Domenico Giordano

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.

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.

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.

Twelve Years Experience with High-Dose Therapy and Autologous Stem Cell Transplantation for High-Risk Hodgkin's Disease Patients in First Remission After MOPP/ABVD Chemotherapy

High-dose therapy followed by autografting can cure patients with aggressive Hodgkins disease (HD) refractory or with early relapse to first-line combination chemotherapy. On the other hand, the eradication of the disease is rarely achieved in heavily pretreated patients. It has been suggested that patients with HD with very high risk characteristics at diagnosis, often relapse despite appropriate therapy with 7-8 drugs combination. Thus it seems to us that such patients are potential candidates for early autografting during first remission. Twelve years ago, we initiated a pilot study to investigate whether patients with very high risk characteristics, would benefit from early autografting. The application of early autografting was compared with our historical group of patients in complete remission after receiving MOPP/ABVD, who had the same negative prognostic characteristics, refused autografting and who did not receive other treatment after achieving complete remission. Among the 22 consecutive patients entered into the pilot study and autografted, 18 are alive and 17 (77%) remain alive in unmaintained remission at a median of 86 months. One patient (4%) died of interstitial pneumonitis in the transplantation group. Only 8/24 (33%) patients, who did not receive an autograft, are currently alive and disease free at a median of 89 months. In conclusion, the early application of autografting appears to improve the outcome in patients with very high risk HD who achieved remission with MOPP/ABVD.

A to O Bone Marrow Transplantation in Severe Aplastic Anaemia: Dynamics of Blood Group Conversion and Demonstration of Early Dyserythropoiesis in the Engrafted Marrow

Summary. A to O bone marrow transplantation was performed in a 25‐year‐old male affected with severe aplastic anaemia, the donor being an HLA compatible brother. Three plasma exchanges had to be performed with an Aminco separator to remove the original and recurring anti‐A isohaemagglutinins. The dynamics of O to A blood group conversion were followed by means of differential agglutination. An early wave of marked dyserythropoiesis was observed in the engrafted marrow. Mild to moderate GvHD was treated successfully with MTX, bolus high dosage 6‐methyprednisolone and, at relapse, with intravenous ALG.

High-dose chemotherapy and non-frozen autologous bone marrow transplantation in relapsed advanced lymphomas or those resistant to conventional chemotherapy

Ten patients with advanced, diffuse Hodgkins and non‐Hodgkins lymphomas responding poorly to the most widely employed primary chemotherapy regimens were treated with a high‐dose chemotherapy (HDC) followed by rescue with non‐frozen autologous bone marrow infusion (ABMT). Complete remission (CR) was obtained in seven of ten patients (70%) and partial remission in two. Hemopoietic recovery occurred in nine cases. These preliminary results appear to indicate that HDC and non‐frozen ABMT may be successfully used in patients with resistant or relapsed lymphomas.

Philadelphia‐chromosome‐negative peripheral blood stem cells can be mobilized in the early phase of recovery after a myelosuppressive chemotherapy in Philadelphia‐chromosome‐positive acute lymphoblastic leukaemia

Ten patients in first or second relapse with Philadelphia chromosome acute lymphoblastic leukaemia, ineligible for allogeneic sibling marrow transplantation, were treated with an intensive chemotherapy regimen including idarubicin, intermediate‐dose arabinosylcytosine, etoposide and G‐CSF. Peripheral blood stem cells were collected by leukapheresis during initial early WBC recovery from chemotherapy‐Induced aplasia. In 5/10 patients all metaphases in leukapheresis products were found to be Philadelphia‐chromosome‐negative and they have been used as autotransplants after conditioning with TBI/etoposide/cyclophosphamide (or idarubicin) and G‐CSF. All five patients showed sustained engraftment and one of them is alive and well Philadelphia‐chromosome‐negative 18 months after transplant. These preliminary results suggest that it is possible to recover Philadelphia‐chromosome‐negative blood stem cells after intensive chemotherapy, even in advanced patients, and to perform autografting with these cells.

Idarubicin in combination with intermediate-dose cytarabine in the treatment of refractory or relapsed acute leukemias.

13 patients with refractory or relapsed acute lymphoblastic leukemia (ALL) and 7 patients with acute myeloid leukemia (AML) were treated with a regimen that included idarubicin 12 mg/m2 intravenously daily for 3 d plus cytarabine 2 g/m2 by infusion over 3 hours daily for 3 d. There were 10 remissions (ALL:7; AML:3) in the 15 relapsed patients and 4 (ALL:3) in the 5 patients with primary refractory disease. Severe myelosuppression was observed in all patients. Toxicity of this regimen caused nausea and vomiting, stomatitis, infections and/or liver enzymes increase. Cardiac toxicity was not observed. 2 patients died in aplasia of Gram‐negative septicemia and brain hemorrhage. In conclusion, the combination of idarubicin and intermediate‐dose cytarabine (IDARA‐C) seems to be highly effective and sufficiently well‐tolerated for the treatment of refractory and relapsed acute leukemias.

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