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Biomedical subjects

N Milpied

Publications and source records attributed to N Milpied.

At least 163 records · Page 9Linked to original sources
PubMed1991

Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG.

Allogeneic bone marrow transplantation (BMT) was performed in 17 patients with chronic lymphocytic leukemia (CLL): 15 resistant and two untreated forms. There were 12 males and five females with a mean age of 40 years (32-49). The conditioning regimens and graft-versus-host disease (GVHD) prophylaxis varied. Successful engraftment was obtained in 15 evaluable cases. Lymphocytosis and clinical symptoms subsided in all but one case. All 15 evaluable patients developed acute GVHD. Among the 17 patients grafted, one early death was observed at the 15th day post-BMT, and one refractory patient died 2 months after BMT. Of the remaining 15 patients in complete remission (CR), four died from GVHD, hemorrhage and graft failure, and two relapsed at 7 and 54 months after BMT and died. Nine patients are alive in CR with a mean follow-up of 25.6 months (4-48). Chimerism was complete in eight patients and partial in the two T cell-depleted cases. In one case, an immunoglobulin gene rearrangement study showed no residual disease. These results suggest that allogenic BMT might be an alternative and possible curative therapy for refractory CLL in young patients when performed relatively early in the disease.

Adult↗
PubMed1990

Successful treatment of adult acute lymphoblastic leukemia after relapse with prednisone, intermediate-dose cytarabine, mitoxantrone, and etoposide (PAME) chemotherapy.

Thirty-nine patients with relapsed acute lymphoblastic leukemia (ALL) and four with primarily refractory ALL were treated with a regimen that included cytarabine 1 gm/m2 (2-hour infusion) twice daily days 1 to 5, mitoxantrone 12mg/m2 daily days 1 to 5, prednisone 0.5 mg/kg daily days 1 to 5, and etoposide 200 mg/m2/day daily days 6 to 8. Of the 43 patients, 30 achieved a complete remission (CR), 28 out of the 39 relapsed patients and two among the four with refractory disease. Five patients died in aplasia. Eight patients were nonresponders. Nonhematologic side effects consisted predominantly of nausea, vomiting, and mucositis. One patient had transient cerebellar dysfunction. Recovery of blood counts occurred at a median of 24 days. The median time to CR was 38 days. As this regimen is highly effective in relapsed or refractory ALL, its use during earlier stage of the disease is warranted.

Adolescent↗
PubMed1990

Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10)

In a multicenter pilot study, 32 patients showing steroid-resistant acute graft-versus-host disease (GVHD) were treated by in vivo administration of anti-interleukin-2 (IL-2) receptor monoclonal antibody (MoAb B-B10). Twenty-three patients received marrow from HLA-matched related donors, four from matched unrelated donors and five from partially matched related donors. The overall grade of GVHD was II in 16 patients, III in two, and IV in five. Five milligrams of B-B10 MoAb was infused in bolus daily for 10 days and then every second day for a further 10 days in an attempt to reduce GVHD recurrence. No clinical side effects were noted during the B-B10 treatment period. A complete response (CR) acute GVHD was achieved in 21 patients (65.6%). Six patients (18.7%) showed partial improvement (PR) and 5 patients (15.6%) no response (NR). A significant factor associated with GVHD response was the delay between the onset of the GVHD and the first day of B-B10 infusion. The earlier B-B10 was introduced, the greater the probability of CR (P = .03). There was no correlation between the serum B-B10 level and GVHD response (P = .69). There was, however, a significant correlation between the clinical response and the B-B10 kinetics as a function of time: serum B-B10 levels attained a plateau level more rapidly in the CR group than in the PR/NR group. Among the 26 complete and partial evaluable responders, GVHD recurred in 10 cases (38.4%). Host anti-B-B10 MoAb immune response occurred in only one (7.1%) of the 14 patients analyzed. Fourteen of the 32 patients (43.7%) are currently alive between 2 and 14 months after GVHD treatment with B-B10 was completed.

Adolescent↗
PubMed1990

Allogeneic bone marrow transplantation in adults with Burkitt's lymphoma or acute lymphoblastic leukemia in first complete remission.

The prognosis of adults with Burkitt's lymphoma is very poor and depends on initial CNS and/or bone marrow involvement. We report results in nine adult patients with CNS (n = 9) and/or bone marrow involvement (n = 7) treated in first complete remission (CR) with allogeneic bone marrow transplantation (BMT). CNS treatment before the conditioning regimen consisted of cranial irradiation at 15 Gy (n = 8) and intrathecal chemotherapy (n = 9). The conditioning regimen included cyclophosphamide and total body irradiation (TBI) in a single dose. No postgraft CNS prophylaxis was administered. At the present time, seven patients are alive and disease-free at 18, 23, 44, 47, 54, 54, and 59 months. Two patients died at 14 and 7 months from transfusion-related acquired immune deficiency syndrome and bacterial septicemia and were disease-free at the time of their death. These preliminary results should encourage the use of BMT. A prospective randomized trial is warranted to further specify and investigate the advantages of allogeneic BMT versus conventional chemotherapy.

Adolescent↗
PubMed1990

Influence of HLA-DP mismatches on primary MLR responses in unrelated HLA-A, B, DR, DQ, Dw identical pairs in allogeneic bone marrow transplantation.

The success of bone marrow transplantation relies on class I and class II HLA identity between donor and recipient but until now the impact of DP mismatches on primary mixed lymphocyte reaction (MLR I) responses has not yet been clearly established. HLA-DP typing has been performed by a RFLP method on 10 patients and their 22 selected potential donors (HLA-A, B, DR, DQ, Dw identical according to serological, RFLP and oligotyping methods). HLA-DP-matching was then correlated with MLR I responses obtained (1) in 22 HLA-A, B, DR, DQ, Dw identical donor-recipient pairs (patient series) and (2) in 30 HLA-A, B, DR, DQ, Dw identical donors pairs used as the control series. We showed that MLR I responses involving patients cells were always lower than those involving control cells (p less than 0.02 in case of two DP-mismatches and p less than 0.001 in the case of one DP-mismatch). Moreover, in the control series two or one DP mismatches influenced MLR I responses in 91% and 77% of the cases respectively; however, there was a greater scatter of response values which could be explained by the degree of sequence homology between the DP mismatched alleles. In cases with no DP mismatch, no proliferative response was observed. Overall, these results suggest that the conventional technical conditions of MLR I do not allow detection of mismatches other than the well known HLA specificities.

Bone Marrow Transplantation↗
PubMed1990

Long-term follow-up after bone marrow transplantation for chronic myelogenous leukemia: factors associated with relapse.

Data on 281 patients with chronic myelogenous leukemia who received bone marrow transplants were analysed. The median follow-up time was 40 months; 170 patients were in first chronic phase, 14 were in second chronic phase, 73 were in accelerated phase and 24 were in blastic crisis. The overall actuarial survival was 50% at 5 years. In multivariate analyses, the probability of relapse correlated with the phase of the disease, the method of total body irradiation, the T cell depletion of the marrow and the occurrence of a chronic graft-versus-host disease (GVHD). The probability of survival was better for patients with grade 0-1 GVHD than for patients with grade 2-4 GVHD. In contrast, the probability of disease-free survival was significantly better for patients who received a non-T cell-depleted marrow than for recipients of T cell-depleted marrow. Interval between diagnosis and transplant, splenectomy before transplant, patient age and donor recipient sex match were not significantly associated with outcome. Bone marrow transplantation in first chronic phase with an HLA identical non-T cell depleted marrow offers the better chance of prolonged leukemia-free survival.

Adult↗
PubMed1990

Mitoxantrone and intermediate-dose cytarabine in relapsed or refractory acute myeloblastic leukemia.

In order to reduce the incidence of severe complications noted with regimens containing high-dose cytarabine (HD ARA-C), wer used a combination of mitoxantrone (MTZ) in optimal dosage (12 mg/m2/day for 5 days) and cytarabine in intermediate dosage (1 g/m2 twice daily for 3 or 5 days). Thirty patients aged 2 to 65 years (median 51) with acute myeloid leukemia (AML), either refractory (8 patients), in first relapse (20 patients) or chemoinduced (2 patients), received this program. Seventeen (57%) achieved complete remission (CR). The main prognostic factor was the previous use of HD ARA-C (21% CR for patients previously treated with HD ARA-C versus 87% for patients treated with conventional doses: P less than 0.001). Mucositis was the most significant extrahematologic side-effect. There was no severe cerebellar toxicity. Two patients had transient congestive cardiac failure. This regimen is effective and relatively well tolerated in heavily pretreated patients. It can be used either as induction or consolidation therapy in AML.

Adolescent↗
PubMed1990

Bone marrow transplantation for chronic myelogenous leukemia. Results of the French Cooperative Group (GEGMO).

Data on 281 patients with chronic myelogenous leukemia who received bone marrow transplants were analyzed. The median follow-up time was 48 months. One hundred and seventy patients were in 1st chronic phase, 111 were in more advanced disease. The overall actuarial survival was 50% at 5 years. In multivariate analyses, the probability of relapse was correlated with the phase of the disease, the method of total body irradiation, the T cell depletion of the marrow and the occurrence of a chronic GVHD. The probability of disease free survival was significantly better for the patients who received a non T cell depleted marrow than for recipients of T cell depleted marrow. Bone marrow transplantion in first chronic phase with an HLA identical non T cell depleted marrow offers the better chance of prolonged leukemia free survival.

Acute Disease↗
PubMed1990

Collagen gel cultures for detection of spared hematopoietic progenitors in Asta Z 7557 purged human marrows.

Asta-Z 7557, an in vitro active metabolite of cyclophosphamide, is used for human bone marrow purging in acute leukemias and solid tumors since it is more highly toxic to tumor than normal hematopoietic clonogenic cells. However, doses higher than 80 microM totally inhibit the growth of hematopoietic progenitors in semisolid assays, despite preservation of marrow repopulating ability in vivo. This discrepancy complicates assessment of the functional value of purged grafts. In 11 patients undergoing autologous bone marrow transplantation with 100 microM Asta-Z purged marrow, we investigated the advantages of the collagen gel culture system for detection of spared hematopoietic progenitors. This technique provides a suitable and convenient assay as compared with results with agar. In nine of 11 samples after 14 or 21 days of incubation, up to 100 colonies were observed, (64% monocytic, 27% granulocytic). Day-14 granulocytic colonies were mostly immature, suggesting that they derived from early CFU-GM or pre-CFU-GM. This development of early progenitors could account for the better sensitivity of this technique compared with agar or methylcellulose systems. The mechanism involved as well as the correlation between colony growth in collagen and clinical hematopoietic recovery is also considered.

Adolescent↗
PubMed1989

Bone marrow transplantation for adult poor prognosis lymphoblastic lymphoma in first complete remission.

Twenty-five adult patients, 19 males, six females, age 16-43 years (median 23), with lymphoblastic lymphoma received allogeneic or autologous bone marrow transplantation in first complete remission. Twelve patients were Murphy stage IV with bone marrow and/or CNS involvement and 13 were stage III of whom nine had thoracic involvement. Complete remission was achieved with an intensive anthracycline containing multiagent chemotherapy protocol. Twelve patients with an HLA identical sibling received an allogeneic marrow and 13 without a donor received their own marrow harvested a median of 2 months (0-4 months) after complete remission and purged in vitro with either mafosfamide (eight patients) or anti T-cell monoclonal antibodies and complement (three patients). Bone marrow transplantation was performed 1-7 months (median 3 months) after achieving first complete remission. The conditioning regimen consisted of cyclophosphamide or high dose melphalan and total body irradiation. The actuarial 4-year disease-free survival is 68% (+/- 9% SE). The actuarial probability of relapse was 26% (+/- 3% SE) with a median follow up to 22 months. There was no difference between allogeneic and autologous transplantation with eight out of 12 allo patients in first continuous complete remission 26-45 months after transplant and nine out of 13 auto in continuous complete remission 15-75 months after transplant. These results compare favourably with those achieved with the best chemotherapeutic regimen used for such patients.

Adolescent↗
PubMed1989

Treatment of acute myeloid leukemia in elderly patients with oral idarubicin as a single agent.

Idarubicin (IDR) is a new anthracycline that can be administered orally. Oral IDR was given at a dose of 30 mg/m2 daily for 3 d in 20 patients aged 65 to 79 yr with previously untreated acute myeloid leukemia (AML). 5 patients whose marrow remained blastic at d 14 received a second course. 8 patients achieved complete remission (6 after one single course). There were: 1 early death, 4 deaths in aplasia, 7 failures. The hematologic toxicity was high. All but 1 patient had to stay in hospital and the duration of neutropenia was 12 to 34 d (median 19). Oral IDR is an effective therapy for AML in elderly patients but the total dose of 90 mg/m2 is too aggressive to be administered safely outside the hospital.

Administration, Oral↗
PubMed1989

Treatment of relapsed acute myeloid leukemia with idarubicin and intermediate-dose cytarabine.

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.

Adult↗
PubMed1989

Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia in first remission: a cooperative study of the Groupe d'Etude de la Greffe de Moelle Osseuse.

Thirty-two children ranging in age from 1.5 to 16 years with poor-prognosis acute lymphoblastic leukemia (ALL) were treated with myeloablative immunosuppressive therapy consisting of cyclophosphamide (CPM) and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) while in first complete remission (CR). The main reasons for assignment to BMT were WBC count greater than 100,000/microL, structural chromosomal abnormalities, and resistance to initial induction therapy. All children were transplanted with marrow from histocompatible siblings. Twenty-seven patients are alive in first CR for 7 to 82 months post-transplantation (median, 30 months). The actuarial disease-free survival rate is 84.4% (confidence interval, 7.2% to 29%) and the actuarial relapse rate is 3.5% (confidence interval, 0.9% to 13%). Four patients died of transplant-related complications, 16 developed low-grade acute graft-v-host disease (GVHD), and six developed chronic GVHD. The very low incidence of relapse (one of 28 long-term survivors) precluded the determination of the prognostic significance of the different poor-outcome features. Moreover, two infants treated with busulfan, CPM, and cytarabine (Ara-C) relapsed promptly in the marrow. In summary, as a means of providing long-term disease-free survival and possible cure, BMT should be considered for children with ALL presenting poor-prognostic features, particularly certain chromosomal translocations [t(4;11), t(9;22)], very high WBC counts, notably if associated with a non-T immunophenotype, and, perhaps, a poor response to initial therapy with corticosteroids (CS), or infants less than 6 months of age.

Adolescent↗