Marco Risso

4-Demethoxydaunorubicin (Idarubicin) in refractory or relapsed acute leukemias. A pilot study

Twenty‐five adults with previously treated acute leukemia were treated with 4‐demethoxydaunorubicin (Idarubicin) with a daily dose of 8 mg/m2 for 3 days intravenously. Complete remission was achieved in 3 of 18 patients with acute nonlymphoblastic leukemia (ANLL) and 2 of 6 with lymphoblastic leukemia. Complete remissions were observed in two of eight ANLL patients refractory to cytarabine, anthracycline, and m‐Amsa (amsacrine), indicating a lack of cross‐resistance between these drugs and Idarubicin. The median duration of remission was 8 weeks. The main major toxicity of Idarubicin therapy, severe myelosuppression, cannot be considered a toxic effect because it was desired in this case list. Our preliminary results indicate that Idarubicin has significant activity against refractory adult acute leukemia.

Improved outcome in young adults with de novo acute myeloid leukemia in first remission, undergoing an allogeneic bone marrow transplant

We assessed the outcome of 170 patients with AML in first complete remission, aged 1–47 years (median 29), who had undergone an allogeneic BMT before or after 1990 (n=80 and n=90, respectively); all patients were prepared with cyclophosphamide and TBI; the median follow-up for surviving patients was 13 years. The donor was an HLA-identical sibling in 164 patients. Transplant-related mortality (TRM) was 30% before and 7% after 1990 (P<0.001); relapse-related death (RRD) was 26 and 11% (P=0.002); and actuarial 10-year survival was 42 and 79% (P<0.00001). Patients transplanted after 1990 were older, had a shorter interval diagnosis-BMT, had less FAB-M3 cases, received a higher dose of TBI, a higher marrow cell dose and combined (cyclosporine+methotrexate) GVHD prophylaxis. Patients relapsing after transplant had an actuarial survival of 0 vs 31% if grafted before or after 1990 (P=0.01), and their median follow-up exceeds 10 years. In conclusion, the overall survival of first remission AML undergoing an allogeneic BMT has almost doubled in the past two decades, despite older age and fewer M3 cases. Improvement has come not only from changes in transplant procedures, but also from effective rescue of patients relapsing after transplant.

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.

Bone Marrow Transplantation for Severe Aplastic Anemia

9 patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation (BMT). 5 were conditioned with cyclophosphamide and received and HLA-identical graft (4 patients) or a mismat

Autologous Unpurged Bone Marrow Transplantation for Acute Non Lymphoblastic Leukemia in First Remission

Forty consecutive adult patients under the age of 50 with acute non-lymphoblastic leukemia (ANLL) in first complete remission, underwent autologous bone marrow transplantation (ABMT) between March 1984 and April 1990. The conditioning regimen employed included cyclophosphamide and total body irradiation, followed by the administration of unpurged ABMT. The median time from diagnosis to transplant was 7 months (3-15 months), and the median time from complete remission to ABMT was 4 months (range 3-9 months). Twenty-two (51%) patients remain in complete remission 6-81 months (median 24 months) after ABMT. The causes of death were, recurrent leukemia (11 patients), parenchymal toxicities such as acute respiratory distress syndrome and veno-occlusive disease (3 patients), hemorrhage (2 patients) and infection (2 patients). Eleven patients relapsed after 3-12 months (median 5 months). This study has produced survival data comparable to those of other institutions employing TBI for either allo or autotransplants.

NOLA1 gene mutations in acquired aplastic anemia

Telomerase complex genes mutations (DKC1, TERC, TERT, and NOP10) lead to premature telomere shortening and are responsible for different forms of dyskeratosis congenita. TERC and TERT mutations were also found in patients with aplastic anemia. The aim of this work is to analyze the possible involvement of the telomerase complex gene NOLA1, in a population of Italian AA patients.

Positive direct antiglobulin tests and heteroimmune hemolysis in patients with severe aplastic anemia and pure red cell anemia treated with antilymphocytic globulin.

Forty-six patients with severe aplastic anemia (SAA), 1 with adult pure red cell aplasia (PRCA), 1 with congenital hypoplastic anemia (Diamond-Blackfan) and 1 with severe polymyositis were treated with intravenous antilymphocyte globulins (ALG) of different sources (2 of equine and 1 of rabbit origin). In all patients, direct and indirect antiglobulin tests (DAT and IAT) were performed, and in all patients treated with one type of equine ALG, positive DATs were found in Rh0(D)-positive patients, while the serum of Rh0(D)-negative patients treated with the same ALG reacted in vitro with Rh0(D)-positive erythrocytes. The antibody was eluted and shown to be of equine origin. Two patients suffered from frank heteroimmune hemolytic anemia. Since October 1984, the ALG of this particular source has not displayed any overt anti-erythrocyte activity any more. However, all clinicians treating patients with this type of immune immunosuppression should know that ALG may retain human erythrocyte (presumably anti-LW) activity.

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.