Successful pregnancy following allogeneic bone marrow transplantation after conditioning by thoraco-abdominal irradiation.

A 26-year-old woman delivered a normal child 5 years after bone marrow transplantation for severe aplastic anemia. The conditioning regimen comprised high dose cyclophosphamide and thoraco-abdominal irradiation (6 Gy). This and two previous cases demonstrate that normal pregnancy can follow total body or thoracoabdominal irradiation.

Cell-cycle prognostic value in adult acute myeloid leukemia. The choice of the best variables.

Flow cytometry with simultaneous analysis of DNA and protein content allows a most exhaustive study of cell-cycle for the prognostic evaluation of acute myeloid leukemia (AML). Sixty-seven cases of AML were studied before any form of chemotherapy had been undertaken. We determined the following cell-cycle variables: S, S + G2 + M, low protein content fraction (LPC-fraction) and high protein content fraction of G1 (HPC-G1). Patients were stratified according to age: S and S + G2 + M phases were higher for patients over 50 who did not achieve a complete remission. LPC-fraction was significantly lower for patients older than 50 who did not achieve a complete remission not only compared to the complete remission group of patients over 50, but also compared to the younger non responder group. The duration of survival was significantly longer when LPC-fraction was higher than 26% and HPC-G1 lower than 70%. Length of survival was also better when S + G2 + M was longer than 5.75%. Analysis of the therapy failure showed that S + G2 + M and LPC-fraction were significantly different between the complete remission group and the group of patients dying in aplasia. Overall, patients older than 50 with a proliferative leukemia had a worse prognosis.

Cell-cycle, protein content, and nuclear size in acute myeloid leukemia.

Simultaneous analysis of DNA and cellular proteins provides information on cell proliferation and metabolism. Cellular protein content coupled with nuclear geometric parameters can be used to evaluate cellular maturation and differentiation. In this study, leucoblasts from 50 cases of adult acute myeloid leukemia were analyzed by flow cytometry, and semiautomatic morphometry was performed on bone marrow smears. Ethanol-fixed bone marrow blast cells were stained for DNA with propidium iodide (PI) and for proteins with fluorescein isothiocyanate (FITC). On the resulting FITC versus PI histograms we defined the cells with low protein content which are associated with a nonproliferating subpopulation (LPC fraction). Low protein content fraction and S-phase are correlated (p less than 0.01). The LPC fraction values are more dispersed than S-phase values and thus should indicate more clearly eventual differences between cellular populations. This hypothesis has been tested with the prognostic significance of cell-cycle variables: The LPC fraction was significantly higher in the complete remission group than in the other (p less than 0.01), while S-phase did not show any difference. The peak value of the protein content histograms is significantly lower in the granulocytic leukemias (M1, M2, M3) than in the leukemias with a monoblastic component (M4, M5). Furthermore, we showed that the differentiation and the maturation of the myeloid blast cells modify the nuclear size. The combination of these two parameters provides useful information for cytological classification.

Transplant of rhesus-positive bone marrow in a rhesus-negative woman having anti-rhesus D alloantibodies.

A woman affected by acute myeloblastic leukemia was grafted with HLA A, B and D compatible rhesus-positive bone marrow from her brother. Before grafting, she had anti-D alloantibodies (1/512 IAT, 2.9 micrograms/ml). To prevent the destruction of donor red blood cells, four plasma exchanges and a conditioning regimen (total-body irradiation 800 rad, cyclophosphamide, methotrexate) were carried out to decrease anti-D from 2.9 to less than 0.02 micrograms/ml on day 0. The anti-D level was 0.8 micrograms/ml on day 12 and was decreased to 0.2 micrograms/ml by eight plasma exchanges until day 35. Anti-D antibodies were undetectable with Lalezari's technique on day 45. Engraftment was obtained on day 25 (3,000 leukocytes/mm3 and 50% erythroblasts in bone marrow). The patient died from aspergillosis and graft-versus-host disease on day 54. This observation shows that an engraftment of rhesus-positive bone marrow in a recipient with anti-D antibody is possible.

Remission of acquired pure red cell aplasia following plasma exchanges.

A 22-year-old woman had an idiopathic pure red cell aplasia that failed to respond to high doses of corticosteroids. After a series of 10 plasma exchange procedures, bone marrow erythropoiesis and reticulocyte blood count returned to normal; the haematological remission has been now persistent for 12 months. The place of plasma exchange in the management of pure red cell aplasia and its mode of action will be discussed.

[Ineffective cortico-sensitive erythropoiesis in 2 young adults]. / Erythropoïèse inefficace cortico-sensible chez deux adultes jeunes.

A 21 year-old man and a 17 year-old woman presented with severe anemia of unknown etiology. The bone marrow aspiration showed many erythroblasts which were morphologically normal, but there was no reticulocytosis; the 59Fe kinetics were typical of a major ineffective erythropoiesis. A rapid and total improvement occurred following steroid treatment. In the first case, there was a transient and cortico-responsive thrombocytopenia before and after the anemia and in the second case, the antiglobulin test was sometimes weakly positive. An immunological disturbance against the late erythroblasts is likely. Perhaps these case are not very different from those reported as "hemolytic anemia with reticulocytopenia".

Serum beta 2 microglobulin in adult myeloid acute leukemias.

Serum beta 2 microglobulin levels, measured by radioimmunoassay (Phadebas test), were found increased in acute myeloid leukemias at diagnosis. Serum beta 2 microglobulin levels were significantly higher in patients with monocytic leukemias (13 patients, M4-M5 FAB classification) than in those with other cytological types (18 patients). Beta 2 microglobulin levels at diagnosis were correlated with serum lysozyme levels, but they were not correlated with blood blast counts, serum LDH and ferritin levels. 195 serum beta 2 microglobulin measurements were made serially in 30 patients with acute myeloid leukemias in first remission. Compared to values at diagnosis, beta 2 microglobulin levels in remission were significantly decreased. Out of 30 patients in remission 12 had increased serum beta 2 microglobulin levels (greater than 3 mg/l). Serial measurements were not predictive for relapses.

Serum levels of ketoconazole in bone marrow transplanted patients.

Seven patients with acute leukemia were treated by allogenic bone marrow transplantation from HLA matched sibling. The conditioning regimen was classical using cyclophosphamide and Total Body Irradiation, followed by methotrexate. All patients were given ketoconazole (400 mg per day in a single dose) as antifungal prophylaxis for 6 months. Serum ketoconazole levels were measured using the inhibition assay of mycotic culture in gelose, and they were studied at 0, 1, 2, 4 and 6 h after ketoconazole ingestion, and repeated serially after bone marrow transplantation. In these transplanted patients, absorption of ketoconazole could be delayed, with the maximum levels at 4 h or 6 h after ingestion. Most measurements showed appropriate levels (maximum levels greater than 1 mg/l) even after the third week post transplantation. With the exception of severe acute GVH disease (1 patient), the ketoconazole absorption was adequate in minor or mild GVH disease (6 patients) and in chronic GVH disease (2 patients). In four patients ketoconazole absorption was compared with gut absorption tests (Schilling's test, Iron absorption test, xylose test): In all patients the maximum serum levels of ketoconazole were correct, even in three patients with abnormal gut absorption tests. In this series, no life-threatening mycotic infection occurred, and the three deaths observed showed no mycotic infection.

[Prolonged survival in adults with acute myeloid leukemia treated with BCG immunotherapy]. / Longue survie dans les leucémies aiguës myéloïdes de l'adulte sous immunothérapie par le B.C.G.

Between november, 1974 and june, 1977, 64 adult patients with acute myeloid leukaemia in remission were divided at random into two treatment groups: chemotherapy alone (n = 32) or chemotherapy plus B.C.G. (n = 32). Fresh B.C.G. from the Pasteur Institute, Paris, was administered once a week, two or three times per month, in the intervals between chemotherapy cycles, using the Heaf-gun method. The duration of the first remission was significantly increased in the group receiving B.C.G. (median duration 685 days versus 390 days: p = 0.03 on log rank test) as was the overall survival (median duration of survival 1.471 days versus 554 days: p = 0.01). Second remissions were more frequent in the B.C.G. group (79% versus 42%; p = 0.014). In addition, prolonged survival was more frequent in the B.C.G. group, where 12/32 patients remained in first remission between 3 and 6 years, as against 5/32 in the chemotherapy group.

Agar culture of bone marrow cells in acute myeloid leukemia and dysmyelopoietic syndromes. Reevaluation of its prognostic value.

The expression of results obtained in in vitro bone marrow cell culture as per ml of aspirated marrow instead of per 10(5) nucleated cells plated as studied in 41 patients with acute myeloid leukemia (AML) and 79 patients with a dysmyelopoietic syndrome. Four types of growth were found in AML patients: three with hypercellular marrow and either (a) microclusters, (b) isolated cells, or (c) macroclusters and a complete remission (CR) rate of 86%, 63%, and 14% respectively; (d) relative hypocellular marrow with a CR rate of 0%. This type of poorly responsive AML patient has recently been described [17]. Patients with dysmyelopoietic syndromes were subdivided into three groups according to th type of in vitro growth: subnormal, decreased, and leukemic. There was a good correlation between these in vitro groups and the outcome of patients: long survival, death from hemorrhagic and/or infectious complications, leukemic transformation (logrank test: chi 2 = 9.12, df = 2, p = 0.01).

[Autologous haematopoietic stem cell transplantation. Preliminary results of a regional multicentric study (author's transl)]. / Greffe de cellules-souches hématopoïétiques autologues. Premiers résultats d'un protocole régional (author's transl)]

Autologous bone marrow transplantation represents a new approach to the treatment of malignant diseases when conventional therapy has failed. For this reason, the authors have collected bone marrow from 46 patients, including 24 with acute leukaemia, 7 with chronic myeloid leukaemia, 10 with lymphosarcoma and 5 with solid tumours. The mean of total cryopreserved CFU-c was 8.5 X 10(6) (range: 0.2-25). Ten cases of autologous bone marrow transplantation are reported. Seven patients had been prepared with high dosage chemotherapy alone (TACC) and three with chemotherapy combined with total body irradiation. Haematopoiesis restarted within 9 to 15 days in 5 patients and within 22 to 34 days in the other 5. Complete remission was obtained in all 5 patients with acute myeloid leukaemia grafted during their first relapse, the longest remission up to now being 390 days. One patient with chronic granulocytic leukaemia is still in second chronic phase after 360 days. Stem cells were transplanted early in the course of a T-lymphosarcoma, during complete remission; maintenance chemotherapy was withdrawn, and the chances of success of this treatment alone are being evaluated. The kinetics of blood and bone marrow CFU-c populations after transplantation were studied in 4 cases and were found to correlate closely with haematopoietic recovery following ablative bone marrow therapy. Stem cell transplantation can only be justified in acute leukaemia if it is carried out immediately after complete remission to consolidate the results and, hopefully, to prolong the remission.

Chronic granulocytic leukemia : early detection of metamorphosis with "in vitro" culture of granulocytic progenitors.

The study of bone marrow granulocytic precursors (GM CFU-C) has been made in patients with a chronic granulocytic leukemia (CGL), at diagnosis and during the evolution. In vitro growth was increased with a normal clusters/colonies ratio in 17 patients, 2 have presented a metamorphosis. In vitro growth was abnormal in 30 patients, 22 have presented a metamorphosis with a median of 9 months after the in vitro study. The in vitro growth of GM CFU-C in CGL patients could detect the metamorphosis.

[Treatment of 100 acute myeloid leukemias (author's transl)]. / Traitement de cent leucémies myéloides aigues.

Between november 1974 and august 1976, 100 acute myeloïd leukemias were treated by the same protocol L. 275. Induction treatment was daunorubicine, vincristine, cytosine arabinoside, in one intensive course for patients under 65 and cyclophosphamide (CPM), VCR and CAR in a less intensive and repetitive courses for patients over 65. In remission, there were three phases: consolidation, prevention of central nervous system leukemia, maintenance. All patients in remission received an androgenotherapy and two groups were randomised: chemotherapy and chemotherapy plus BCG. 68 patients were in complet remission (CR) 61 out of 80 patients under 65 and 7 out of 20 over 65. Median duration of first remission was 12 months. Median duration of survival was 13 months for all patients, 15 months for patients under 65, 3 months for patients over 65, and 22 months for 68 patients in CR. Survival of patients receiving BCG was slightly better than patients without BCG.

[Prognostic value of delayed-hypersensitivity skin tests and rosette studies in acute non-lymphoid leukemias]. / Valeur pronostique des réactions cutanées d'hypersensibilité retardée et de l'étude des rosettes dans les leucémies aiguës non lymphoïdes.

Delayed hypersensitivity skin reactions to Tuberculin and Candidin were studied in 28 patients with non lymphoid acute leukemias. The reactions were found negative in most patients during blastic crises, whereas delayed skin reactions to Candidin were positive during remissions. The possible prognostic significance of the depressed delayed hypersensitivity response in such patients deserves further studies. Alterations of circulating T lymphocytes were observed, including low percentages of E and active E rosette-forming cells during blastic crises, and persisting low E and E active rosettes in some patients in remission; such abnormalities were less frequent in patients with remission of long duration. The percentages of EA and EAC rosettes-forming cells were found normal during blastic crises and remissions. In some patients in remission, lymphocytes were found to bind sheep erythrocytes either uncoated or coated with IgM antibodies, this penomenon which is not observed with normal lymphocytes may reveal persisting abnormalities of a yet undefined nature.

Immunoglobulin deposits and testis tubular membrane pathology in human sterility.

Immunoglobulin deposits were detected by IF technique on tubular membranes of sterile patients' testicular biopsies (40%). Positive staining was correlated with high-grade tubular membrane damages (15 over 23 M3, M4, M5 sections were positive, against 0 over 5 M0 sections).