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Remission induction of refractory anaemia with excess blasts in transformation by sole treatment with granulocyte colony-stimulating factor with persistent chromosomal abnormality.

We report a patient with myelodysplastic syndrome (MDS), refractory anaemia with excess blasts in transformation, in whom complete remission (CR) was achieved with the administration of granulocyte colony-stimulating factor (G-CSF). The 76-year-old patient was admitted to our hospital with a fever and a productive cough; a diagnosis of pneumonia was thus made. Following treatment with antibiotics, the patient's condition improved, and MDS was diagnosed from peripheral blood and bone marrow examinations after the patient recovered from the infection. The patient achieved a sustained haematological CR that was confirmed by morphological and flow cytometric examination after treatment with G-CSF alone, although chromosomal abnormalities persisted. According to the literature, in almost all patients with acute myeloid leukaemia or MDS who were reported to achieve CR by G-CSF, the course was associated with infection, although our case did not have this complication during the course of G-CSF therapy. We suggest that patients with G-CSF alone without infection can achieve CR and that this may be related to a differentiation effect of G-CSF based on persistent chromosomal abnormality in this case.

Aged↗

[Use of cyclosporin A for remission induction in newly-detected insulin-dependent diabetes].

It has been postulated that some of the recent-onset insulin-dependent diabetics, after the initial use of insulin therapy, might develop the "honey moon period", i.e., a spontaneous remission of the disease, defined as the state of normal metabolic control maintained without insulin therapy. However, it has also been shown that spontaneous remission appears only in 5% of the patients treated with conventional insulin therapy and lasts, most frequently, not more than a few weeks. Different therapeutic regimens of immunosuppression and immunomodulation have been used worldwide in order to induce the remission, based on the findings that an autoimmune process underlies the pathogenesis of this type of diabetes. In this study, we have shown the results of the follow-up analysis of the effects of the treatment with cyclosporin A in 21 recent-onset insulin-dependent diabetics. In 15 of those patients insulin treatment was applied as bi-daily doses of monocomponent insulin preparations, and in 6 of them intensified insulin therapy with human insulin was used. In the first group, the remission was achieved in 46.66% and in the second group in 66.66%, which is a significantly higher incidence than in control groups treated only with insulin, without cyclosporin. Moreover, the duration of remission was longer in the patients treated with cyclosporin. The analysis of the residual beta cell secretory capacity has shown that C-peptide levels (taken as a marker for insulin secretion) were slightly higher in patients with the spontaneous remission than in those with the cyclosporin-induced remission both in basal conditions and after stimulation with 1 mg of glucagon. In the patients with cyclosporin A-induced remission we found an improved basal C-peptide secretion and, even more, we detected a significant improvement in beta cell response to the glucagon stimulation. The analysis of the first-phase insulin secretory response (the insulin response to rapidly injected glucose during the intravenous glucose tolerance test) which has been shown to be impaired very early during the development of diabetes, has demonstrated the lack of its recovery both in the spontaneous and in cyclosporin A-induced remissions. The analysis of the molar insulin/C-peptide ratio has detected the impairments of this ratio which remains decreased both in spontaneous and cyclosporin-induced remissions.

C-Peptide↗

Seven day cytosine arabinoside administered subcutaneously plus daunorubicin for remission induction in AML.

51 patients (mean age 40, range 17-71) with previously untreated AML (25% of M4-6 FAB type) were given Ara-C subcutaneously 100 mg/m2 every 12 h for 7 days and DNR 45 mg/m2 on days 1-3 i.v. for inducing remission. After 52 days 49% of patients on an average reached CR. The complete responders were given a 5 day treatment pulses monthly until relapse, which consisted of Ara-C s.c. plus one of the following drugs added in cyclic rotation: 6-TG, cyclophosphamide, CCNU or DNR. After 2 years the intervals between cycles were prolonged step by step. The mean/median of CR duration equals 26/19 months and of the survival of complete responders 32.9/27 months. The relapse rate and the CNS relapse rate equaled 1.9% and 0.36% per patient/month of observation. T and B cell depletion was observed during maintenance. The results indicate that the subcutaneous route of administering Ara-C is effective during the induction of remission.

Adolescent↗

The use of glipizide combined with intensive insulin treatment for the induction of remissions in new onset adult type I diabetes.

To determine if glipizide could enhance remission induction in new onset type 1 diabetes compared to intensive insulin treatment alone, 27 patients with type 1 diabetes were intensively treated in an open randomized trial with subcutaneous injections for one month. The insulin was randomly either discontinued (Group A) or the insulin discontinued and glipizide begun (Group B) Three patients in Group A (22%) and 7 in Group B (54%, p < .05) underwent insulin-free remissions for 10.3 +/- 4.4 and 8.7 +/- 2.6 months, respectively (p = NS). Mean blood glucose levels during insulin treatment were lower in patients entering remissions (94 +/- 3 mg/dl versus 102 +/- 5 mg/dl, p < 0.05). C-peptide levels were performed 0, 4, 8, and 24 weeks after insulin treatment. When all patients were examined, mean stimulated C-peptide levels at 4 weeks (0.58 +/- 0.09 pm/ml) were increased compared to time 0 (0.32 +/- 0.05 pm/ml, p < 0.02). Patients not entering remission had higher 4-week stimulated values (0.67 +/- 0.12 pm/ml) compared to time 0 values (0.29 +/- 0.06 pm/ml, p < .01), whereas remission patients' mean C-peptide levels remained similar at 0, 4, 8 and 24 weeks. These data indicate that a) insulin treatment plus glipizide induces higher rates of remission compared to intensive insulin treatment alone, b) the intensity of initial metabolic control may be an important determinant for remission induction, and c) endogenous insulin secretion is not associated with remission induction, suggesting that glipizide alters insulin sensitivity or is immunomodulatory in the context of new onset type 1 diabetes.

Adult↗

DAE (daunorubicin, Ara-C, and etoposide) and intermediate dose Ara-C for remission induction and consolidation treatment of adult patients with acute myeloid leukemia.

Fifty-one patients (age 18-73 years) with acute myeloid leukemia were treated with daunorubicin, cytarabine, and etoposide in an age-adjusted protocol, with patients older than 50 receiving fewer days of therapy. Complete remission (CR) occurred in 66% of the patients (34 of 51 patients). Patients 50 years of age and younger achieved a 74% CR rate (23 of 31 patients) compared to a 55% CR rate (11 of 20 patients) in older patients. Of the 34 complete responders, 11 (32%) refused consolidation therapy and received traditional Chinese herbal medicine. All of these 11 patients relapsed after a short remission duration (median, 3.8 months) and died. The median remission duration and median overall survival of 23 complete responders receiving at least two courses of consolidation therapy were 10.1 and 19.8 months, respectively. The actuarial 3-year disease-free survival for these 23 complete responders was 21 +/- 9%. Myelosuppression was the major toxicity, and nonhematological side effects were acceptable. The regimen appeared to have acceptable toxicity, and its efficacy was comparable with that of standard regimens with long-term maintenance therapy.

Acute Disease↗

Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a Pediatric Oncology Group Study.

The relapse rate in childhood acute lymphoblastic leukemia (ALL) is approximately 30% but few reinduction regimens have investigated the intensive use of polyethylene glycol Escherichia coli asparaginase (PEG-Asp). Therefore, we assessed the pharmocokinetics and efficacy of PEG-Asp in this setting. Children with B-precursor ALL, in first marrow and/or extramedullary relapse were eligible. Reinduction included doxorubicin on day 1, prednisone for 28 days, vincristine weekly for 4 weeks, and PEG-Asp either weekly or biweekly by randomization. Asparaginase levels and antibody to both E coli asparaginase and PEG-asp were measured weekly just before each PEG-asp dose. Overall, 129 of 144 patients (pts) (90%) achieved a complete remission (CR). There was a highly significant difference in CR rates between weekly (69 of 71; 97%) and biweekly (60 of 73; 82%) PEG-Asp dosing (P =.003). Grade 3 or 4 infectious toxicity was common (50%), but only 4 pts died of sepsis during induction. Other toxicities were infrequent and hypersensitivity was rare (6 of 144; 4%). Low asparaginase levels were associated with high antibody titers to either native (P =.024) or PEG asp (P =.0013). The CR rate was significantly associated with higher levels of asparaginase (P =. 012). Patients with ALL in first relapse receiving weekly PEG-Asp had a higher rate of second remission compared with biweekly dosing. Low levels of asparaginase were associated with high antibody titers. Increased asparaginase levels may correlate with an improved CR rate. The use of intensive PEG-Asp should be explored further in the treatment of ALL. (Blood. 2000;96:1709-1715)

Adolescent↗

Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia.

Despite achieving complete remission with retinoic acid (RA), most patients with acute promyelocytic leukemia (APL) have minimal residual disease detectable by reverse transcription-PCR (RT-PCR) amplification. HuM195, a humanized monoclonal antibody reactive with the cell surface antigen CD33, specifically targets and kills myeloid leukemia cells. We studied whether HuM195 could eliminate minimal residual disease in patients with APL by using RT-PCR. After attaining clinical complete remission with RA and/or chemotherapy, patients received HuM195 twice weekly for 3 weeks. Patients in first remission were given consolidation chemotherapy, generally with three cycles of idarubicin and cytarabine. Patients in second or greater remission did not receive chemotherapy. All patients received six monthly courses of maintenance with two doses of HuM195. Twenty-five of 27 patients treated in first remission had positive RT-PCR determinations before HuM195 treatment. Of the 22 patients evaluable for conversion of positive RT-PCR assays, 11 (50%) became RT-PCR negative after HuM195 treatment without additional therapy. Within the subset of patients who received RA alone as induction, 8 of 18 evaluable patients (44%) had negative RT-PCR determinations after HuM195 treatment but before chemotherapy. Among similar patients treated on earlier studies, 7 of 34 patients (21%) induced into remission with RA and then maintained on the drug for 1 month were RT-PCR negative before chemotherapy (P = 0.07). Twenty-five of 27 patients with newly diagnosed APL (93%) remain in clinical complete remission for 7+ to 58+ months, with median follow-up of 29 months. Seven patients in second or third remission and one patient in molecular relapse were also treated. Only one of these patients became RT-PCR negative after treatment with HuM195. These data suggest that HuM195 has activity against minimal residual disease in APL, particularly in newly diagnosed patients.

Adolescent↗

[Auer rods-positive neutrophils observed at diagnosis increased after remission induction in patient with acute promyelocytic leukemia].

50-year-old male was admitted to our hospital because of gingival bleeding and fever in August 1987. The leukocyte count was 13,300/microliters with 80.5% leukemic promyelocytes and bone marrow was hypercellular with 86.4% leukemic promyelocytes. A small number of mature neutrophils containing Auer rods were seen in bone marrow. On a diagnosis of acute promyelocytic leukemia and treated with induction chemotherapy consisting of behenoyl-arabinofuranosyl cytosine (BHAC), daunorubicin, 6-mercaptopurine (6-MP) and prednisolone (PSL) was reformed. After cytoreduction, leukemic cells reappeared in the peripheral blood, concomitant with mature neutrophils having Auer rods. Vitamin D3 was not effective as a differentiation inducing agent. Complete remission was obtained in November 1987 by the reinduction chemotherapy consisting of BHAC, aclarubicin, 6-MP and PSL. In this case, neutrophils with Auer rods might have been derived from the leukemic clone and differentiation of leukemic promyelocytes by intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗