Search

We designed a post-induction therapy including intensive sequential therapy with non-cross-resistant drugs in an effort to prolong disease-free survival (DFS) for adults with acute myelogenous leukemia. Forty-five patients entered this study and 33 of 35 patients entering complete remission received the post-induction therapy. With a median follow-up for survivors of 3.5 years from complete remission, the actuarial 5-year DFS was 46% ± 19% (95% confidence interval). The five-year DFS for patients over 45 years of age was comparable to that for patients under 45 years of age (50% ± 26% vs 47% ± 28%). Furthermore, the actuarial 5-year DFS for patients who required two courses of induction therapy was comparable to that for patients who required only one course of induction therapy (45% ± 29% vs 50% ± 25%). The toxicity of post-induction therapy was tolerable and no patients died during complete remission.

Thirty-two patients with advanced non-Hodgkin's lymphoma (NHL) with aggressive histologic findings were treated with cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide, and prednisolone (CAMBO-VIP), in which presumably non-cross-resistant myelosuppressive and nonmyelosuppressive agents were administered during alternate weeks for 12 weeks. To ensure the high-dose intensity of the protocol, dose reduction and delay in treatment were minimized. Three patients were treated inadequately. Twenty-six (89.7%) of 29 evaluable patients had a complete response, and three had a good partial response. Relapse occurred in four patients, with a median follow-up of 29 months. The actuarial overall survival and disease-free survival were estimated to be 87.6% and 75.9%, respectively. The CAMBO-VIP treatment was well tolerated; myelosuppression was severe but transient and caused no serious infections. Side effects that affected dose intensity were oral ulceration, occurring in 28 patients, and blister formation under the thickened skin of palms and/or soles, followed by desquamation (5 patients). Hepatic toxicity was generally mild to moderate; it was severe in one patient. A 12-week regimen of CAMBO-VIP was effective for advanced NHL with aggressive histologic findings.

Twenty-five pediatric patients who received bone marrow transplantation (BMT) were studied prospectively to determine the relationship between BMT and human herpesvirus-6 (HHV-6) infection by the virus isolation from peripheral blood and/or bone marrow and by determining neutralizing antibodies to HHV-6 during the 2 months following BMT. All of the 25 donors and the recipients were immune to HHV-6 at the time of BMT and the virus was not isolated from them. HHV-6 was isolated from peripheral blood and/or bone marrow mononuclear cells in ten (40%) of the 25 recipients between day 14 and day 22 of BMT, but not from any other day. Two additional recipients showed a significant increase in the antibody titer. Thus, infection with HHV-6 was confirmed in 12 (48%) of the 25 recipients. Four of the 12 developed skin rashes; three of these four had a febrile episode when the virus was isolated, whereas none of the remaining 13 developed the skin rash. These results suggest a frequent infection with HHV-6 only a few weeks after BMT and a close association between the infection with the virus and the development of skin rashes.

We performed cytogenetic studies in a patient with treatment-related acute leukemia (t-AL) to identify the associated chromosomal changes. Metaphase analysis revealed a t(3;21)(q26;q22) translocation. Acute promyelocytic leukemia (APL) had been diagnosed 4 years earlier and the patient had received intensive induction chemotherapy and sequential post-induction therapy that included agents that targeted DNA-topoisomerase II (topo II). This case suggests an association between previous therapy with topo II inhibitors and development of t-AL associated with a balanced aberration involving the 3q26 and 21q22 bands.

We evaluated the in vitro proliferative response to exogenous IL-1 beta in terms of tritiated thymidine (3H-TdR) incorporation in leukemic cells obtained from 119 patients with various types of acute leukemia. The content of IL-1 beta in leukemic cells was measured by enzyme-amplified sensitivity immunoassay. We observed a significant proliferative response to exogenous IL-1 beta in leukemic cells from 27/66 patients with de novo AML, 1/29 patients with ALL, 2/3 patients with AUL, 8/12 patients with AML arising from MDS, 4/7 patients with myeloid crisis of CML, and 0/4 patients with lymphoid crisis of CML. Proliferation was marked in myeloid leukemic cells of a more premature stem cell origin. There were no significant differences in proliferative responses among the different FAB classes of de novo AML. The IL-1 beta content of leukemic cells was low in patients with lymphoid leukemia, but there was no significant difference among the various types of myeloid leukemia. There was no correlation between the proliferative response to exogenous IL-1 beta and the IL-1 beta content of leukemic cells. When we correlated the proliferative response to exogenous IL-1 beta with treatment outcome in patients with de novo AML, we found the rate of complete remission (CR) to be lower in those with a high proliferative response. We noted a longer duration of CR (p = 0.07) and of survival (p0.05) in patients with a low proliferative response. Thus, a high proliferative response to IL-1 beta in the cells of AML patients may indicate a poor prognosis.