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Although an activating mutation of Ras is commonly observed in myelodysplastic syndrome (MDS), the role of Ras in the natural history of MDS remains largely unknown. We prospectively studied efficiency and tolerance of lonafarnib, a compound able to inhibit Ras signalling pathway through an inhibition of farnesyl transferase, in patients with MDS or secondary acute myeloid leukaemia (sAML). Lonafarnib was administered orally at a dose of 200 mg twice daily for three courses of 4 weeks (separated by 1 to 4 weeks without treatment). Sixteen patients were included: FAB/RAEB (n = 10), RAEB-T (n = 2), sAML (n = 2) and chronic myelomonocytic leukaemia (CMML; n = 2); WHO/RAEB-1 (n = 4), RAEB-2 (n = 5), AML (n = 5), CMML (n = 2). Median age was 70 (53-77) years. The karyotype was complex or intermediate in 11 patients, and the International Prognostic Scoring Systems (IPSS) risk groups were low in two patients, INT-1 in one patient, INT-2 in four patients and high in six patients (unknown or not applicable in three patients). Among the 14 patients tested, five had Ras mutations in codons 12, 13 or 61 of N-Ras, K-Ras or H-Ras. One patient was excluded of the analysis for protocol violation, and 15 patients were assessable for tolerance. Gastrointestinal toxicities (diarrhoea, nausea and anorexia) and myelosuppression were the major side effects. Other toxicities included infections, fatigue, increase of liver enzymes, arrhythmia and skin rash. One patient died of infection, and the treatment was stopped in one other who developed atrial fibrillation. Doses were reduced in all but one patient treated with more than one course of farnesyl transferase inhibitor. Responses were assessable in 12 patients. A partial response in one sAML patient and a very transient decrease of blast cell count with normalisation of karyotype in one MDS patient were observed. No relation between improvement of marrow parameters and detected Ras mutations was observed. Lonafarnib alone, administered, Clinical Trial, Phase II, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

We report the case of a 79-year-old woman with a longstanding lymphedema of the right arm who developed a skin lymphoma involving the right wrist area. Microscopically, the lesion was composed of numerous centroblasts infiltrating both the dermis and the subcutaneous tissue. Phenotypic investigations showed expression of CD20, CD79a, and bcl-2 protein by neoplastic cells. In addition, these cells were CD5 positive. No expression of anaplastic large cell lymphoma kinase (ALK), CD10, CD23, CD30, CD43, bcl-6, cyclin D1, p53 or p16INK4a could be seen. Polymerase chain reaction (PCR) analysis demonstrated a clonal rearrangement of the genes coding for the kappa light chain of the immunoglobulin (Ig). No rearrangement of the genes coding for the Ig heavy chain, t(14;18) or t(11;14) chromosome translocations, or Epstein-Barr virus (EBV) genomic sequences could be found. The tumor was classified as stage IE and was first cured by complete surgical excision. Nineteen months later, a recurrence was noted in the right elbow area. This study further illustrates that lymphoma of the skin may complicate chronic limb lymphedema. Like most of the previously reported cases, this neoplasm belonged to the category of diffuse large B-cell lymphoma. However, it showed CD5 expression as a singular feature., Case Reports, Journal Article, Review, SCOPUS: ar.j, info:eu-repo/semantics/published

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We report the findings in 21 Belgian patients (12 males and 9 females, median age 61 years) with LGLPD. Symptoms at presentation included infection (n = 9), weight loss (n = 5), asthenia (n = 9). pruritus (n = 2) and arthralgia (n = 7). Four patients were asymptomatic. The main clinical findings were hepatomegaly (n = 5), splenomegaly (n = 8), lymph node enlargement ( n = 3) and arthritis (n = 5). All patients had an increased LGL count associated with anemia (n = 12), neutropenia (n = 17), often < 0,5 . 10(9)/L (n = 10) and thrombocytopenia (n = 6).Three patterns of lymphocyte surface markers were observed: CD3+CD4-8+(14 patients), CD3+CD4-8+(5 patients) and CD3+CD4+8-(1 patient). An abnormal karyotype was found in 2 patients. T-cell receptor gene was rearranged in all cases tested (9/9). Our findings are in agreement with recent data from the literature.

Journal Article, info:eu-repo/semantics/published

avec l'équipe de l'Unité Stérile, info:eu-repo/semantics/published

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Between 1987-1988 we treated, in a cooperative study, 13 patients in blast crisis of CGL according to Koller and Miller's regimen. We observed no return to the chronic phase of the disease, while some patients suffered major drug-induced side effects. Six patients in accelerated phase were treated with the same combination therapy. All of them responded with a return to the chronic phase for a median of 4.5 months. In our hands the combination of plicamycin and hydroxyurea was ineffective in patients with CGL in blast crisis. This regimen could deserve further evaluation in patients with CGL in acceleration.

We have compared the effect of alpha 2-C and gamma recombinant interferons (rIFNs) on normal myeloid progenitors (N-CFU-GM), chronic myeloid leukemia (CML) progenitors (CML-CFU-GM) and leukemic progenitors (L-CFU) of acute non-lymphoblastic leukemia (ANLL) patients. Within 14 days of continuous exposure in culture, a dose-dependent inhibition of CFU-GM was seen for most normal subjects. Resistance to rIFNs was frequent in leukemic patients and even more in acute leukemia than in CML. Stimulation of clonogenic cell growth was seen for a minority of leukemic patients. When only the sensitive cases were considered, no difference in sensitivity was noticed between normal, CML and ANLL patients. A good correlation was observed between the activity or the lack of activity of alpha and gamma rIFNs., Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, FLWNA, info:eu-repo/semantics/published

Basophilic leukemia is a rare disease accounting for less than 2% of all hematopoietic malignancies and little is known about the best therapeutical approach. We report a case of basophilic leukemia occurring as an accelerated phase of chronic myelogenic leukemia in a 50 year old man with a past history of uranium and thorium exposure. He was successfully treated with intensive chemotherapy and total body irradiation followed by autologous peripheral stem cell transplantation. Such an approach has never been reported in this disease. However, the benefit on survival could not be evaluated because of a fatal opportunistic infection. The cases of basophilic leukemia reported in the literature are discussed., Case Reports, English Abstract, Journal Article, Review, SCOPUS: re.j, info:eu-repo/semantics/published

The sensitivity of myeloid progenitor cells from normal subjects (N-CFU-GM) and from leukemic patients in complete remission (LR-CFU-GM) to 4-hydroperoxycyclophosphamide (4-HC) were compared to the sensitivity of leukemic progenitor cells (L-CFU) to this drug. The results were expressed as the dose of 4-HC needed to kill 90% (TD 90) of the progenitor cells. The mean TD 90 were respectively for N-CFU-GM :59 (+/- 11 S.E.M.) nM ml-1 and for L-CFU 79 (+/- 6 S.E.M.) nM ml-1. Thus, L-CFU were equally sensitive to 4-HC as N-CFU-GM. Moreover, the mean TD 90 for LR-CFU-GM was 87 (+/- 5 S.E.M.) nM ml-1. Thus, the sensitivity of N-CFU-GM and LR-CFU-GM did not differ significantly from that of L-CFU. These results are not encouraging for the use of 4-HC in vitro to eliminate the residual leukemic cells from autologous bone marrow of AML patients in complete remission. The sensitivity of L-CFU was modified neither by previous cytoreductive therapy (different from cyclophosphamide) nor by the time elapsed since diagnosis of AML., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

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English Abstract, Journal Article, SCOPUS: NotDefined.j, info:eu-repo/semantics/published

Twenty courses of carminomycin were administered to 18 evaluable adult patients with acute leukemia (14 ANLL, 2 ALL, 2 CGL-BC). All but one received daily doses of 6-14 mg/m2 for 5 consecutive days. Two patients older than 60 yr had not prior chemotherapy and the others had refractory or relapsed disease. The median age was 60 yr. Three ANLL patients achieved complete remission for 8, 9 and 9 months respectively, with no maintenance therapy. None of these had proven clinical resistance to daunomycin and/or doxorubicin. Mucositis was dose-related and dose-limiting. Nausea and vomiting were rare. Alopecia was constant. Cardiac arrythmia was ascribed to carminomycin in two patients. One episode of cardiac failure seemed clearly drug-related and recovered with symptomatic treatment. In conclusion, encouraging antileukemic activity was observed with carminomycin in poor-risk patients. At doses up to 12 mg/m2 day X 5, extramedullary toxicity remained acceptable., Journal Article, info:eu-repo/semantics/published

English Abstract, Journal Article, SCOPUS: NotDefined.j, info:eu-repo/semantics/published

The factors which are thought to determine the response of acute leukemia (AL) to therapy are: 1) tumor size 2) drug dose 3) sensitivity to drug, 4) scheduling of drugs and 5) suppression of normal hemopoiesis. Each of these factors is considered in terms of the scientific data supporting their importance. Inability to measure the size of the tumor mass during all phases of treated AL continues to weaken rational strategies for therapy especially maintenance chemotherapy. Increasing the drug dose improves cell kill and potentially the cure rate up to the limits of toxicity. These limits may be extended by bone marrow transplantation. Various systems to study the drug sensitivity of leukemic cells are in experimental use, including stem cell assays but as yet they do not give a guide to altering therapy. The scheduling of multiple drugs is designed to increase cell kill by recruitment into the cycle, but "sanctuaries" appear to exist for resting cells. The suppression of normal hemopoiesis apparently due to leukemia-associated inhibitors is associated with favorable prognosis in childhood ALL but use of this information to improve treatment protocols is still unclear., Journal Article, Review, info:eu-repo/semantics/published

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