Raffaella Cerri

Severe Aplastic Anaemia: Correlation of in Vitro Tests with Clinical Response to Immunosuppression in 20 Patients

Summary. Colony formation in agar (CFU‐c) was studied in 20 patients with severe aplastic anaemia by three different assays: (1) cultures of light density untreated marrow cells; (2) cultures of marrow cells manipulated in order to enhance colony formation (pretreatment with antilymphocytic globulin, ALG, or 6‐methylprednisolone, 6‐MPr, T cell depletion, adherent cell (AC) depletion, depletion of both AC and T cells), and (3) co‐culture of putative suppressor T cells with autologous T‐depleted marrow cells.

Acute lymphoblastic leukaemia occurring as second malignancy : report of the GIMEMA Archive of Adult Acute Leukaemia

Between July 1992 and June 1996, 901 new cases of adult acute lymphoblastic leukaemia were recorded in the GIMEMA Archive of Adult Acute Leukaemia; 21 of them (2.3%) had a previous primary malignancy (PM). We found that secondary acute lymphoblastic leukaemia cases (sALL) presented with older age, a high incidence of pre‐pre‐B immunophenotype and a significantly higher prevalence of cancer among relatives compared to de novo ALL.

Massive chemotherapy with non-frozen autologous bone marrow transplantation in 13 cases of refractory Hodgkin's disease

A group of 13 patients with advanced, diffuse Hodgkins disease, poorly responding to the most widely employed primary chemotherapy regimens, were treated with massive chemotherapy (MCH) followed by rescue with non-frozen autologous bone marrow infusion (ABMT). Complete remission (CR) was obtained in 8/13 patients (61.5%) and partial remission in two. Hematopoietic recovery occurred in 12 cases. These preliminary results would seem to indicate that MCH with non-frozen ABMT may be successfully used in patients with resistant or relapsed Hodgkins disease.

Alpha-interferon as induction and maintenance therapy in hairy cell leukemia:a long-term follow-up analysis

Abstract: Although in recent years the use of purine analogues has increased the percentage of long‐term complete response the effect on overall survival of HCL patients is not yet clear. This study aimed to evaluate the long‐term outcome (mean follow up of 92 months) of sixty‐four patients receiving IFN as first‐line therapy. IFN was well tolerated and effective. The overall response rate was 91% (PR 65%, CR 13%, GPR 13%). Forty‐one patients (63%) received IFN 3 MU/wk as maintenance therapy. The 10‐yr projected survival rate of responding patients (CR and GPR 100%; PR 95%) and non responders (SD, PD 80%) clearly shows that type of response does not affect survival. Patients receiving IFN maintenance had a statistically higher PFS than those who did not (p<0.01). This study shows that IFN is still one of the standard therapies for this disease, that achieving CR has no primary relevance for the control of the disease, and that good utilization of therapeutic resources may assure HCL patients a survival rate comparable to that of a normal, healthy population.

First Line Therapy with Fludarabine Combinations in 42 Patients with Either Post Myelodysplastic Syndrome or Therapy Related Acute Myeloid Leukaemia

Acute myeloid leukaemias (AML) evolving from a myelodysplastic syndrome (MDS) or secondary to chemoradiotherapy frequently display unfavorable biologic characteristics. This may explain the lower remission rate obtained with conventional chemotherapy. Recently, the association of Fludarabine with intermediate dose Ara-C has produced interesting results particularly in high risk AML patients. Here, we report on 42 secondary AML patients treated with a combination of Fludarabine, intermediate dose Ara-C, G-CSF with or without an antracycline (FLANG, FLAG-IDA or FLAG). Overall, complete remissions (CR) were documented in 14 patients (33%) and partial responses (PR) in 12 (29%), while 10 patients proved resistant (24%). Six patients (14%) died early. The presence of a prognostically unfavorable karyotype had a negative impact on the CR rate (20% compared to 50% for patients with an intermediate prognosis karyotype, p 0.05). Patients treated with FLAG, FLANG and FLAG-IDA had similar CR rates. At the time of this analysis, after a mean follow-up of 12 months, the mean duration of CR is 16 months (range 3–66) and the mean survival is 11 months (range 1–67). The median time to granulocyte recovery (neutrophils > 0.5 × 109/1) was 20 days (range 12–39) and 50 × 109/1 platelets were reached at a median of 26 days (range 9–56). Taken together, these Fludarabine containing regimens proved to be an effective and tolerable treatment for patients with secondary AML. Patients above 70 years of age may also benefit from this therapy, however the problem of treating patients with adverse chromosomal abnormalities still remains unresolved.

Acute myeloid leukemia in patients previously diagnosed with breast cancer: Experience of the GIMEMA group

OBJECTIVE To evaluate in a multicenter retrospective study, the clinical and laboratory characteristics and the outcome of patients with acute myeloid leukemia (sAML) previously diagnosed with breast cancer (BC) among an adult acute leukemia population. PATIENTS AND METHODS Between June 1992 and July 1996, 3934 new cases of adults with acute leukemia were recorded in GIMEMA Archive of Adult Acute Leukemia (2964 AML, 901 ALL, 69 acute leukemia expressing both myeloid and lymphoid surface markers). RESULTS Two hundred patients (5.1%) presented with a history of previous malignancy (21 of them were affected by ALL and 179 by AML). Among sAML, 37 patients (29%) had a previous breast cancer. They consisted of 36 females and 1 male, median age 56 years, range 34-87. The median latency between the 2 malignancies was 54 months (range 5-379). Twenty-seven patients received chemo- and/or radiotherapy for breast cancer (7 only chemotherapy, 6 only radiotherapy, and 14 combined treatment). All patients were surgically treated but in 10 patients surgical debridement was the sole therapy for breast cancer. The drugs most frequently employed were alkylating agents (18 patients), topoisomerase II inhibitors (9 patients), antimetabolites (20 patients) (CMF, CEF and MMM combinations). At onset of sAML the median WBC count was 7.7 x 10(9)/l (0.8-153) and the median platelet count was 33.5 x 10(9)/l (3-305). Considering morphological features, FAB subtypes were 4 M0, 5 M1, 11 M2, 5 M3, 8 M4, 3 M5, and 1 M6. Cytogenetic study was performed on 28 patients and 12 of them presented abnormalities. It is noteworthy that chromosome 5 or 7 abnormalities (typically observed in those patients treated with alkylating agents) were present only in three cases. Thirty-four patients received chemotherapy for sAML, and twenty-five of them achieved a CR (74%), with a median duration of twenty-eight weeks (5-280+). The overall survival was 8 months (1-80+). DISCUSSION The high number of sAML we observed in patients with a previous breast cancer, may be due to the fact that this malignancy is the most frequent neoplasm in women and by the high probability of cure with a consequent long disease-free survival. Our results suggest that the risk of sAML after recovery from breast cancer is increasing due to the rise in the number of patients cured from breast cancer, and in the future could be a relevant problem for haematologists.

Acute promyelocytic leukaemia: epidemiology and risk factors. A report of the GIMEMA Italian archive of adult acute leukaemia

Abstract: Acute promyelocytic leukaemia (APL) exhibits peculiar epidemiological, clinical, cytogenetic and molecular features, compared to the other acute myeloid leukaemias (AML). Data on epidemiology and occupational risk factors for APL desumed from the GIMEMA archive are reported and compared with those of the other AML. An exploratory case‐case study was designed on AML patients from 56 haematology centres in Italy. Overall, 4296 patients older than 15 yr with a new diagnosis of acute leukaemia were recorded between July 1992 and July 1997. Of these, 335 were classified as APL, and 2894 as other AML. The median age of APL patients was 43 compared to 59 yr for the other AML (p< 0.00001). In order to identify peculiar risk factors for APL development, different parameters were compared in the 2 groups. After adjusting by age no significant differences were observed with regard to education, lifetime prevalence of cancer among siblings and previous diseases in the patients history. Occupational exposure as a possible risk factor for APL showed no increased risk compared to other AML among farmers, builders and leather workers. A significant association was found in electricians (OR = 4.4, 95% CI = 2.0–9.7) and a weak association was found in wood workers (OR = 3.2, 95% CI = 0.8–10.8). The proportion of APL with respect to other AML was significantly higher in the north east of Italy compared to the rest of the country (OR = 1.7, 95% CI = 1.3–2.2). These data confirm the younger age of APL patients compared to the other AML. A possible role of electromagnetic fields is suggested by the higher risk of APL in electrical workers and in the more industrialized areas of the country.

Idarubicin in Combination with Etoposide and Cytarabine in Adult Untreated Acute Non Lymphoblastic Leukemia

Thirty-one unselected patients with untreated acute non lymphoblastic leukemia (ANLL) ranging in age from 15 to 76 years received two courses of a new high-dose induction regimen consisting of idarubicin, etoposide and cytarabine. Patients who entered complete remission (CR) were then allocated to post-remission intensification (PRI). Patients under 40 years of age with a HLA-compatible donor were given bone marrow transplantation (BMT); those without an HLA identical donor received either autologous BMT (ABMT) or no subsequent therapy. Twenty-five out of 31 patients (80.6%) achieved CR (93.3% in young and 68.7% in old patients) and 14 (56%) after the first cycle. Six patients (five out six greater than 40 years) died of cerebral hemorrhage and/or infection during the induction phase and four additional patients (three elderly) died on the PRI for the same cause without recurrent disease. Eleven out 25 patients are disease-free survivors 2-34 months (median 10 months) after achievement of CR. In conclusion, this intensive chemotherapy regimen is effective both in young and older patients but the post-remission intensification is too aggressive in elderly patients.

A New Combination of Idarubicin, Etoposide and Cytarabine in Untreated Acute Non-Lymphoblastic Leukemia

Sixty-seven unselected adult patients with untreated acute non lymphotblastic leukemia (ANLL) ranging in age from 15 to 80 years received a new induction regimen consisting of Idarubicin, Etoposide and Cytarabine. Patients who entered complete remission (CR) were then allocated to 4 courses of post remission intensification. After this, patients under 50 years of age with a compatible donor were given allogeneic bone marrow transplantation (BMT) or autologous BMT (ABMT) in those without an HLA-compatible donor; the remainder, older than 50, did not receive further therapy. Fifty-six of 67 patients (83.5%) achieved CR (02.5% in young and 70.3% in old patients) and 40 (71 %) after the first course. Seven patients (of whom, 6 were > 50 years) died in aplasia during the induction phase and four additional patients (all elderly) died during post-remission intensification without recurrent disease. Subsequently, the younger patients received transplants (BMT: 4 pts; ABMT: 10 pts). Twelve: of the 52 (23%) who survived post remission intensification (BMT: 1; ABMT: 4; others: 7) are disease free survivors 9-67 months (median, 32 months) after achieving CR. In conclusion, this intensive chemotherapy regimen is highly effective both in young and odder patients but the post-remission intensification may be too aggressive for elderly patients.