meaningful. Non-hematologic toxicity was generally comparable in both arms. In conclusion, patients with de novo ANLL who received AAT had a higher remission incidence and slightly longer survival compared to patients who received DAT. Further investigation of this drug combination in untreated patients with ANLL is warranted.

Age Factors↗

PubMed1989

High-level secretion of tumor necrosis factor-alpha contributes to hematopoietic failure in hairy cell leukemia.

Hairy cell leukemia (HCL) is frequently associated with severe pancytopenia. The authors detected high levels of tumor necrosis factor (TNF)-alpha in the bone marrow serum of patients with HCL and found anti-TNF-alpha neutralizing monoclonal antibodies (MoAbs) to be able to enhance hematopoiesis of HCL patients in in vitro colony assays. As potent producers of TNF-alpha, hairy cells could be identified, thus implicating the malignant population in the pathogenesis of hematopoietic failure due to inappropriate secretion of this cytokine.

Hematopoietic System↗

PubMed1988

Recombinant human granulocyte-macrophage colony-stimulating factor induces secretion of autoinhibitory monokines by U-937 cells.

Colony-stimulating factors are required for survival proliferation, differentiation and functional activation of granulocytes, macrophages and their precursor cells. In the present report, however, we demonstrate antiproliferative activity of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) on monoblast cell line U-937 and provide evidence for the involvement of tumor necrosis factor alpha TNF-alpha and interleukin 1 beta (IL 1 beta) in its growth inhibitory action. GM-CSF (but not granulocyte CSF, G-CSF or macrophage CSF, M-CSF) suppressed DNA synthesis and self renewal of U-937 cells. Similarly, medium conditioned by U-937 cells in response to GM-CSF (GM-CSF U-937-CM) was able to reduce clonogenicity and [3H]thymidine uptake by U-937 cells. Since neutralization of GM-CSF present in GM-CSF U-937-CM by monoclonal antibody to GM-CSF did not abrogate the autoinhibitory activity present in GM-CSF U-937-CM, we considered the possibility that other soluble molecules are released by U-937 cells upon GM-CSF stimulation. Neutralization by antibodies to IL 1 beta and TNF-alpha suggested that both monokines could be the antiproliferative principle operating in GM-CSF U-937-CM. Moreover, employing IL 1 beta-specific enzyme-linked immunosorbent assay, TNF-alpha specific radioimmunoassay, Northern analysis using a cloned TNF-alpha-specific cDNA and an oligonucleotide probe for IL 1 beta, we demonstrate GM-CSF-inducible IL 1 beta and TNF-alpha gene expression by U-937 cells at the mRNA and protein level. Although M-CSF expression was induced under similar conditions, M-CSF failed to inhibit growth of U-937 cells.

Adult↗

PubMed1988

The suppressive effects of recombinant human tumor necrosis factor-alpha on normal and malignant myelopoiesis: synergism with interferon-gamma.

The modulation of growth of normal and leukemic myeloid progenitor cells in soft agar cultures by recombinant human tumor necrosis factor-alpha (TNF alpha) and recombinant human interferon-gamma (IFN gamma) was investigated. TNF alpha inhibited colony formation of all colony types representing different maturational stages of normal progenitor cells committed to the myeloid lineage with different orders of sensitivity. Blast-type colonies derived from patients with acute myelogenous leukemia were more sensitive to TNF alpha inhibition than progenitor cells purified from normal bone marrow or bone marrow from patients with stable-phase chronic myelogenous leukemia. The response of most colony types to IFN gamma was poor. However, when IFN gamma was administered together with TNF alpha, synergistically enhanced antiproliferative effects were detected in all colony types tested. The antiproliferative action of IFN gamma on myelopoiesis was enhanced in culture by the presence of autologous monocytes, presumedly by inducing endogenous production of TNF alpha. However, TNF alpha seemed to act directly on the progenitor cells themselves to suppress their clonal growth, rather than involving accessory marrow elements such as monocytes and/or T lymphocytes.

Antibodies, Monoclonal↗

PubMed1988

A phase I trial of intraperitoneal recombinant interleukin 2 in patients with ovarian carcinoma.

Seven patients with refractory stage III ovarian carcinoma were treated with escalating doses of human recombinant interleukin 2 (rIL-2) administered via the intraperitoneal (IP) route in an attempt to establish a dose and schedule of rIL-2 suitable for prolonged outpatient IP administration. Three patients went on to receive outpatient maintenance treatment twice weekly for 2-3 months. Doses ranged from 10(5) to 5 x 10(7) U/m2. The dose found most suitable for twice weekly outpatient IP administration was 10(6) U/m2. Dose-limiting toxicities consisted of diarrhea resulting in hypovolemia (5 patients) fever and chills (4 patients), nausea and vomiting (1 patient), mental status changes (2 patients), and azotemia (1 patient). These side effects were not prevented by indomethacin. Significant hypotension was not observed. Pharmacokinetic studies revealed extremely high IP concentrations of IL-2 which persisted for more than 24 hours. After a dose of 10(6) U/m2, the IP concentrations ranged from 670 to 760 U/ml. In one patient in whom concurrent serum concentrations were determined, the IP concentrations were over 100-fold higher than serum levels. After a dose of 10(7) U/m2, the IP concentrations of IL-2 ranged from 8700 to 14000. Concurrent serum levels in one patient revealed IP concentrations over 500-fold higher than serum levels. There were no consistent changes in T cell surface and activation markers on mononuclear cells from peripheral blood in 3 patients tested. Natural killer cell (NK) activity in peripheral blood increased in the three patients in whom it was measured. Four of the 7 patients progressed on treatment; 3 patients remained stable. We conclude that 10(6) U/m2 of rIL-2 is well-tolerated when administered by the IP route and that concentrations of IL-2 well in excess of that required to enhance cell-mediated cytotoxicity in vitro persist in the IP fluid for at least 24 hours.

Adult↗

PubMed1988

Identification and purification of human erythroid progenitor cells by monoclonal antibody to the transferrin receptor (TU 67).

Anti-TU 67 is a murine monoclonal antibody that recognizes the transferrin receptor. With respect to hematopoietic cells TU 67 is expressed by human multipotent colony-forming cells (CFU-Mix), erythroid progenitor cells (BFU-E and CFU-E) and a fraction of granulocyte/monocyte colony forming cells, but is not expressed by mature hematopoietic cells including erythrocytes, platelets, lymphocytes, and peripheral blood myeloid cells. The TU 67-positive fraction of normal bone marrow, separated by fluorescence-activated cell sorting (FACS) or immune rosettes, contained 87% of the erythroid progenitor cells. Erythroid progenitor cells were enriched up to 50-fold by using a combination of monoclonal antibodies to deplete mature hematopoietic cells, followed by positive selection of BFU-E and CFU-E by TU 67 antibody.

Antibodies, Monoclonal↗

PubMed1988

Incidence of lineage promiscuity in acute myeloblastic leukemia: diagnostic implications of immunoglobulin and T-cell receptor gene rearrangement analysis and immunological phenotyping.

Sixty-nine blood or bone marrow samples from both children and adults with acute myeloblastic leukemia (AML) were investigated to elucidate the frequency of immunoglobulin (IG) and T-cell receptor (TCR)-gene rearrangements. Non-germline configuration for the IG heavy chain (h) gene was detected in the specimens of nine patients of various subtypes according to the French-American-British classification (FAB), including FAB M1, M2, M4 and M5. Rearrangement of the IG kappa chain (k) gene was present in one of these cases which simultaneously revealed a rearranged TCR-beta (b) chain gene. In another two AML samples we found TCR-b gene rearrangements, in one case in combination with an IG-h gene rearrangement. IG-h gene rearrangements were detected in 10 cases, in one case in conjunction with an IG-kappa (k) and TCR-b gene rearrangement. A highly significant correlation between the occurrence of DNA rearrangements of the IG-h locus and nuclear staining with the enzyme terminal deoxynucleotidyl transferase (TdT) and surface expression of the CD 19 and CD 34 antigen could be identified: all 10 TdT positive AML samples rearranged IG-h. Similarly, six out of 69 AML samples exhibited surface expression of CD 19, five of these in combination with CD 34 and all of them rearranged the IG-h gene. The one leukemia with TCR-b gene rearrangement only was TdT positive as well, but did not express CD 19 or CD 34. We conclude that IG-h gene is rearranged in a substantial proportion of AML, strongly associated with a specific immunophenotype (TdT+, CD19+, CD34+), whereas TCR-b gene rearrangement appears more rarely. No positive correlation between occurrence of IG-h and TCR-b gene-rearrangements and one AML FAB-subtype was found, although a clustering of M1 and M4 FAB subtypes in the AML group showing reconstructed IG-h gene became evident.

Adult↗

PubMed1988

[Cytokines in tumor therapy].

The use of recombinant cytokines offers a new dimension in cancer treatment. While the effects of cytotoxic chemotherapy are relatively nonspecific and affecting all rapidly proliferating tissues, these hormone-like, physiologically produced substances are able to modulate tumor-host interactions and in addition may interact with pathogenetically relevant disturbances in growth related cellular functions. The latter principle seems to be of major importance for the impressive results of interferon alfa treatment in hairy cell leukemia. The expected anti-tumor effects of tumor necrosis factor alfa and of interleukin-2 activated killer cells, however, have only been observed in occasional patients, most of them with rare tumors. A more immediately promising therapeutic approach seems to be at hand with the hemopoietic growth factors. They are able to stimulate the non-specific system of host defense as well as the hemopoietic progenitor cell compartment, relevant for reconstitution after aplasiogenic chemotherapy and bone marrow transplantation and thus in near future could be of great importance in the treatment of tumor diseases.

Growth Substances↗

PubMed1988

Yeast-expressed granulocyte-macrophage colony-stimulating factor in cancer patients: a phase ib clinical study.

The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was investigated in 29 patients with advanced malignancy in phase Ib trial. Patients were treated at six different dose levels (30-1000 micrograms/m2/day) with either daily intravenous bolus injection or 24 hours continuous infusion for 5 days or 2 weeks. Administration of rh GM-CSF resulted in a broad spectrum of dose-, route-, and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total white blood cell (WBC) count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a shift to immature myeloid elements. Elevation of lymphocytes, platelets and reticulocytes was not induced. Within one week after discontinuation of treatment the leukocytosis had disappeared. Adverse reactions encountered with rh GM-CSF seen in 65% of the patients studied were never life-threatening and always reversible. They included mild myalgias, facial flushing, low-grade fever, headache, bone discomfort, nausea, dyspnoea and transient decline of platelet counts. These results suggest that rh GM-CSF can be safely administered at the doses and schedules employed and that it can induce in vivo some of the biological effects reported in in vitro studies. Although no objective antitumour responses have been seen, the ability of rh GM-CSF to increase turnover and function of leukocytes in vivo may prevent neutropenia and infections, when GM-CSF is adjunctively added to cytotoxic cancer therapy.

Adult↗

PubMed1988

Amsacrine with high-dose cytarabine is highly effective therapy for refractory and relapsed acute lymphoblastic leukemia in adults.

Thirty-six patients with relapsed acute lymphoblastic leukemia (ALL) and four with primary refractory ALL were treated with a regimen that included amsacrine, 200 mg/m2, intravenously daily for three days with cytarabine, 3 gm/m2, by infusion over three hours daily for five days. There were 27 remissions in the 36 relapsed patients and two in the four patients with primary refractory disease. Seventeen of the 23 patients with common ALL, four of the six with T-cell ALL, one of the three with B-cell ALL, and seven of eight whose cells were not characterized responded. Toxicity of this regimen was comparable to other reinduction regimens for ALL, but the side effects characteristic of high-dose cytarabine therapy were absent. Since these results compare favorably with conventional induction regimens, its use in the primary treatment of adults and children with high-risk ALL is proposed.

Adolescent↗

PubMed1988

Regulation of gene expression of M-, G-, GM-, and multi-CSF in normal and malignant hematopoietic cells.

Colony stimulating factors (CSFs) are produced by a variety of cell types, including T-lymphocytes (T cells) and mononuclear phagocytes; both cell types are known to cooperatively interact to elaborate CSFs, although the specific cellular source of CSF species and mechanisms of intercellular communications in this regard are poorly understood. In this report, we investigate the specific origin of various CSF species in peripheral blood mononuclear cells (PBMC), purified T-lymphocyte and monocyte (Mo) populations. Furthermore, we assess the conditions required for stimulation of purified cell cultures to express CSF messenger RNAs (mRNAs) and proteins. In the absence of exogenous activation stimuli, human PBMC, T cells and Mo failed to produce transcripts for CSF for macrophages (M-CSF or CSF-1), for granulocytes (G-CSF), for granulocytes/macrophages (GM-CSF), and for multilineage CSF (multi-CSF or Il-3). However, after stimulation with phorbol myristate acetate (PMA) and phytohemagglutinin (PHA), mRNAs for M-, G-, GM-CSF, and multi-CSF became detectable in PBMC as early as 6 hours after initiation of cultures. Identical culture conditions resulted in synthesis of G-, and M-CSF mRNA by Mo, whereas T-lymphocytes produced GM-CSF and multi-CSF mRNA. More physiologically, when Mo were activated with interferon (IFN)-gamma or tumor necrosis factor-alpha (TNF-alpha) and T-lymphocytes were stimulated in an Mo-independent pathway, that is via triggering of the 50 kd sheep erythrocyte receptor protein employing monoclonal antibodies (mo ab) to the Tll-2- and Tll-3- defined epitopes, similar kinetics of mRNA expression were obtained. Similarly, when interleukin-1 (Il-1) receptive T cells were stimulated with Il-1, T cells transcribed functionally active GM-CSF and multi-CSF. Maximum peak activity of GM-, G-, and M-CSF protein secretion was identical for all CSF species investigated, and occurred in culture 48-72 hours after specific induction. Constitutive expression of CSFs not found in unactivated normal hematopoietic cells was, however, frequently observed in blast cell populations of patients with acute myeloblastic leukemia. Of 49 AML samples, 15 revealed G-CSF transcripts; 11, GM-CSF mRNA; and 6 samples synthesized M-CSF mRNA. Employing specific bioassays, 12 of 15 G-CSF-mRNA-producing cell populations, 8 of 11 GM-CSF-mRNA-producing cell populations, and 1 of 6 M-CSF-mRNA-synthesizing samples, demonstrated release of the respective functionally active CSFs into their culture supernatants.(ABSTRACT TRUNCATED AT 400 WORDS)

Blotting, Northern↗

PubMed1988

Constitutive expression of hematopoietic growth factor genes by acute myeloblastic leukemia cells.

Blast cell populations of forty nine individuals with acute myeloblastic leukemia (AML) were investigated for constitutive expression of genes for various hematopoietic growth factors. Fifteen samples constitutively exhibited messenger (m) RNA for colony stimulating factor for granulocytes (G-CSF). Eleven AML specimens produced mRNA specific for CSF for granulocyte and macrophages (GM-CSF). When probed for CSF for macrophages (M-CSF or CSF-1) specific hybridization signals became detectable in six samples. Five out of six blast cell populations transcribing M-CSF, synthesized G-, and GM-CSF mRNA's simultaneously, whereas another five leukemias transcribed G-, and GM-CSF genes exclusively. Furthermore, when specific bioassays were performed to detect secretion of biologically active CSF proteins by these leukemic blast samples, twelve out of fifteen G-CSF mRNA producing cell populations, eight out of eleven GM-CSF mRNA producing cell populations and one out of six M-CSF mRNA synthesizing samples, demonstrated release of the respective, functionally active CSF's into their culture supernatants. Our results show that gene transcription and protein secretion of hematopoietic growth factors are features that are frequently detected in leukemic myeloid blast cells and involve G-, GM-, and M-CSF. With respect to recent findings of receptiveness of leukemic colony forming cells (L-CFC) for proliferative stimuli provided by various hematopoietic growth factors, our findings point out a potential role of autocrineously produced CSF's in the pathophysiology of autonomous proliferation in AML.

Blotting, Northern↗

PubMed1988

Randomized study of 13-cis retinoic acid v placebo in the myelodysplastic disorders.

A double-blind, placebo-controlled randomized trial of 13-cis retinoic acid was performed to determine if the drug has a therapeutic effect in patients with myelodysplastic syndromes (MDS). Sixty-eight evaluable patients with MDS were randomized to receive a single, daily oral dose of either 13-cis retinoic acid (13-CRA, 100 mg/m2) or matching placebo. Treatment was continued, when possible, for a period of 6 months. Determination of response to treatment was based on clinical course, repeat bone marrow biopsies, and aspirates and blood counts (CBC) with WBC differential, platelet, and reticulocyte numbers at specified intervals. No significant difference was noted between the two treatment groups in response to test drug (P = .66). One patient (3%) in the 13-CRA group and two patients (6%) in the placebo group had a minor response. Approximately 30% of patients in both groups had progression of their disease, and progression-free survival was nearly identical. Greater than 90% of the patients receiving 13-CRA developed mild or moderate skin toxicity that was reversible with decreasing or discontinuing the drug. Our study did not find that 13-CRA exerts a beneficial therapeutic effect in patients with MDS.

Clinical Trials as Topic↗