Allogeneic bone marrow transplantation for primary myelofibrosis.
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Biomedical subjects
Publications and source records attributed to N Ifrah.
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Gelatinous transformation of the bone marrow in a 79-year-old patient was observed. It was associated with acute leukemia diagnosed on the biopsy of a vertebral body, indicated by previous Indium-transferrin scintigraphy. Though the lesion is usually associated with severe weight loss and cachexia, the rare cases of gelatinous transformation reported among patients with malignant disease are summarized. It is suggested that metastatic changes by blast cells in acute leukemia may lead to gelatinous transformation of bone marrow but this remains to be investigated.
High-dose cytarabine (HDARA-C) is an effective but toxic treatment for acute myeloid leukemia (AML). In order to reduce the incidence of severe complications noted with HDARA-C-containing regimens, we used a combination of intravenous (IV) idarubicin (IDARUB) at optimal dosage and cytarabine (ARA-C) at intermediate dosage. Thirty-five patients aged 23 to 78 years (median, 56) with AML in first relapse received IDARUB, 8 mg/m2/d for five days, and ARA-C, 1 g/m2 every 12 hours for six doses. Of the 35 patients, 21 achieved a complete remission (CR), four had a partial remission (PR), four died in aplasia, and six were nonresponders. The only factor influencing the CR rate was the duration of the first CR (35% for patients relapsing before 16 months v 83% for patients relapsing after 16 months, P = .003). Mucositis was the most significant extrahematologic side effect. Diarrhea, skin toxicity, and hepatic disturbances were rare and mild. There was no cerebellar toxicity, even in 25 patients greater than 50 years of age. This regimen is effective and well tolerated even in elderly patients, and could be used either as induction or consolidation therapy for the treatment of AML.
Seven patients with Philadelphia (Ph) chromosome positive essential thrombocythemia (ET) were investigated for the presence of a rearrangement within the major breakpoint cluster region (M-bcr) using the Southern blot technique and, in six cases, for the presence of the hybrid bcr-abl mRNA using the polymerase chain reaction (PCR). The molecular studies showed rearrangement of M-bcr in all cases; there was evidence of the b2a2 mRNA junction in one case and of b3a2 junction in five cases. These findings are identical to what might have been expected in Ph-positive chronic myeloid leukemia. These features may explain the poor prognosis of Ph-positive ET in comparison with cytogenetically normal cases. Conversely, the differences in clinical presentation may be due to other genetic changes.
Non Hodgkin lymphomas (NHL) of the thyroid are rather uncommon and account for about 7.7 p.100 of the tumours of the gland. They are remarkable by their usual occurrence in patients with Hashimoto's disease and by controversy about their therapy. The clinical features and the course of four additional cases occurring in four female patients (ages ranged from 61 to 73 years) are reported. The clinical picture was that of a quickly growing diffuse or multinodular goiter, squeezing surrounding neck structures. Antithyroid antibodies were present in 3 cases; microscopical examination showed cytologic features of lymphocytic thyroiditis. Two patients died within a few months, the follow-up is about two years for the others. Two main problems are discussed. First, NHL of the thyroid usually occurs in patients with Hashimoto's disease: how to confidently recognize lymphomas by fine needle biopsy in such cases? Second, which is the best treatment? The authors think that lymphomas of the thyroid have to be considered rather as lymphomas than thyroid tumours. Therefore the cure of the disease may need chemotherapy, in some cases associated with radiotherapy according to careful staging and grading in each case.
For monitoring the effect of chemotherapy in acute myeloid leukemia (AML), we attempt to detect minimal numbers of AML clonogenic cells (CFU-L) during remission using light density gradients combined with PHA-LCM methyl cellulose assay. Fifteen patients in complete remission (CR) of AML were studied: 8 patients with Auer Rods (AR+), and 7 without Auer Rods (AR-). The cluster/colonies ratio and the granulocytic maturation of cells from pooled colonies were not significantly different whatever the density cut used (1077, 1062 or 1059). In all the AR+ patients, few AR+ cells (.06% +/- .03) were observed in bone marrow cultures during remission, without differences between density gradients, but not before plating. These AR+ cells were not found in culture of AR- patient bone marrows nor in normal marrows. The serial studies performed in 6 patients (4 AR+, 2 AR-) were not contributive for relapse prediction. In 2 cases, the second examination failed to detect AR+ cells: one was performed after an autologous bone marrow transplantation and the other in a patient with prolonged CR (54+ months). A quantitative analysis of residual CFU-L with our technique requires a cytological examination of each colony, that is very time consuming and limits its routine use.
71 leukaemic patients having HLA-matched bone-marrow transplants (BMT) were randomised to receive whole marrow (group A) or marrow depleted of T cells by treatment with monoclonal antibodies (anti CD4-CD5-CD8, group B; anti CD2-CD5-CD7, group C) plus complement. All patients received cyclophosphamide and total body irradiation before transplantation and cyclosporin after BMT. Marrow treatment removed 97% of T cells (median) in group B and 99% in group C. Although both serious and mild graft-versus-host disease (GVHD) were reduced in T-cell depleted patients, graft failure and relapse were increased. Graft failure was caused by GVHD and transplant complications in the controls and by rejection and relapse in the T-cell depleted groups; relapse-free survival did not differ between the groups. Without better control of host immunity and of the residual leukaemia T-cell depletion of the marrow, BMT should not be pursued in standard-risk patients.
Acute leukaemia is a rare event during the course of chronic lymphocytic leukaemia (CLL), and only a small fraction of such cases have been shown to be true acute lymphoblastic crises. 1 case is described where both small lymphocytes and proliferating lymphoblasts have the same monoclonal pattern as defined by direct immunofluorescence of membrane-bound immunoglobulins. Previous cases are reviewed and do not appear to be mere coincidence: acute blast crisis may represent a part of the natural history of CLL.
Acute lymphoblastic leukemia (ALL) is a heterogeneous entity that can be subcategorized on the basis of morphologic aspects, membrane antigens, caryotypic analysis and enzymatic content of the blast cells. Subgroups corresponding to T cells, Band pre-B cells, and non T non B lymphocytes derivations can be defined by immunologic markers. These studies ease the diagnosis and characterisation of ALL, perhaps their treatment, and enhance understanding of the disease.
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In a series of 22 adult acute lymphoblastic leukemias expressing the common acute lymphoblastic leukemia antigen (cALLA +), eight had marrow lymphocytosis greater than 30% (43 +/- 12%) with disappearance of marrow lymphoblasts and correction of bone marrow insufficiency at the end of the induction treatment. Four of these patients were studied for the cALL antigen at this time and had persistence of this immunological marker (62 +/- 15% of the mononuclear bone marrow cells). The evolution of these patients suggests that these patients were not in complete remission and emphasizes the usefulness of cALLA determination in cases with borderline excess of marrow lymphocytes.
Erythropoietic and granulopoietic expansion after bone marrow transplantation (BMT) are reviewed in 60 allogeneic and autologous BMT. Morphological dyserythropoiesis was more prominent than dysgranulopoiesis. Dyserythropoiesis was present with increased HbF synthesis and i antigen expression. We did not find nocturnal paroxysmal hemoglobinuria and leukocytic alkaline phosphatase level was high. CFU-GM progenitors were still reduced in number 1 year after BMT. The clusters/colonies ratio, increased at day 12 after BMT was normal by day 100. No difference between autologous and allogeneic BMT was observed.
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A spontaneous complete remission of 34 months' duration was observed in an adult patient with acute myeloblastic leukemia. The remission occurred after a severe febrile pneumonia, which was treated with leukocyte transfusions. At relapse, chromosomal abnormalities reappeared slowly. Such spontaneous complete remissions, almost always associated with bacterial infections and blood transfusions, are extremely rare, and are usually of short duration. Previous cases are summarized, and the role of etiologic factors, including those related to the leukemic proliferation, are discussed.
Between January, 1982 and April, 1983, 92 adult patients with acute leukaemia were investigated in our department. According to classical criteria (cytology and optical cytochemistry), 34 were classified as "non-myeloid". These were further tested with a panel of monoclonal antibodies against cell membrane, including ALB1-2 (anti-CALLA), ALB6 (anti-p24), ALB7-8-9 (BA1), OKT and HLA DR; they were also tested for E rosettes, Slg and terminal transferase (TDT). When all these markers but HLA DR were negative, patients were investigated for ultrastructural peroxidases which were found to be present in 2 cases. Among all non-myeloid leukaemias, 18 (56%) were CALLA-positive and TDT-positive acute lymphoblastic leukaemias (ALL), 2 (6%) were ALL T, 7 (22%) were CALLA-negative and TDT-positive ALL and 5 (16%) were acute leukaemias null for our markers, a phenomenon the significance of which is discussed. Patients with the CALLA-negative TDT-positive phenotype were peculiar with regard to age (mean: 50 years), female predominance, L2 cytological pattern according to the FAB classification, good prognosis (complete remission in 100% of the cases) and median survival (p less than 0,03).
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Haematopoietic growth factors play a very important role in the proliferation and maturation of medullary cells. To date, about fifteen of these factors have been characterized and are known to act either on the most immature progenitors, or on the proliferation compartment, or on already mature cells. In fact, myeloid lines depend on complex interactions between these various inductors. All these inductors are made of glycoproteins, and many of them are continuously located on the long arm of chromosome 5, but they do not represent a family of genes. Their receptors are not limited to normal haematopoietic cells, and this lack of selectivity accounts for certain side-effects observed in clinical use and for the (theoretical) risk associated with their use in the treatment of some malignant blood diseases or even solid tumours.