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EMA 86 regimen, associating mitoxantrone, 12 mg/m2/day on days 1–3, etoposide, 200 mg/m2/day as a continuous infusion on days 8–10 and cytarabine, 500 mg/m2/day as a continuous infusion on days 1–3 and 8–10, was administered to 133 patients. 70 patients had refractory AML and 63 had late first relapse. 60% achieved complete remission (CR), including 44% of refractory patients and 76% late first relapse patients (p = 0.0002). 11% died from therapy-related toxicity. Median survival is 7 months, with 11% survival at 5 years. Median disease-free survival (DFS) is 8 months, with 20% DFS at 5 years.

Expression of CD56 was analyzed by indirect immunofluorescence method on bone marrow samples from 94 newly diagnosed patients with acute leukemia (AL), including 59 acute myelogenous leukemias (AML) and 35 acute lymphoblastic leukemias (ALL). CD56 was expressed on 17 +/- 18% (range: 0-72%) of AML cells and 24 +/- 24% (range: 0-98%) of ALL cells, without significant differences between FAB subtypes in AML, nor immunologic subtypes in ALL. Expression of CD56 was not associated with any clinical or biological characteristic at diagnosis, nor with prognosis in AML or ALL. We do not confirm previously described relationships between CD56 expression and initial characteristics and evolution of acute leukemia.

We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course (“4 + 7” course), then three “2 + 5” DNR + Ara C courses and maintenance chemotheapy. However, the “4 + 7” course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the “4 + 7” course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the “4 + 7” course. Four patients did not receive this course but received the subsequent “2 + 5” courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Two clones were observed at the initial phase of an acute myelogenous leukemia (AML): 46,XX,t(15;17) and 46,XX,t(8;21),t(15;17). Clinical, immunologic, and morphologic findings were in favor of expression of both chromosomal anomalies. Relapse occurred after 12 months of complete remission with typical acute promyelocytic leukemia (APL) syndrome when t(15;17) alone was then most predominant.

Anaphylactoid reaction to cyclophosphamide administration in a 85-year old woman is described. Symptomatology was restricted to bronchospasm, which regressed within one hour. This incomplete and rapidly regressive symptomatology might be explained by previous administration of methylprednisolone. No anaphylactoid symptoms were observed following continuation of therapy with ifosfamide.

We performed molecular cloning and sequencing of the breakpoints of a new chromosomal translocation involving the MYC protooncogene locus. This secondary t(8; 12)(q24;q22) was associated with a primary t( I I; 14)(q I 3;q32) translocation in a case of B-cell chronic lymphocytic leukemia (CLL) in blastic transformation. In this leukemia, Northern blot and nuclease analyses SI showed that MYC was strongly expressed with initiation of the transcription at both the 5′ and 3′ promoters as observed in Burkitt's lymphomas; no coding change was observed in MYC putative regulatory sequences. The breakpoint on chromosome 8 mapped to the 3′ end of the MYC locus, in a region containing a potential Z-DNA tract, and where we identified two DNase I hypersensitive sites. A rearranged MYC gene fragment was cloned and shown to contain chromosome 12 information by Southern blot analysis and by in situ hybridization. A genomic probe subcloned from the isolated region of the chromosome 12 recognized a 1.8 kb transcript in virtually all the tissues tested but a preferential expression of this new gene, which we termed BTGI (for B-cell translocation gene I) was observed in the CLL cells and in tissues of lymphoid origin. This chromosome 12 coding sequence is conserved in evolution and a transcript of similar size is present in murine tissues.

The addition of high-dose methylprednisolone (120 mg given i.v. and repeated after a 4-h interval) to a conventional antiemetic regimen consisting of metoclopramide (0.5 mg/kg given as an i.v. bolus over 30 min followed by 1 mg/kg given as a continuous infusion over 24 h) and alprazolam (0.5 mg given p.o.) was evaluated in a randomized study of leukemic patients undergoing anthracycline-containing multiple-day chemotherapy. Double-blind analysis was done in 30 patients who completed a total of 40 treatment courses. Cumulative 3-day results revealed complete control of nausea in 66% of patients and complete control of emesis in 77% of cases. The addition of methylprednisolone significantly reduced the occurrence of nausea (p = 0.003) and emesis (P = 0.06). Moreover, antiemetic rescue with chlorpromazine was less frequently necessary in patients receiving corticosteroids (P = 0.02). No harmful side effect was observed, and the incidence of severe infectious episodes was similar in both arms. We conclude that high-dose methylprednisolone can improve the efficacy of metoclopramide and alprazolam in controlling nausea and emesis induced by anthracycline-containing multiple-day chemotherapy in patients with acute myeloblastic leukemia.

To test the value of pefloxacin for the prevention of infections in patients with chemotherapy-induced neutropenia, oral pefloxacin plus vancomycin (PV) (n=76) or gentamicin, colistin sulphate and vancomycin (GCV) (n=74) were administered in a randomised double-blind study. Infections were significantly less severe in the PV than in the GCV group. Patients receiving PV had significantly fewer episodes of bacteraemia and central venous line infections than patients treated with GVC. Gram-positive and gram-negative infections were significantly less frequent in patients receiving PV, because of fewer infections with Staphylococcus species and enterobacteriaceae. Stool culture detected significantly more gram-positive organisms in the PV group and more gram-negative organisms in the GCV group. Thus, PV was more efficacious than GCV for the prevention of gram-positive and gram-negative infections in the neutropenic patients, despite lower efficacy in eradicating gram-positive organisms from the lower intestinal tract.

In order to detect possible relationships between cytogenetic abnormalities and morphologic features in myelodysplastic syndromes (MDS), 48 patients with MDS were investigated. Clonal cytogenetic abnormalities were present in bone marrow cells from 27 patients (56%). The most frequent single anomaly was del (5 q) (10 cases), followed by monosomy 7 (3 cases), trisomy 8 (3 cases) and del (20 q) (2 cases). Complex anomalies were present in 6 patients. Morphologically, according to the French-American-British (FAB) classification: 17 cases were considered as refractory anemia (RA), 17 as RA with excess of blasts (RAEB), 2 as RAEB in transformation, 2 as acquired idiopathic sideroblastic anemia and 10 as chronic myelomonocytic leukemia. With regard to the FAB classification, del (5 q) was often associated with RA and complex cytogenetic anomalies with RAEB. When myelodysplasia was studied in individual myeloid lineages, del (5 q) was associated with hypolobulated megakaryocytes, monosomy 7 with micromegakaryocytes and complex chromosomal anomalies with the association of two or more features of dysmegakaryocytopoiesis. Del (11 q) was associated with increased iron storage and del (20 q) with marked dyserythropoiesis. No correlation was observed between cytogenetic anomalies and features of dysgranulocytopoiesis.

Objective: To characterize in detail the outcomes of HLA-identical sibling bone marrow transplantation for chronic lymphocytic leukemia (CLL) in patients younger than 60 years of age. Design: Retro...

In elderly patients with AML, the induction treatment requires 4–5 weeks of hospitalization. The aim of the phase III AML-13 trial of the EORTC Leukemia Group is to assess two types of consolidation chemotherapy in patients who reach complete remission after the induction cycle : 3 drugs during 7 days, using a classical continuous infusion, on an inpatient basis, or the same kind of drugs but delivered subcutaneously or orally, on an outpatient basis. In the second group, patients are hospitalized only in case of complications. The evaluation parameters are not only disease-free survival and overall survival, but also cost-effectiveness and quality of life. The latter endpoints pose specific methodological challenges. We decided to use a diary to collect information concerning treatment compliance, side-effects of treatment and their impact on quality of life, and use of health care facilities. In addition information concerning resource utilisation during hospital treatment is being collected through the clinical Case Report Forms. This communication aims to discuss the methodological approach to integrate economic and quality of life aspects in this large scale clinical trial.

We report three cases of acute leukaemia with t(4;11) (q21;q23), one of them of undifferentiated and the other two of lymphoid phenotype, occurring after adjuvant radiochemotherapy for breast cancer (two cases) or occupational exposure to radiation (one case). Although the myeloid phenotype and characteristic chromosomal anomalies usually observed in secondary leukaemia were lacking, our observations raise the possibility of causal relationship between exposure to carcinogens and the occurrence of a leukaemia with t(4;11).

In order to identify prognostic factors in angioimmunoblastic lymphadenopathy (AIL), 30 directly diagnosed patients were prospectively followed for more than 42 months. Age and sex distribution, clinical and laboratory findings and evolution were not different from previously reported series. Median duration of survival was 24 months. Parameters associated with a longer survival in our series were localized adenopathies (P = 0.01) and the achievement of a remission (P less than 0.0001). Features associated with a shorter survival included drug exposure in relation to the onset of the disease (P = 0.02), rash (P less than 0.0001), lymph node eosinophilia (P = 0.03) and elevated serum lactic dehydrogenase (P = 0.03). Drug exposure and rash were, however, significantly dependent (P = 0.02). In addition, lymphopenia, the presence of circulating immune complexes, and the absence of polyclonal hypergammaglobulinemia may indicate a poor prognosis, although the significance level is not achieved in this short series. None of the parameters tested was significantly related to the lymphomatous transformation of AIL, which occurred in four cases. It is concluded that multicentric prospective studies of AIL are necessary in order to better define this disorder, to find prognostic factors, and to optimize therapy.

In an attempt to rationalize the use of therapy in acute myeloblastic leukemia (AML) in elderly patients, 69 cases of primary AML in patients older than 60 years of age were reviewed retrospectively. Therapy was empirical and 12 patients received supportive care (SC) only, 35 received aggressive chemotherapy (AC), and 22 received low-dose cytosine arabinoside (LD-araC). Patients receiving SC only often had a poor Karnofski index and their median survival was 17 days. Aggressive chemotherapy yielded complete remissions (CR) in 48% of the patients, whereas 23% of the patients had resistant disease (RD) and 29% had other failures (OF). Low-dose araC, which was administered to patients significantly older than those receiving AC, yielded 23% CR, 68% RD, and 9% OF, with important hematologic toxicity in most patients. Median survival was 211 days in patients receiving AC and 235 days in patients treated with LD-araC. Survival beyond 2 years from diagnosis was noted in the AC group only. A low Karnofski index was the strongest factor in poor prognosis, while age was not a prognostic factor. The initial characteristics of the patients did not allow us to define groups of patients who should be treated by either AC or LD-araC. We concluded that the decision to treat patients actively should rely more on the patient's general condition and socio-economical criteria than on age.

It is known that cigarette smoking induces leukocytosis and increased genetic instability in normal individuals. Therefore, a retrospective review was conducted of 173 patients with chronic myelogenous leukemia to detect a possible influence of cigarette smoking on initial characteristics at the time of presentation and on the course of this disease. Thirty-nine patients (23%) were smoking 5 cigarettes/d or more at time of diagnosis. Cigarette smoking was significantly related to male sex (P = 0.0005) and younger age at diagnosis (P = 0.02) and smokers tended to have lower leukocyte counts (P = 0.07) than nonsmokers. Cigarette smoking was significantly associated with early blast crisis (P less than 0.0001) and short survival (P less than 0.0001). Other characteristics associated with a poor prognosis included hepatomegaly, anemia, and a high percentage of peripheral blast cells at time of diagnosis. When studied in a multivariate analysis, cigarette smoking remained the strongest prognostic factor for both occurrence of blast crisis (P = 0.0003) and overall survival (P = 0.0001). Other poor prognosis factors found in the multivariate analysis included a high percentage of blasts in the peripheral blood at time of diagnosis and high platelet count. It is possible that cigarette smoke may act as a promoter or cocarcinogen in the transformation of chronic myelogenous leukemia.

The clinical significance of surface markers was investigated in 145 cases of acute myeloid (AML) or undifferentiated leukaemia (AUL), using a panel of six monoclonal antibodies directed to NHL-30.5 antigen (expressed on poorly differentiated myeloid cells), CD13, CD14, CD15, CD33 and CD34 antigens. Expression of CD14 was correlated with higher leucocyte count, higher serum lactate dehydrogenase level and presentation with extramedullary disease. There was no strict correlation with the French-American-British classification. However, the expression of CD14 was associated with monocytic subtypes. CD15 was mainly expressed in M2 and M3 subtypes, and NHL-30.5 and CD34 antigens in AUL and M1 leukaemias. All patients were treated with the same intensive induction treatment. Staining by three antibodies had a prognostic value. The complete remission (CR) rates were 38% (26/68) in NHL-30.5-positive versus 75% (62/77) in NHL-30.5-negative cases (P less than 10(-5), 50% (37/74) in CD34-positive versus 72% (51/71) in CD34-negative cases (P = 0.007) and 70% (77/110) in CD15-positive versus 31% (11/35) in CD15-negative cases (P less than 10(-4). Expression of NHL-30.5 and CD34 antigen was associated with shorter survival (P less than 10(-3) and P less than 10(-2) respectively), whereas survival was longer in CD15-positive cases (P less than 10(-3). In multivariate analysis, expression of NHL-30.5 antigen, absence of CD15, and high LDH level were associated with poor survival. CR duration was not influenced by any of the factors studied, including antigen expression. These results suggest that leukaemias with less differentiated phenotype have a lower response rate to induction treatment.

In a companion paper we demonstrated that normal peripheral blood granulocytic precursor cells differentiate after 2-3 weeks in suspension culture. In the studies described here leukemic blast cells obtained from 14 patients with acute myelocytic leukemia (AML) and two patients with chronic myelocytic leukemia in blastic crisis were cultured in McCoy's 5A medium containing 15 per cent fetal bovine serum for 2-3 weeks at 37 degrees C in an atmosphere of 5 per cent CO2-95 per cent room air. 'Spontaneous' myeloid differentiation (20 x 10(4) viable mature myeloid cells ml-1) occurred in the cultures of cells obtained from 8 pts. The differentiation was granulocytic in three cases, monocytic in four cases and of mixed type in one case. Differentiation was independent of the growth of the cells in culture and occurred in four cases after the first week. Monocytic differentiation was seen only in AML of the FAB M4 type whereas granulocytic or mixed differentiation were seen only in AML of the FAB M1 or M2 types. When PHA leucocyte conditioned medium (PHA-LCM) was added to the cultures monocytic/macrophage differentiation was favoured. Inducers of the differentiation of the HL-60 cell line (N-methylacetamide, cytosine arabinoside, or retinoic acid) had no consistent effect on the differentiation and were at times inhibitory. Three patients received therapy with low dose cytosine arabinoside and no correlation was observed between the outcome of the treatment and leukemic cell differentiation in culture in the presence of the drug.

The reactivity of a panel of monoclonal antibodies was studied in fifty-four cases of acute myeloid (AML) or undifferentiated (AUL) leukemias. Thirty-six antibodies from the Myeloid section of the Second Workshop on Human Leukocyte Differentiation Antigens were used in an indirect immunofluorescence assay. The antibodies could be classified into three groups recognizing respectively granulocytic, monocytic or granulomonocytic leukemias. Most antibodies stained erythroblastic and megakaryoblastic leukemias. In each group, it was possible to define antibodies staining either the less differentiated forms (FAB M 1 and M 5 a) or the more differentiated forms (M 2, M 3, M 4 and M 5 b). Six out of eight AUL were stained by some of the antibodies (mainly from the monocytic group). However, a heterogeneity of stainings in a same blast population was observed.

A 69-year-old woman presented with chronic lymphocytic leukemia (CLL) diagnosed after bone marrow recovery following intensive chemotherapy for acute lymphoblastic leukemia. The retrospective diagnosis of initial blastic transformation of CLL was made. The patient eventually died, 5 months after initial blastic phase, from a blastic relapse of her CLL. Immunologic and karyotypic studies of the lymphoid cells at different times during the evolution of the disease provided evidence that both the small lymphocytes and the large blastic cells originated from the same clone since they carried the same surface markers and the same (11;14) (q13;q32) translocation. A subpopulation of cells carried in addition a t(8;12) (q24;q22) together with the loss of the normal chromosome 8 and homozygosity for the abnormal der(8). The possibility that this second population might correspond to the blast cells and that the occurrence of the t(8;12) with homozygosity might be linked to blastic transformation of the CLL is discussed.

A total of 23 patients with high-risk acute myelogenous leukemia (AML) at diagnosis (2 patients), relapsing AML (14) or resistant AML (6) were treated with 25 micrograms/kg i.v. plicamycin every other day for 3 weeks and 500-4,000 mg hydroxyurea per day p. o. according to the WBC count. Aplasia was observed in only two patients. Severe extrahematologic toxicity included sepsis (four cases), vomiting (four patients), toxic hepatitis (three cases), and fibrinopenia (one patient). No partial or complete responses were observed. The 95% confidence interval limit of the overall response rate (CR + PR) was 0-14%.

The diagnostic efficiency of a serum Candida antigen detection test Cand-Tec test) was prospectively investigated in 104 leukemic patients treated by intensive chemotherapy or allogeneic bone marrow transplantation. Candida antigen titers were determined on admission and then weekly as long as patients remained neutropenic. Nine patients had a proven disseminated yeast infection (diagnosed only at autopsy in five cases). The highest Candida antigen titers were 1:2 in two patients and 1:4 or more in seven patients (sensitivity: 76% for this last titer). This highest titer was observed 12 days before to 3 days after the diagnosis. Seven out of the 97 patients without proven deep candidiasis had a maximum titer of 1:4 (specificity: 93%). The positive predictive value was 50% for a titer of 1:4 and 24% for a titer of 1:2, whereas the negative predictive value was 100% for a titer of 1:4 and 97% for a titer of 1:2. Patients with elevated titers were mostly treated by chemotherapy, were older and had a worse prognosis than those with negative titers, although the duration of neutropenia was similar. It is concluded that Candida antigen detection is a reliable method of diagnosis of deep candidiasis in neutropenic patients. The clinical interest in this test, with special regard to empiric antifungal therapy, is discussed.

Glycosyltransferase activities were measured in normal monocytes and in leukaemic monoblasts. Biosynthesis of glycosylated derivatives of dolichyl-monophosphate, which act as intermediates in glycosylation, was measured. Transfer of mannose from GDP-mannose was greatly increased in leukaemic monoblasts. Galactosyltransferase activities, using endogenous protein acceptors, were increased in leukaemic cells of the monocytic lineage compared to normal cells. No significant difference was observed on specific exogenous glycoprotein acceptors. These selective increases of some glycosyltransferase activities in normal and leukaemic monocytic cells can be correlated either with different expression of specific carbohydrate structures or with changes in glycosylation regulation.

A 52-year-old woman presented with angioimmunoblastic lymphadenopathy five years after undergoing enucleation for ocular melanoma. She was first treated by corticotherapy and azathioprine and had two successive remissions over an 18-month period. Lymph node biopsy performed when lymphadenopathy relapsed for the second time showed focal malignant transformation of angioimmunoblastic lymphadenopathy. Intensive polychemotherapy induced a complete remission. Three months after completion of chemotherapy, the patient presented with hepatic metastases from her melanoma and died shortly thereafter. This is believed to be the first documented association between angioimmunoblastic lymphadenopathy and melanoma. Issues regarding the relationship between angioimmunoblastic lymphadenopathy and nonlymphoid malignancies are raised.

In order to establish a method for studying myeloid differentiation, light density, non-adherent, T-cell depleted mononuclear cells prepared from 26 normal peripheral blood buffy-coats were cultured in McCoy'5A medium supplemented with 15 per cent fetal calf serum (FCS) for three weeks at 37 degrees C in a humidified 5 per cent CO2 atmosphere. The total number of viable cells in the cultures on weeks 1 and 2 represented 73 +/- 10 per cent and 98 +/- 41 per cent of the initial number of viable cells seeded. After one week, blasts represented 26 +/- 10 per cent of the initial number of viable cells while all the initially contaminating mature granulocytes had disappeared. After two weeks, granulocytic differentiation was noted in most cultures and viable myelocytes and more mature cells represented 45 +/- 26 per cent of the initial number of viable cells. The differentiation was independent on the lot of FCS used. The addition of PHA stimulated leukocyte conditioned medium to the cultures did not enhance granulocytic differentiation. The granulocytic differentiation observed in the absence of exogenous CSF persisted after removing the cells adhering to the bottom of the flasks on day 2 of the culture. An endogenous colony stimulating activity was detected in the cultures on week 3 but its intensity did not clearly correlate with the degree of granulocytic differentiation.

We report the case of a 70-year-old woman in whom Philadelphia chromosome-positive acute leukaemia occurred 12 years after radiation therapy for a carcinoma of the cervix. Morphology of the blasts was undifferentiated and immunological studies were in favour of a CALLA-positive acute lymphoblastic leukaemia. A possible relationship between the onset of leukaemia and the former radiation therapy is suggested.

A case of acute leukaemia following intensive chemo- and radiotherapy for solid tumour is reported. A 15-year-old girl received four courses of chemotherapy with adriamycin, cyclophosphamide and cisplatinum after the surgical diagnosis of ovarian immature teratoma. An intensification treatment was performed with cyclophosphamide and total body irradiation, followed by marrow rescue. The diagnosis of myelomonocytic acute leukaemia was performed 8 months later. The patient died after a transient improvement following a treatment by hydroxyurea. The roles of the primary tumour, of the chemotherapy and of the marrow transplantation in the occurrence of leukaemia are discussed.

We report the case of a 51-year-old woman presenting t(4;11) acute undifferentiated leukemia 19 months after initiation of adjuvant radio-chemotherapy for a breast cancer. Morphology of the blasts was FAB L2 and cytochemical and immunological studies were in favor of an undifferentiated leukemia. A possible relationship between t(4;11) leukemia and exposure to carcinogens is discussed.

We designed a multicenter randomized trial comparing chemotherapy with daunorubicin-Ara C (chemotherapy group) and all transretinoic acid (ATRA) combined to the same chemotherapy (ATRA group) in newly diagnosed APL patients aged 65 years or less. The major endpoint of the study was event-free survival (EFS) (“events” being defined as failure to achieve complete remission [CR], occurrence of relapse, or death in CR). Early termination of the trial was decided after the first interim analysis, as EFS was significantly higher in the ATRA group. At the time, 101 patients had been randomized (54 in the ATRA group and 47 in the chemotherapy group). In the ATRA group, 49 (91%) patients achieved CR, 5 (9%) had early death, and 0 had resistant leukemia, compared with 38 (81%), 4 (8%), and 5 (10%) patients, respectively, in the chemotherapy group. The difference in CR rate between the two groups was not significant. The duration of coagulopathy was significantly reduced in the ATRA group, compared with the chemotherapy group. In the ATRA group, six patients relapsed after 7 to 15.5 months. In the chemotherapy group, 12 patients relapsed after 1 to 16 months, and 2 died in CR. Kaplan-Meier EFS was estimated at 79% +/- 7% and 50% +/- 9% at 12 months, respectively, in the ATRA and the chemotherapy group (P = .001). Kaplan-Meier estimate of relapse was 19% +/- 8% and 40% +/- 12% at 12 months (P = .005). In conclusion, ATRA followed by chemotherapy increases EFS in newly diagnosed APL. These results strongly suggest that ATRA should be incorporated in the front line therapy of newly diagnosed APL.

From October 1987 to December 1990, 101 patients with acute myeloid leukemia (AML) were randomized to be transplanted in first complete remission (CR1). Preparative regimen including Cytoxan (120 mg/kg) with total body irradiation (CYTBI) (N = 50) or busulfan (16 mg/kg) (BUSCY) (N = 51) was followed by allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. Mean time between diagnosis and BMT was 119 days. The outcome for CYTBI at 2 years is better for probability of disease-free survival (DFS) (72% v 47%) (P less than .01), survival (75% v 51%) (P less than .02), relapse (14% v 34%) (P less than .04), and transplant mortality (8% v 27%) (P less than .06). In multivariable analysis, higher relapse and decreased survival and DFS were associated with BUSCY regimen, while chronic graft-versus-host disease also influenced independently the probability of relapse. This demonstrates the present limitation of busulfan use in this setting, possibly due to probable individual variations in biodisponibility. Furthermore, besides the anti-leukemic effect of preparative regimens, this trial points out the progress accomplished in BMT management (transplant mortality = 8% in CYTBI) over the last 20 years as well as the effectiveness of transplant in early first CR after CYTBI (DFS = 72% at 2 years).

It has been shown that all-trans retinoic acid (ATRA) at doses of 45 to 100 mg/m2/d induces complete remission (CR) of acute promyelocytic leukemia (APL) by a differentiation process. To date, ATRA dose-ranging studies have not yet been evaluated. Thus, we initiated in May 1990 a multicenter study with ATRA at a lower dose of 25 mg/m2/d until CR. Thirty patients with APL were treated with ATRA, of whom 12 were previously untreated, 14 were in first relapse, and 4 had failed after conventional first induction chemotherapy. Twenty-four of 30 achieved CR, 3 failed, and 3 died before day 30. Median time to CR was 45 days. Hyperleucocytosis (14 to 43 x 10(9) white blood cells per liter) was observed in 9 patients between days 10 and 23. Clinical complications that may have been related to the retinoic acid syndrome were observed in 8 patients, of whom 3 died. Pharmacokinetics studies were performed in 5 patients. Peak plasma concentrations and mean area under the concentration-time curve were not lower than previous levels obtained under the 45 mg/m2 dose. Overall, our study shows that there is no difference in terms of therapeutic efficacy, triggering of hyperleukocytosis, or retinoic acid syndrome and pharmacokinetic results with ATRA at 25 or 45 mg/m2/d.

Detachment of glycol methacrylate sections from glass slides is a common problem during histochemical and immunohistochemical procedures, particularly when large or hard tissue sections are stained and when using caustic solutions, alcohols, or proteases.

A 26-year-old man with hypereosinophilic syndrome who had initial neurologic, cardiac, and pulmonary dysfunction, high eosinophil count, thrombocytopenia, and bone marrow fibrosis had only a transient response to conventional treatment with corticosteroids and hydroxyurea. He therefore received human lymphocyte antigen-identical allogeneic bone marrow transplantation (BMT) after conditioning with cytoxan and fractionated total body irradiation. Hematologic recovery was prompt, with normalization of blood counts and bone marrow. The patient died less than 3 months after transplantation from diffuse cytomegalovirus infection. Potential interest of BMT in patients with resistant hypereosinophilic syndrome and features of poor prognosis is discussed.