Comparison of chemotherapy and autologous and allogeneic transplantation as postinduction regimen in adult acute lymphoblastic leukemia: a preliminary multicentric study.
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Biomedical subjects
Publications and source records attributed to A Broustet.
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Recent progress in immunopathological studies of peripheral nerve and lymph node fragments together with 16 personal cases and numerous clinicopathological reports have suggested a new classification of peripheral neuropathies (PN) and lymphomas. These are: (1) PN due to local infiltrations by a T-cell lymphoma: (2) acute polyradiculoneuritis due to active demyelination and associated with infiltrates of a T-cell lymphoma in the epineurium, resembling Marek's disease (which is a T-cell lymphoma); (3) B-cell lymphoma proliferation which may be restricted to or predominate in the peripheral nervous system, with a large clinicopathological heterogeneity ranging from localized forms to ascending polyradiculoneuropathies; (4) angiotropic lymphoma, which is a B-cell lymphoma and may present as an acute mononeuropathy; (5) patients with acquired immunodeficiency syndrome due to lymphomatous infiltrates in the endoneurium, of which 2 cases of PN have been reported; (6) PN associated with organomegaly, endocrinopathy, M-component and skin lesions, certain cases being associated with a plasmocytoma and sometimes Castleman's disease but without any monoclonal gammopathy: (7) classic Guillain-Barré syndrome, prone to develop in patients with extraneural lymphoma but without any lymphomatous infiltrates in the peripheral nervous system; (8) certain cases (4 out of 16 in our series) where there is no clear relationship between PN and lymphoma, and there are mainly features of axonal degeneration. Inflammatory perivascular infiltrates were sometimes present in the epineurium.
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Ninety-two elderly patients (ages 50-70) with "de novo" acute myeloid leukemia were given induction chemotherapy consisting of aclacinomycin-A (ACLA) (100 mg/m2/day x 3) and cytosine arabinoside (ARA-C) (100 mg/m2 day, continuous infusion, 7 days). Fifty-one patients (55%) achieved complete remission (CR), 8 patients exhibited drug resistance and 33 patients died during chemotherapy or aplasia. Three patients had severe cardiac toxicity. The only prognostic factor significantly affecting CR was the initial leukocyte count. After consolidation using ACLA (80 mg/m2/day x 2) and ARA-C (100 mg/m2/day x 5), 47 CR patients were randomly assigned to 2 different treatment arms: 23 patients (Group A) received intensive sequential chemotherapy consisting of 4 monthly courses of 8 different drugs while 24 other patients (Group B) were given ACLA and ARA-C at regular intervals, associated with continuous chemotherapy consisting of 6-mercaptopurine, methotrexate and androgens. The probability of disease-free survival at 2 years was significantly higher (33 +/- 22%) for Group B patients than for Group A (13 +/- 16%) (P less than 0.05). We conclude that continuous maintenance chemotherapy may be useful in increasing the number of long-term survivors, at least in the elderly who have not received very intense consolidation chemotherapy following CR.
A case of undifferentiated malignant tumor of the stomach is reported. The immunohistochemistry of biopsy specimens pointed to a diagnosis of carcinoma, the tumor cells being cytokeratin positive and leukocyte common antigen (LCA) negative. After resection, however, histopathologic results showed that the tumor was a large cell lymphoma with plasmablastic differentiation. A new immunohistologic study confirmed, on the one hand, the diagnosis of lymphoma with its monotypic character IgA kappa and, on the other, positivity with three different cytokeratins of the lymphoma cells and their negativity with LCA. The aberrant immunophenotyping of this lymphoma is exceptional and must not undermine the recognized usefulness of LCA and cytokeratin, which both are basic antibody markers of immunohistochemistry in undifferentiated malignant neoplasms.
We report two first cousins with xeroderma pigmentosum who developed a refractory anaemia with excess of blasts which resulted in their deaths.
Autologous blood stem cell transplantation (ABSCT) is a new technique which has been increasingly used in recent years. It is now well established that ABSCT can be performed as safely as autologous bone marrow transplantation (ABMT) when high numbers of hemopoietic precursors are infused. Multiple leukophoreses are performed during marrow regeneration following chemotherapy-induced aplasia. Hemopoietic recovery (predominantly the granulocytic series) is probably faster after ABSCT than after ABMT. Among other advantages there may be minimal contamination by residual tumor cells in buffy-coats; however, this has not been fully investigated.
This article reports 18 cases of acute nonlymphocytic leukemia (ANLL) and abnormal chromosome 16. Thirteen had the same hematological pattern at diagnosis, i.e., peripheral blood hyperleukocytosis with high percentage of monocytes and blast cells, and bone marrow showing three different cell populations: (a) myeloblasts, (b) monocytes and promonocytes, and (c) abnormal eosinophils. In these cases the diagnosis was acute myelomonocytic leukemia with bone marrow eosinophilia, as described. However three other cases were of the M5 type and two others of the M2 type, all showing an abnormal eosinophilia in their bone marrow. All cases showed an abnormal chromosome 16 in the bone marrow cells: inv (16) in 13 cases, t (16;16) in two, del (16) in one of poor quality, and in two other translocations involving band 16q22. In one case the inv (16) was found in a subclone, indicating that it could be a secondary cytogenetic defect. Five patients died soon after diagnosis; the other 13 had a median complete remission duration of 8 months. The central nervous system was frequently involved upon relapse. We do not support the hypothesis that patients with M4-Eo ANLL and chromosome 16 abnormality have a favorable prognosis.
In a prospective study, 157 patients with prolonged aplasia (PMN less than 500/mm3 during more than 21 days), hospitalized in a protected environment unit, were randomly assigned to receive ceftazidime alone or cefotaxime + tobramycin for initial febrile episodes. Age, sex, underlying diseases, duration of neutropenia, digestive decontamination regimen, clinical and microbiological characteristics of infections were similar in the two groups. Patients were evaluated for their initial response to antibiotics (defervescence in 48 hours, maintained 7 days) and long term response (prevention of another infection during aplasia). The overall initial response to ceftazidime was 48/71 (68 per cent) and to cefotaxime + tobramycin 55/86 (64 per cent). The long term response to ceftazidime was 33/71 (46.5 per cent) and to cefotaxime + tobramycin 31/86 (36 per cent). In conclusion, ceftazidime alone was as effective as cefotaxime + tobramycin in the first line treatment of febrile episodes in neutropenic patients.
Peripheral blood stem cells were collected from 50 patients with different hematological malignancies. Leukaphereses (n = 263) were performed during the marrow regeneration phase following different types of chemotherapy. The mean number of CFU-GM collected per leukapheresis was 486 x 10(4), highest levels of CFU-GM being obtained in patients who received the most intensive chemotherapy and who had not been treated previously. Twenty-five patients underwent autologous blood stem cell transplantation. Hemopoietic recovery was complete and prompt in 24 patients. Only one patient had no megakaryocytic engraftment. These findings indicate that peripheral blood stem cells may be used for autologous transplantation in leukemic patients.
Leu-M1 is a differentiation antigen present in human myelomonocytic cells. Seventy-seven acute leukaemias were retrospectively stained with anti-Leu-M1 using the immunoperoxidase technique on Bouin-fixed paraffin-embedded sections. The subjects were 44 acute lymphoblastic leukaemias (ALL) and 33 acute myeloid leukaemias (AML) previously characterized by cytochemical and immunologic (cell suspension) methods. Leu-M1 was positive in all the AML and in half of the ALL cases. These results suggest that Leu-M1 does not allow differentiation between AML and ALL. For the ALL cases Leu-M1 was positive in 15/28 B-cell types, 4/12 T-cell type and 3/4 'null'-cell type cases. Thus, this antibody is of no assistance in defining types B, T, or 'null' in ALL. Leu-M1 was also studied on paraffin sections of 34 high grade malignant lymphomas. The antibody was negative in all 13 B-cell lymphomas (lymphoblastic: 6; immunoblastic: 7) and in all 4 'null' cell lymphomas. It was positive in 4/9 peripheral T-cell type, the other T-cell lymphomas (lymphoblastic: 5; immunoblastic: 3) remaining negative. Thus, Leu-M1 may be positive in T-cell lymphomas but it is negative in B-cell lymphomas and is always negative in B or T lymphoblastic types. It seems that lymphoblasts are Leu-M1 negative in non-Hodgkin's lymphoma and may be Leu-M1 positive in leukaemias.
Bone marrow karyotyping was serially performed in 23 Ph1+ chronic myelocytic leukemia patients treated with allogeneic bone marrow transplantation (BMT). Two patients underwent 2 BMT each. Fifteen patients had only normal karyotypes and 8 patients (after 10 BMT) had either sporadic Ph1+ metaphases (6 cases) or cytogenetic signs of relapse (4 cases, of which in 1 case, without hematological symptoms), or both in succession. Sporadic Ph1+ metaphases were found early after BMT (never after the 6th month). Although they were more frequent in non-splenectomized patients than in others, there was no significant correlation between sporadic Ph1+ metaphases and disease features, treatment regimens or evolution after BMT.
Pyoderma gangrenosum (PG) is an uncommon ulcerative disease of the skin. The cause is unknown but the condition is often associated with other diseases such as rheumatoid arthritis, ulcerative colitis, Crohn's disease or monoclonal gammopathy. The association between PG and haematological malignancies (acute leukaemia, Myeloproliferative disorders) is infrequent. Two cases of PG associated with haemopathy are described; one had primary thrombocythaemia and the other, acute myeloblastic leukaemia following for myeloma. The significance of this association is discussed in the light of other observations previously reported in the literature.
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Eosinophilic leukemias are difficult to individualize amid the hypereosinophilic syndromes. Chromosomal abnormalities when present within the eosinophils are of critical value in the diagnosis of a malignancy. We report here the case of a 27-year-old woman who had been healthy, until recently when she suddenly developed hepatosplenomegaly and lymph node enlargement, and considerable eosinophilia in blood and bone marrow. The morphologically abnormal cells (large pseudo Pelger eosinocytes) predominated in the cytology. The establishment in these cells of a clonal chromosomal anomaly, t(10;11)(p14;q21), favored the malignancy and diagnosis of acute eosinophilic leukemia.
This article reports six cases of acute nonlymphocytic leukemia (ANLL) and an abnormal chromosome #16. All had the same hematologic pattern at diagnosis, i.e., peripheral blood hyperleukocytosis with a high percentage of monocytes and blast cells. The bone marrow showed three different cell populations: (a) myeloblasts, (b) monocytes and promonocytes, and (c) abnormal eosinophils. In three cases, an ultrastructural study confirmed the cytologic data. In all six cases, the diagnosis was acute myelomonocytic leukemia with bone marrow eosinophilia (M4-Eo). All cases showed an abnormal chromosome #16 in the bone marrow cells; in four cases, well-banded chromosomes were obtained, showing a pericentric inversion inv(16)(p13;q22). One patient had a 4-year remission, and another is still in remission 14 months after diagnosis. Three patients relapsed 7, 9, and 20 months after diagnosis. The last patient died soon after diagnosis. Thus, we do not support the hypothesis that patients with M4-Eo ANLL and chromosome #16 abnormality have a favorable prognosis.
Blood-derived hemopoietic stem cells were collected using a continuous (10 patients) or a semi-continuous flow separator (2 patients) in some patients with acute non-lymphocytic leukemia. For ten out of those patients, five to seven leukaphereses were performed during a short period (median = 11 days) of marrow recovery following severe aplasia induced by an intensive chemotherapy. The mean number of CFU-GM cells collected per leukapheresis and per patient respectively was 6.7 X 10(4)/kg and 38.5 X 10(4)/kg. This latter number was similar to that obtained during a marrow harvest performed for a bone marrow transplantation, suggesting that high numbers of hemopoietic stem cells can be collected from the peripheral blood in leukemic patients and used for autologous transplantation.