Shozo Yokomaku

Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia.

Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.

Treatment of plasma cell neoplasm with recombinant leukocyte A interferon and human lymphoblastoid interferon

SummaryThisty cases of plasma cell neoplasms (24 multiple myeloma, one plasma cell leukemia, and three primary macroglobulinemia) were treated with two kinds of highly purified α-interferons, recombinant human leukocyte interferon (rIFN-αA) (16 cases) and human lymphoblastoid interferon (HLBI) (14 cases). Partial remission (PR) was obtained in two of 16 evaluable cases treated with rIFN-αA and in two of 12 evaluable cases treated with HLBI. If minor response (MR) was included, responses were observed in seven (31.3%) and six (50%), respectively. Response (PR+MR) was noted in 38% of 21 previously treated patients and 71% of seven previously untreated patients. Side-effects were noted in more than two-thirds of the patients. They included fever, malaise, nausea/anorexia and myelosuppression. Thus, these two kinds of highly purified α-interferon were effective in plama cell neoplasm, producing unequivocal response in 14.3% of the cases without unacceptable side-effects.

Randomized controlled study of chemoimmunotherapy of acute myelogenous leukemia (AML) in adults with Nocardia Rubra cell‐wall skeleton and irradiated allogeneic AML cells

The effect of immunotherapy with Nocardia rubra cell‐wall skeleton (N‐CWS) on remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and having been consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N‐CWS and irradiated allogeneic AML cells. Thirty‐four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (P = 0.080) and on survival length (P = 0.098). When the data were analyzed at 30 months after the entry, there was a borderline significant difference in remission duration (P = 0.080) between the two groups, prolonging the 50% remission period by 110 days; but no significant difference in survival length (P = 0.314), although the 50% survival was 168 days longer in the chemoimmunotherapy group. However, there were 4 (18.2%) 5‐year relapse‐free survivors among 22 patients (11 in each group) who had been diagnosed more than 5 years before the time of the present analysis, and all of them belonged to the chemoimmunotherapy group (P = 0.090). Thus, immunotherapy with N‐CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy. Cancer 57:1483–1488, 1986.

Intensive Induction Therapy with Behenoyl, Cytosine Arabinoside, Daunorubicin, and 6-Mercaptopurine Followed by Intensive Consolidation with Mitoxantrone, Etoposide, Vincristine, and Intermediate-Dose Continuous Cytarabine (M-85 Protocol) for Adult Acute Myelogenous Leukemia

Over 70% of adults with acute myelogenous leukemia (AML) are induced into complete remission (CR) [1-4]. Our current target is not only to increase the remission rate, but to increase the cure rate of this disease, hopefully to over 50%. Two previous protocols for adult AML in our hospitals, BHACDMP [2] and BHAC-DMP (II) [4], from 1979 to 1985 showed that the percentage of blasts in the bone marrow at 2 weeks after the start of therapy is the most significant prognostic factor for predicting longer continuing CR by a multivariate analysis. However, in BHAC-DMP (II), where we gave very intensive induction therapy to reduce blasts in the marrows as quickly as possible, we were forced to stop this protocol because of a high incidence of severe infections, especially aspergillosis and other fungal infections, owing to prolonged myelosuppression during the induction period.