Partial deletions of long arm of chromosome 6: biologic and clinical implications in adult acute lymphoblastic leukemia.

Within 285 adult acute lymphoblastic leukemias (ALL) included in the multicenter GIMEMA 0496 trial and prospectively studied by conventional cytogenetics, 18 cases (6%) with long arm deletion of chromosome 6 (6q) were identified. These cases were divided into: (i) del(6q) only (n = 6); (ii) del(6q) plus other numerical and/or structural abnormalities (n = 8); (iii) del(6q) and other 'specific' translocations (n = 4). The biologic and clinical features of the patients carrying this anomaly, as well as their outcome, were compared with those of 267 patients without del(6q). A T cell phenotype was more frequently associated with del(6q) cases in general (P = 0.001) and particularly with cases presenting del(6q) as the isolated abnormality (P = 0.0027). No significant difference with respect to multidrug resistance (MDR)/P glycoprotein expression was observed between the two groups of patients (21% vs 28% of MDR-positive cases, respectively). A BCR-ABL fusion transcript was less frequently detected in cases with del(6q) (11%) compared with those without the anomaly (29%). p15 and p16 deletions were identified by Southern blot analysis in 21% of cases with del(6q) and in 26% of cases without del(6q). In this latter group, a T cell phenotype was less frequently associated with p15 and/or p16 deletion than in the group carrying del(6q) (36% vs 100% of cases, P = 0.011). Overall, patients with ALL and del(6q) had a high complete remission (CR) rate (83%); however, they had a lower 18 month event-free survival (31% vs 41%) and a higher relapse rate (70% vs 37%, P = 0.02) compared with patients without del(6q). To date, this is the largest series of adult ALL cases reported with del(6q) homogeneously treated, which have also been prospectively studied for MDR expression and for the detection of known fusion genes. This anomaly, as an isolated change, identifies a subset of cases with hyperleukocytosis (median WBC count 52 x 10(9)/l) and a strict correlation with a T cell phenotype. Overall, del(6q) seems to be associated with an unfavorable clinical outcome, although this finding will need to be confirmed by extended FISH analysis.

Autologous transplantation in multiple myeloma: a GITMO retrospective analysis on 290 patients. Gruppo Italiano Trapianti di Midollo Osseo.

BACKGROUND AND OBJECTIVE: Autologous transplantation is a better treatment for multiple myeloma (MM) than chemotherapy, but uncertainty remains about patient selection, optimal timing of autograft, conditioning regimen, need for a second autograft, and role of maintenance. To provide partial answers to these questions we assessed the results of autologous transplantation in a large cohort of patients whose data were reported to the GITMO registry. DESIGN AND METHODS: We retrospectively analyzed data from 290 patients with MM (M = 150; F = 140; median age 52 years, range 19-70; stage I = 34, stage II = 75, stage III = 167) reported to the GITMO. At the time of autograft, 20% were in CR, 66% in PR, while the remaining had non-responsive or progressive disease. Median time between diagnosis and transplant was 16 months (1-90). Seventy-two patients (26%) had been planned to receive a double autograft, but this was actually done in only 35 (12%). The conditioning was chemotherapy in 90%. Peripheral blood was the only source of stem cells in 94%, and purging was applied in 10% of cases. For statistical analysis of data, differences between patient subsets were analyzed using the chi-square test, while the Kaplan-Meier method was used to estimate event-free survival (EFS) and survival (OS) probabilities. The Cox model was used for multivariate analysis. RESULTS: Following the autograft, 116 patients (40%) were in CR, 144 (50%) in PR, 24 (8%) did not respond or progressed and 6 (2%) died before response evaluation. Transplant-related mortality occurred in 3%. At a median follow-up of 23 months, 223 (77%) patients are alive, 71 (24%) of them in CR, and 67 (23%) patients have died at a median time of 20 months (0-70). OS and EFS at 6 years are 47% and 28%, respectively, but the EFS curve shows no plateau. In multivariate analysis, age, beta2-microglobulin level and status at transplant emerged as significant prognostic factors for both OS and EFS, while time from diagnosis to transplant showed borderline significance. INTERPRETATION AND CONCLUSIONS: Based on the prognostic factors identified in multivariate analysis, we were able to assess the weight of a single prognostic factor or their combinations on transplant outcome. We also calculated the probability of OS and EFS by the number of factors at the time of autograft. Autologous transplantation is a safe and effective procedure, not only in sensitive patients, but also in resistant cases, provided they are <55 years of age and have low beta2-microglobulin. It should be applied early after the diagnosis of multiple myeloma, following the delivery of brief primary chemotherapy.

Centre effect on treatment outcome for patients with untreated acute myelogenous leukaemia? An analysis of the AML 8A Study of the Leukemia Cooperative Group of the EORTC and GIMEMA. European Organization for Research and Treatment of Cancer (EORTC) Leukemia Cooperative Group and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA).

In the AML 8A study patients were treated with remission-induction therapy followed by one consolidation course. Patients in complete remission (CR) were randomised between autologous bone marrow transplantation (ABMT) and a second intensive consolidation course, except for those with a histocompatible sibling donor, who received allogeneic bone marrow transplantation (alloBMT). This analysis was performed to determine whether centres which only performed induction and consolidation therapy, achieved similar results as centres who also performed transplantation. 542/676 (80%) from transplantation centres and 150/194 (77%) from referring centres achieved CR, with an early death rate of 5% and 11%, respectively (P = 0.01). 66% of patients with a donor from transplantation centres received alloBMT in first CR compared with 57% from referring centres (P = 0.2). Transplantation centres randomised 64% of patients without a donor, referring centres 47% (P = 0.04). The full protocol treatment was completed by 275/542 (51%) and 61/150 (41%) patients, respectively (P = 0.04). The overall survival rate at 6 years from diagnosis was 34% and 36%, respectively (P = 0.9). In conclusion, the type of centre did not appear to have an influence on overall survival. The feasibility of the study was acceptable for both types of centres. The referring centres applied more selection for transplantation. Despite a more intensive second-line treatment at transplantation centres, the overall outcome remained similar to that of referring centres.

The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA. European Organization for Research and Treatment of Cancer. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P=0.01, RR 0.78, 95% confidence interval 0.63-0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P=0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.

Immunophenotype of adult and childhood acute promyelocytic leukaemia: correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases.

Acute promyelocytic leukaemia (APL), characterized by a specific PML-RARalpha fusion gene resulting from translocation t(15;17) and by a high response rate to differentiation therapy with all-trans retinoic acid, presents clinical (varying WBC counts, age and treatment outcome), morphological (hypergranular M3 and hypogranular M3V) and molecular (three isoforms of PML breakpoint) heterogeneity. We correlated leukaemic immunophenotype with these aspects in 196 molecularly confirmed APLs (63 children and 133 adults) in Italy. The bcr3 isoform (P = 0.05) and FAB M3V (P = 0.05) were more frequent in children. We confirmed in APL an immunophenotype characterized by frequent expression of CD13, CD33 and CD9 and rare expression of HLA-DR, CD10, CD7 and CD11b. However, we recognized CD2 in 28%, CD34 in 23% and CD19 in 11% of cases and demonstrated by double labelling that CD34 and CD2 may be co-expressed. CD2, CD34 and CD19 were significantly intercorrelated, and variably associated to other features: CD2 and CD34 with PML bcr3 (P < 0.001 and P < 0.001, respectively) and with M3V (P < 0.001 and P = 0.002), whereas only CD19 was directly correlated with WBC counts and only CD2 positively influenced CR rate (logistic model) and event-free survival (Cox model). We conclude that immunophenotype plays a role in the determination of the biological and clinical heterogeneity of childhood and adult APL.

p53 expression in B-cell chronic lymphocytic leukemia: a marker of disease progression and poor prognosis.

We have analyzed by immunocytochemistry (ICC) the frequency of p53 protein expression in 181 cases of B-cell chronic lymphocytic leukemia (CLL) followed at a single institution to assess the relationship between p53 and the clinical and morphological features of the disease, as well as the possible involvement of this protein in the pathogenesis of the more aggressive forms of CLL. The overall frequency of p53 protein positivity in CLL was 15% (27 of 181 cases). There were no significant differences in age, sex, absolute lymphocyte count, or lymphocyte doubling time between p53-positive and -negative patients. By contrast, p53-positive patients had a significantly higher percentage of prolymphocytes (P = .002) and a significantly lower percentage of residual CD3-positive T lymphocytes (P = .0001). No correlation was found between the percentage of p53-positive cells and the percentage of cells in cycle assessed by the monoclonal antibody Ki-67. When the percentage of p53 positivity was correlated with the clinical stage of the disease, the proportion of p53-positive cases increased significantly from Binet's stage A (8 of 108; 7.4%), to stage B (12 of 49; 24.4%) and C (7 of 24; 29.2%) (P = .002). p53 positivity correlated also with the phase of the disease, showing a low expression at diagnosis (8 of 112; 7.1%) and a significantly higher expression in patients studied during the course of the disease (7 of 35; 20%) and, to a further extent, with disease progression (12 of 34; 35.3%) (P = .0001). The association of p53 protein expression with mutations in the gene was confirmed by direct sequence of the entire cDNA in 15 of the 17 ICC positive cases tested (88%). A significantly shorter treatment-free interval from diagnosis (P = .003) and a poorer response to therapy (P = .007) was observed in p53-positive compared with p53-negative patients. Overall survival from the time of diagnosis, as well as from the time of p53 protein analysis, was significantly shorter in patients with p53 protein expression (P = .03 and .0001, respectively). Moreover, in multivariate analysis, p53 expression and stage C were independently associated with a short survival. The results of this study indicate that in CLL the expression of the p53 protein, analyzed by a simple and reliable immunocytochemical method, is strongly associated with p53 gene mutations, a morphological variant (CLL with >10% prolymphocytes), advanced clinical stage, progressive disease, poor response to therapy, and short survival.

Secondary haematological neoplasm after treatment of adult acute lymphoblastic leukemia: analysis of 1170 adult ALL patients enrolled in the GIMEMA trials. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.

Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM) was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942 patients who achieved complete remission (CR); seven developed a SHM: four AMLs and three NHLs. The median latency from onset of ALL and of secondary haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of four patients with secondary AML were unresponsive to the new chemotherapy and died, whereas the fourth patient achieved a new CR. Among the three NHL cases, two patients are presently alive in CR, whereas the third patient was refractory to chemotherapy and died. The relative risk of haematological malignancy among the GIMEMA trials population, as compared to that of the Italian Cancer Registries, was 15.25-fold higher, and the actuarial estimated cumulative proportion of ALL patients with a secondary haematological neoplasm at 5 and 10 years were 0.59% and 3.63% respectively. The incidence of adult ALL who developed a SHM, although apparently lower than in the paediatric ALL series, was higher when compared to the normal population. The difference between paediatric and adult ALL is probably due to the lack of craniospinal radiotherapy and to the lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage of childhood ALL with a prolonged event-free survival could result in an increase of secondary neoplasms in these cases, which suggests that secondary haematological neoplasms in adult ALL patients are real, although rare, events.

Immunophenotype of adult and childhood acute lymphoblastic leukemia: changes at first relapse and clinico-prognostic implications.

The immunologic features of leukemic cells at the time of 1st hematologic relapse were compared to those obtained at initial diagnosis in 128 patients (69 children and 59 adults) with acute lymphoblastic leukemia (ALL) treated at a single institution. An immunophenotypic change was observed in 59 cases (46%), more frequently in T (20/25) than in B (39/103) lineage ALL (80 vs 38%, P=0.0008), but with a similar incidence in adults and children. Of these cases, 34 (24 B- and 10 T-ALL) changed at relapse their intralineage subgroup affiliation, although no complete shift from B to T lineage ALL, or vice versa, was observed. The myeloid antigens CD13 and/or CD33 were frequently lost (2/5 cases) or acquired (12/123 cases) at relapse. In 21 cases, the immunophenotype at relapse was more undifferentiated than at diagnosis, while it was more differentiated in 13 cases. Initial treatment intensity or preceding treatment with teniposide did not affect the phenotypic profile at relapse. Complete response (CR) rate to salvage therapy and event-free survival were not influenced by the immunophenotypic shifts, nor by the presence, at relapse, of leukemic cells expressing the myeloid antigens CD13 and/or CD33. Univariate analysis suggested that prognosis after relapse was dependent on the duration of 1st CR, patients' age and immunophenotype at the time of diagnosis, with a worse outcome for patients with T lineage ALL and for patients with the less differentiated subgroup of B lineage ALL (CD19+ and CD10-). Multivariate analysis showed that only two factors, duration of 1st CR and grade of immunologic differentiation at diagnosis, have independent prognostic value in relapsed ALL.

Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups.

Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.

Multimodality treatment of thymoma: a prospective study.

BACKGROUND: Thymomas are a heterogeneous group of tumors. Treatment of invasive lesions is not well standardized. The aim of this study is to propose a clinicopathologically based protocol for multimodality therapy. METHODS: Between 1965 and 1988, we operated on 83 patients with thymoma who did not receive standardized adjuvant therapy. In 1989, on the basis of the retrospective analysis of the data, we started a multimodality therapy protocol and used it for 65 patients. Twelve patients had medullary thymoma (11 stage I and 1 stage II), 13 had mixed type (6 stage I and 7 stage II), and 40 had cortical thymoma (4 stage I, 11 stage II, 12 stage III, and 13 stage IV). We considered three groups. Group I (n = 18 patients), benign thymoma, included stage I and II medullary and stage I mixed thymomas; radical resection with no adjuvant therapy was performed. Group II (n = 22), invasive thymoma, included stage I and II cortical and stage II mixed thymomas; postoperative chemotherapy plus radiotherapy was always administered. Group III (n = 25), malignant thymoma, comprised stage III and IV cortical thymomas and stage III mixed thymomas; resectable stage III lesions were removed, and highly invasive stage III and stage IV lesions underwent biopsy, neoadjuvant chemotherapy, and surgical resection; postoperative chemotherapy and radiotherapy was administered to all patients. RESULTS: The 8-year survival rate for patients in stages I, II, III, and IV was 95%, 100%, 92%, and 68%, respectively. Patients with medullary thymoma had a 92% 8-year survival rate; those with mixed type, 100%; and those with cortical thymoma, 85%. Group I had an 8-year survival rate of 94%; group II, 100%; and group III, 76%. Survival was compared with that of patients operated on before 1989: differences were not significant for group I; survival improved in group II (100% versus 81%; p = not significant); and group III showed significant improvement (76% versus 43%; p < 0.049). CONCLUSIONS: Multimodality treatment with neoadjuvant chemotherapy and adjuvant chemotherapy plus radiotherapy may improve the results of radical resection and the survival of patients with invasive and malignant thymoma.

Prognostic factors of patients with acute myeloid leukemia (AML) allografted in first complete remission: an analysis of the EORTC-GIMEMA AML 8A trial. The European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) Leukemia Cooperative Groups.

The Leukemia Cooperative Groups of the EORTC and the GIMEMA conducted a prospective randomized phase III trial, in order to assess the value of autologous BMT (ABMT) vs a second intensive consolidation course (IC2), following a common intensive consolidation course (IC1) for patients with AML. Patients with an HLA-identical sibling donor were not randomized, but were included in an allogeneic BMT (alloBMT) program. This is an analysis of prognostic factors which influence the outcome of treatment after alloBMT in first complete remission (CR). The study included 730 patients < 46 years of age in CR, 270 having a histocompatible sibling donor. In 169 of these patients alloBMT was performed in first CR. Early remitters (122 patients achieving CR with one course of treatment) had a DFS at 3 years of 67%, significantly longer than that of 44% for late remitters (47 patients achieving CR after more than one course of treatment) (P = 0.006). The relapse risk for early vs late remitters was 16 and 40% at 3 years (P = 0.001) and the treatment-related mortality (TRM) at 2 years was 21 vs 27%. Age appeared to be a prognostic factor for TRM, WBC for DFS, whereas the FAB classification was not of prognostic importance. Patients with poor risk cytogenetic abnormalities showed a trend towards a higher relapse risk. Patients transplanted shortly after achieving CR appeared to have a worse prognosis than those transplanted further into remission. Overall, the number of courses of induction therapy needed to achieve CR was the most important prognostic factor for outcome after allogeneic BMT.

Reproducibility of the morphological diagnostic criteria for acute myeloid leukemia: the GIMEMA group experience.

Diagnostic reproducibility of the FAB morphological subtypes of acute leukemia is a basic step in the assessment of the clinical outcome in multicenter trials. Unusual cytologic variables and slightly different interpretations of the FAB morphological criteria have been the most significant factors affecting the overall diagnostic concordance rate among the various centers. An evaluation of the diagnostic concurrence between 35 institutions of the Italian Cooperative Study Group GIMEMA and two reviewers of the ad hoc morphological committee has been performed on 377 patients entering the AML 8A and AML 8B GIMEMA protocols. Overall concordance rate was 62.6%. The most significant differences were observed for M2 vs M4, M4 vs M5, M1 vs M2, and M2 vs M5 subtypes. In order to minimize the impact of some diagnostic deviations on the mean cytologic concordance rate, a distinction between "major" and "minor" discrepancies in the diagnostic procedures has been proposed. When the results of the single institutions were corrected by considering the "major" discrepancies only, a mean diagnostic agreement of 78.1% was reached.

Mitoxantrone, etoposide and intermediate-dose Ara-C (MEC): an effective regimen for poor risk acute myeloid leukemia.

A total of 74 patients with poor risk AML (median age 36.7 years, range 4.5-60.6) received a single course of a regimen including mitoxantrone (6 mg/m2 intravenous bolus daily, days 1 to 6), etoposide (80 mg/m2 intravenous over 1 h, daily, days 1 to 6) and intermediate-dose Ara-C (1 g/m2 over 6 h, daily days 1 to 6). 28 patients had failed initial remission induction with daunorubicin and conventional doses of Ara-C, 16 patients had secondary AML and 30 patients had relapsed from initial remission (five within six months, 15 over six months and ten after autologous or allogeneic bone marrow transplantation). Overall 41/74 patients (55%) achieved complete remission, 26 (35%) had resistant disease and seven (10%) died of infection during marrow hypoplasia. A 4-day course of the same regimen was given as consolidation to patients in complete remission. Subsequent antileukemic therapy was individualized. Profound myelosuppression and pancytopenia were universal resulting in fever or documented infections in almost 100% of patient; major hemorrhagic complications occurred in 39% of patients. Extrahematologic toxicity was mild to moderate consisting mostly of nausea and vomiting, oral mucositis and transient liver and cardiac dysfunction. We conclude that the MEC combination chemotherapy program seems to be an effective antileukemic regimen for secondary and advanced AML, with acceptable toxicity.

A randomized study of the efficacy of postconsolidation therapy in adult acute nonlymphocytic leukemia: a report of the Italian Cooperative Group GIMEMA.

The Italian Co-operative Group GIMEMA conducted a randomized trial in adult acute nonlymphocytic leukemia (ANLL) to assess the role of postconsolidation treatment. Of 448 evaluable patients entered into the study, 305 (68%) achieved a complete remission after a standard induction with daunorubicin and cytosine arabinoside (3 + 7; 2 + 5). Those in remission after a consolidation therapy including 4 courses of daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT) were allocated to one of three arms: no treatment, conventional maintenance, or intensive postconsolidation therapy. The median disease-free survival (DFS) was 13 months, and the median survival was 14 months, with 26% surviving at 6.5 years. There was no difference in survival and in disease-free survival among the three postconsolidation arms. In conclusion our study, as others, suggests that the critical period of ANLL treatment is within the first 5-6 months.

Is interferon alpha in cutaneous T-cell lymphoma a treatment of choice?

This study was designed to evaluate the therapeutic efficacy and toxicity of recombinant interferon alpha-2a (rIFN alfa-2a) given as initial systemic therapy in untreated mycosis fungoides and/or Sezary's syndrome patients, at a slowly escalating schedule up to the maximal tolerated dose. At the same time this schedule was administered in patients who had relapsed or were refractory to previous treatment; 28 newly diagnosed and 15 previously treated patients entered the study. IFN was given daily with dose escalation from 3 to 18 MU. The last follow-up in June 1990 indicates that 90% of previously untreated patients who obtained a complete remission remain in continuous complete remission after 18 to 40 months and that 75% of previously untreated patients who obtained partial remission remain in partial remission after 20-44 months. The event-free survival projected, calculated using the Kaplan and Meier product limit technique, was 21% of all patients at 54.7 months (40% in the previously untreated groups and 14% in the previously treated group: P = 0.12). In conclusion, interferon is very effective as a single agent in cutaneous T-cell lymphomas.

Epidemiology of acute promyelocytic leukemia in Italy. APL Collaborating Group.

This retrospective epidemiologic study on 256 cases of Acute Promyelocytic Leukemia (APL) observed in 20 Italian hematology centers between 1980 and 1988 demonstrated that APL is different from the other acute non-lymphocytic leukemias (ANLL). The male/female ratio was 0.9; median age at diagnosis was 40 years (with 80% of patients between 15 and 54 years of age). The minimal annual incidence of APL in Italy per 1,000,000 inhabitants was estimated to be 0.6; an increased incidence was observed in spring and in autumn. The overall median survival duration of APL patients was 12.6 months. From an epidemiological point of view APL is a distinctive subtype of ANLL.