Thirty-two patients with refractory acute myeloid leukemia (AML) received salvage therapy with a single course of mitoxantrone 6 mg/m2 intravenous (IV) bolus, etoposide 80 mg/m2 IV for a period of 1 hour, and cytarabine (Ara-C) 1 g/m2 IV for a period of 6 hours daily for 6 days (MEC). Eighteen patients were primarily resistant to conventional daunorubicin and Ara-C induction treatment; eight patients had relapsed within 6 months from initial remission; six patients had relapsed after a bone marrow transplantation (BMT) procedure. Overall, 21 patients (66%) achieved a complete remission (CR), two (6%) died of infection during induction, and nine (28%) had resistant disease. Age greater than 50 years was the only factor predictive for a significantly lower response rate (P = .03). The median remission duration was 16 weeks; the overall median survival was 36 weeks. Severe myelosuppression was observed in all patients resulting in fever or documented infections in 91% of patients. Nonhematologic toxicity was minimal. We conclude that the MEC regimen has significant antileukemic activity and acceptable toxicity in salvage AML. Its benefit in front-line AML therapy is being investigated.

Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3 þ 7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (Po0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P ¼ 0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

The proportion of ciprofloxacin-resistant Gram-negative bacteria isolated from the blood of children with cancer (not receiving prophylaxis) was 10% in a paediatric hospital (Genoa) where the use of quinolones was highly restricted, compared with 41% in a department of haematology (Rome) where leukaemic adults, who received fluoroquinolone prophylaxis, were also treated (p < 0.0001). Moreover, simultaneous resistance to ciprofloxacin and ceftazidime, amikacin or imipenem-cilastatin was 11% in Genoa compared with 37% in Rome (p < 0.001). Ciprofloxacin resistance was more frequent in children who shared an environment with adults who were receiving ciprofloxacin prophylaxis.

The immunologic features of leukemic cells at the time of 1stondary acute myeloid leukemias (AML) has been described in hematologic relapse were compared to those obtained at initial children previously treated for ALL with regimens containing diagnosis in 128 patients (69 children and 59 adults) with acute teniposide on a twice weekly schedule. 8,9 It is, therefore, use- med in all children and adults with ALL in 1st relapse at ourIn 21 cases, the immunophenotype at relapse was more undifferentiated than at diagnosis, while it was more differentiated Institution and compared to the phenotype observed at diag- from 0.1 to 85 years. The diagnosis of ALL was based on FAB Keywords: immunophenotype; lymphoblastic; leukemia; relapse criteria 10 and immunophenotype. [11][12][13] Response to treatment was evaluable in 482 patients. The 32 unevaluable cases included 18 referred only for diagnosis and 14 that were Introduction treated only with palliative therapy. 443 patients achieved a complete remission (CR) (92%) and 209 of these subsequently Relapses of acute lymphoblastic leukemia (ALL) occur with relapsed. A comparison between the immunophenotypic prodifferent frequencies according to patients' age, being higher files at relapse and at diagnosis was not carried out in 14 in infants and adults compared to children. Several studies patients who presented at relapse with Ͻ30% blasts in the have focused on the immunophenotype of the leukemic popubone marrow aspirate and in 67 patients because of an incomlation at the time of relapse compared to that observed at diagplete immunophenotype performed at the time of presentation nosis. [1][2][3][4][5][6][7] Although in the majority of cases a modification in and/or at 1st relapse. A total of 128 patients were evaluable, the phenotypic profile of the neoplastic clone does not occur, including 69 children (median age 7 years, 0.2-14.8) and 59 in a notable number of B and T lineage ALL immunophenoadults (median age 30.8 years, 15-67). Median duration of 1st typic changes have been recorded. In most cases, these are CR was 16 months (range 2-80), shorter than 1 year in 51 represented by a loss of differentiation antigens, suggesting patients and longer in 77. All patients were treated at diagthat relapses may originate from a more undifferentiated subnosis and at relapse with anti-ALL chemotherapy regimens in clone of leukemic blasts. In childhood ALL, an overall change order to achieve CR and long-term event-free survival (EFS). in the immunophenotype at relapse does not seem to influSince over the years different treatment protocols were ence the response to salvage therapy, but relapses of T lineage employed these have been grouped under two major categor-ALL have been associated with a worse outcome compared ies: standard and intensive. Standard treatment schemes to B lineage ALL. 5 included a four drug induction (anthracycline, vincristine, L-A phenotypic change at relapse does not necessarily imply asparaginase, prednisone), followed by consolidation, reinthat a new l...

Summary:The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9) ) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P Ͻ 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse. Keywords: childhood lymphoblastic leukemia; meningeal relapse; autologous marrow transplantation Isolated CNS relapse occurs in 5-10% of children with ALL treated with risk-directed therapy.1,2 In most experiences, patients who despite an adequate front-line CNS prophylaxis experience a meningeal relapse have a poor 3 Retreatment induces a second CR but due to further relapses the event-free-survival (EFS) is in the 20-30% range, with few exceptions.2-8 Successful treatment of CNS relapse must include CNS-directed and intensive systemic therapy. Major CNS problems have been described in long-term survivors after conventional retreatment. 9 The role of BMT in the therapeutic strategy of isolated CNS relapse has only recently been explored, with controversial results.7,10-12 Our study investigates the role of ABMT in a relatively large series of 60 children with ALL, who developed a first isolated CNS relapse early, ie within 3 years of diagnosis. Of these, 19 underwent ABMT, while 41 had chemotherapy only; we also include our limited experience on nine patients who had ALLO-BMT. This retrospective study has been based on the experience of all the AIEOP centers that considered ABMT as a therapeutic option for ALL children after an isolated CNS relapse from 1986 to 1992. The analytical method adopted here aimed to exclude any biases related to the retrospective nature of the study and the waiting time before transplantation. Patients and methods PatientsCNS relapse was defined as the presence in the cerebrospinal fluid of Ͼ5 mononuclear cells per microliter, morphologically identified as lymphoblasts on cytospinning. ABMT and, to a lesser degree, also ALLO-BMT, have been considered as a therapeutic option after an isolated CNS relapse at 10 AIEOP transplantation centers since 1986. From 1986 to 1993, 20 consecutive childre...