Biomedical subjects
Publications and source records attributed to A Broustet.
A Ph-positive CML patient who had received a peripheral blood stem cell autograft in chronic phase demonstrated a transient regression of the Ph-positive clone with the concurrent appearance of another clone with trisomy 8. This latter clone disappeared when the patient received alpha-interferon.
Two patients suffering from acute myelomonoblastic leukaemia developed clinical evidence of peripheral nerve involvement. In both cases, a peripheral nerve biopsy revealed endoneurial cellular infiltrates which were identified as leukaemic cells by immunocytochemistry. Ultrastructural studies showed mainly axonal damage. Moreover, in one patient, a few features of active demyelination were also observed.
PURPOSE: In a prospective multicenter study, we analyzed the benefits of allogeneic bone marrow transplantation (BMT) in a nonselected group of adult patients with acute lymphoblastic leukemia (ALL) and, by a randomized trial, evaluated the effectiveness of autologous BMT over chemotherapy as postremission therapy in patients younger than 50 years who were not candidates for allogeneic BMT. PATIENTS AND METHODS: After induction therapy that randomized patients to receive one of two anthracycline-containing regimens, either daunorubicin (DNR) or zorubicin (ZRB), patients were assigned to postremission treatment according to age and results of HLA typing. Patients younger than 40 years with an HLA-identical sibling (group 1) were scheduled to receive cyclophosphamide 60 mg/kg on days 1 and 2, total-body irradiation (TBI), and allogeneic BMT. Patients older than 50 years (group 2) received the chemotherapy arm composed of three monthly consolidation courses (DNR or ZRB, cytarabine, and asparaginase) followed by maintenance chemotherapy (modified L10 regimen). The remaining population (group 3) was randomly assigned to receive, after the three 1-month consolidation courses, either the chemotherapy arm or autologous BMT following a conditioning regimen similar to that of group 1. RESULTS: Of the 572 assessable patients, 436 achieved complete remission (78% +/- 2% for DNR v 74% +/- 3% for ZRB; P = .3). The estimated 3-year disease-free survival (DFS) rate for the 116 patients included in group 1 was 43% +/- 5%. Both autologous BMT (95 patients) and chemotherapy (96 patients) produced comparable 3-year DFS rates (39% +/- 5% v 32% +/- 5%) and survival durations (49% +/- 5% v 42% +/- 5%). However, late relapses after 36 months were mainly observed in the chemotherapy arm. CONCLUSION: This first interim analysis did not demonstrate a benefit of this autologous BMT procedure over classical maintenance chemotherapy in patients with ALL who received consolidation chemotherapy.
Autologous blood stem cell transplantation (ASCT) was performed in 32 patients with high risk chronic myelogenous leukemia (CML). Prior to ASCT, the patients were given Busulfan and high-dose Melphalan. Peripheral blood stem cells collected at diagnosis were used to rescue hematopoiesis. Recombinant Interferon was administered after ASCT. In 24 patients transplanted in transformation, 23 achieved a complete hematological response and nine are still alive 9 to 73 months after ASCT. Eight other patients were transplanted in chronic phase for either the presence of bad prognostic factors (Sokal's classification) or no response to IFN. Seven are alive without transformation 16 to 48 months after ASCT. Although few patients presented a cytogenetical response (10/28), the survival observed in this series of patients compares favorably with that of patients treated conventionally. Thus, the place of ASCT in CML could now be tested prospectively.
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Two different molecular techniques were used to monitor chimerism following 17 non-T cell-depleted BMTs from female donors to male recipients: pHY10, a Y chromosome-specific probe (Southern or slot blots), and a set of primers for Y chromosome sequence-specific amplification by the polymerase chain reaction (PCR). On Southern blots, male DNA was detectable at a level less than 1% of 10 micrograms DNA while cross-reactivity with autosomal sequences was avoided. On slot blots, male DNA was reliably detectable at levels less than 0.5%, even in small sample (0.5 microgram DNA). With the PCR technique, male DNA was detectable at levels of 1:10(6) to 1:10(7) of 0.5 microgram DNA. Slot blot and PCR results were concordant in 19 of 23 samples. Both techniques demonstrated a constant small mixed chimerism during the first year after BMT and in four of nine patients, this chimerism persisted even longer (up to 29 months after BMT).
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Long term and semi-solid culture techniques were used to evaluate the quality of stroma produced by bone marrow from 33 normal subjects and 57 patients (46 allogeneic bone marrow and 11 autologous blood stem cell transplant recipients). Bone marrow from transplant recipients was capable of sustained CFU-GM and nucleated cell production in long term culture. However, only 13% of the marrow investigated developed a complete, confluent stromal layer. These stromal abnormalities were observed in spite of complete hematopoietic reconstitution after transplantation and rarely improved with time. Our results suggest that the hematopoietic microenvironment is very fragile and susceptible to long term damage as a result of chemotherapy and the conditioning regimes used prior to transplantation.
Serial marrow karyotyping was performed in 31 chronic myeloid leukemia (CML) patients treated with allogeneic bone marrow transplantation (BMT). Of 11 hematological relapses, seven were heralded for up to 20 months by a cytogenetic relapse (characterized by increasing percentages of Philadelphia (Ph)-positive metaphases, seen on serial karyotypes). Chromosomal abnormalities additional to the Ph, seen before BMT, were not found again at relapse. Relapses were characterized by clonal evolutions of the Ph-positive cells, likely corresponding to cytogenetic patterns of treatment-induced leukemia [del(5q), del(7q), complex karyotypes] and were different from those generally found in CML evolution. Involvement of chromosome 1 was also frequent. Sporadic Ph-positive metaphases (not seen in repeated karyotypes) were seen only during the first 8 months after BMT.
Fifteen chronic myelocytic leukemia patients in durable complete cytogenetic conversion (CCC) under interferon therapy, were monitored every three to six months by bone marrow (BM) karyotypes and/or reverse-transcription polymerase chain reaction (RT-PCR) on peripheral blood (PB) leukocytes (by a nested primer approach using two rounds of amplification, 30 cycles each). Special care was taken to minimize the risk of contamination. The median time of follow-up after first CCC was 12 months (range, 6-30). Thirty five BM karyotypes were performed. Only three patients demonstrated the transient reappearance of a few Philadelphia-positive metaphases, while other patients remained in CCC. Forty five PB samples were studied by RT-PCR. In two patients, no BCR/ABL transcript could be detected in three consecutive samples. In the 13 other cases, RT-PCR was intermittently negative, indicating a level of residual leukemic cells close to the threshold of sensitivity of the technique.
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In order to compare the effects of interferon versus hydroxyurea for the treatment of chronic myelogenous leukaemia (CML), 58 CML patients, having received no previous treatment, were randomized into two treatment groups (hydroxyurea or interferon) for an open multicentre study from 1 May 1987 until 1 July 1990. Fifty patients were evaluable: 24 in the interferon group and 26 in the hydroxyurea group. Haematological response was obtained in 16/24 interferon-treated patients and 23/26 hydroxyurea patients. Failure to obtain haematological remissions occurred in eight of 24 interferon-treated patients and in three of 26 hydroxyurea patients. Four interferon-treated patient failures and one hydroxyurea-treated failure were due to drug intolerance. Progression occurred in one interferon-treated patient and in three patients given hydroxyurea. Fourteen of 16 patients in the interferon group and 17/23 in the hydroxyurea group continue on study and show no progression.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.