We have treated 38 transplant-eligible patients with relapsed/refractory non-Hodgkin's lymphoma and Hodgkin's disease using an outpatient-based regimen of ifosfamide, carboplatin and etoposide (ICE) for both salvage and peripheral blood stem cell mobilisation. Patients included relapsed or refractory diffuse large B-cell lymphoma (n = 17), follicular lymphoma (n = II), T-cell lymphoma (n = 2), mantle cell lymphoma (n = 2) and Hodgkin's disease (n = 6). Seven patients with diffuse large B-cell lymphoma and three patients with follicular lymphoma (26%) were considered chemorefractory. Cycles of ICE therapy were administered every 21 days as an outpatient and consisted of ifosfamide 5000 mg/m2 intravenously (i.v.) fractionated into three equally divided doses over 3 days, carboplatin [mg dose = 5 x area under the curve (AUC)] i.v. on day 1 and etoposide 100 mg/m2- i.v. daily for 3 days. Subsequently. granulocyte colony-stimulating factor (G-CSF)5 microg/kg subcutaneously (s.c.) was administered daily from day +5. Of the I I follicular lymphoma patients, 10 also received rituximab with ICE therapy. Median age of patients was 52 years (range 30-65). Patients received a mean of 2.6 cycles (range 1-4) of ICE. There were no toxic deaths and no significant non-haematological toxicities secondary to ICE therapy. Grade IV thrombocytopenia and grade IV neutropenia with at least one cycle of ICE were seen in 47% and 53% of patients, respectively. Median time to peripheral blood stem cell (PBSC) harvest was 14 days (range 10-20). while the median CD34+ cell yield was 5.2 x 10(6) cells/kg(range 2.3 x 10(6)-27.2 x 10(6)). Only one of the ICE-responders failed to mobilise PBSCs. The overall response rate to ICE was 87%. comprising 14 patients (37%) who achieved a complete response (CR) and 19 (50%) who achieved a partial response (PR). A total of 30 patients have undergone autologous stem cell transplantation(SCT) while two follicular lymphoma patients have received a non-myeloablative allogeneic SCT. Follow-up is short: however, the Kaplan-Meier estimate of the proportion of patients alive and event-free at a median follow-up of 11 months is 80% and 59%, respectively. Event-free survival for patients who achieved a CR after ICE and transplantation is 88% versus 45% for those who achieved a PR. These data confirm the efficacy and tolerability of fractionated ICE chemotherapy as both a salvage and mobilisation regimen that can be readily delivered in an outpatient setting.

We have treated 75 transplant-eligible patients with relapsed or refractory lymphoma using an outpatient-based fractionated regimen of ifosfamide, carboplatin and etoposide (ICE) for both salvage and stem cell mobilisation. Patients included DLBC (n = 33), follicular (n = 23), NK/T-cell (n = 3), mantle cell (n = 3) and Hodgkin's lymphoma (n = 13). Cycles of outpatient ICE were given every 21 days and consisted of: ifosfamide 5000 mg/m(2) i.v. fractionated into three equally divided doses and infused over 2-3 h on days 1-3, carboplatin (mg dose = 5 x AUC) i.v. over 1 h on day 1; and etoposide 100 mg/m(2) i.v. daily on days 1-3, plus filgrastim 5 microg/kg/day. Most patients with indolent lymphoma also received rituximab. The median age of patients was 52 years (range 26-69 years). Patients received a mean of 2.8 cycles of ICE. Non-haematological toxicities included grade 1/2 CNS toxicity in four patients, cardiac toxicity in two, reversible renal impairment and haematuria in one each. Haematological toxicity included grades III/IV thrombocytopenia and neutropenia with at least one cycle of ICE in 71% and 72% of patients, respectively. The median time to PBSC harvest was 14 days (range 10-20 days), while the median CD34(+) cell yield was 4.8 x 10(6)/kg (range 2.3-37.8). Five patients (7%) failed to mobilise PBSCs. The overall response rate to ICE was 89%, comprising 29% who achieved a CR and 60% who achieved a PR; for DLBCL, the overall response rate was 85% including 36% who achieved a CR and 49% who exhibited a PR. At a median follow-up of 24 months, the Kaplan-Meier estimates of the overall and event-free survival for all patients were 65% and 42%, respectively. For patients with DLBCL overall and event-free survival figures were 51% and 35%, respectively, at a median follow-up of 14 months. These data confirm the efficacy and tolerability of outpatient fractionated ICE as both a salvage and mobilisation regimen in relapsed/refractory lymphoma.

BackgroundClozapine is an atypical antipsychotic drug indicated for patients with schizophrenia in whom traditional antipsychotic drugs (such as haloperidol or the phenothiazines) are ineffective, or in those who experience intolerable adverse effects. Clozapine treatment may be complicated by the development of life­ threatening agranulocytosis, so regular haematological monitoring is required. ObjectivesTo determine the incidence of clozapine‐induced agranulocytosis in Australia and the importance of monitoring white blood cell counts in patients treated with clozapine. DesignReview of haematological monitoring tor the first three years (June 1993 ‐ July 1996) of operation of the Australian Clozaril (clozapine; Novartis Australia) Patient Monitoring System (CPMS) central database. ResultsIn the 4061 patients prospectively monitored by the CPMS, the incidence of agranulocytosis, neutropenia and leukopenia combined was 2.6% (n= 104); the incidence of agranulocytosis was 0.9% (n=37). So far there have been no deaths in Australia from the complications of clozapine‐induced agranulocytosis. ConclusionThe incidence of agranulocytosis and neutropenia associated with clozapine use in Australia is similar to that in the rest of the world. Monitoring the white blood cell counts of patients being treated with clozapine ensures minimal risk to patients who develop agranulocytosis.

Higher doses of the anthracycline daunorubicin during induction therapy for acute myeloid leukemia (AML) have been shown to improve remission rates and survival. We hypothesized that improvements in outcomes in adult AML may be further achieved by increased anthracycline dose during consolidation therapy. Patients and MethodsPatients with AML in complete remission after induction therapy were randomly assigned to receive two cycles of consolidation therapy with cytarabine 100 mg/m 2 daily for 5 days, etoposide 75 mg/m 2 daily for 5 days, and idarubicin 9 mg/m 2 daily for either 2 or 3 days (standard and intensive arms, respectively). The primary end point was leukemia-free survival (LFS). ResultsTwo hundred ninety-three patients 16 to 60 years of age, excluding those with core binding factor AML and acute promyelocytic leukemia, were randomly assigned to treatment groups (146 to the standard arm and 147 to the intensive arm). Both groups were balanced for age, karyotypic risk, and FLT3-internal tandem duplication and NPM1 gene mutations. One hundred twenty patients in the standard arm (82%) and 95 patients in the intensive arm (65%) completed planned consolidation (P , .001). Durations of severe neutropenia and thrombocytopenia were prolonged in the intensive arm, but there were no differences in serious nonhematological toxicities. With a median follow-up of 5.3 years (range, 0.6 to 9.9 years), there was a statistically significant improvement in LFS in the intensive arm compared with the standard arm (3-year LFS, 47% [95% CI, 40% to 56%] v 35% [95% CI, 28% to 44%]; P = .045). At 5 years, the overall survival rate was 57% in the intensive arm and 47% in the standard arm (P = .092). There was no evidence of selective benefit of intensive consolidation within the cytogenetic or FLT3-internal tandem duplication and NPM1 gene mutation subgroups. ConclusionAn increased cumulative dose of idarubicin during consolidation therapy for adult AML resulted in improved LFS, without increased nonhematologic toxicity. J Clin Oncol 35:1678-1685. © 2017 by American Society of Clinical Oncology INTRODUCTIONAnthracyclines are one of the major classes of drugs active against acute myeloid leukemia (AML).1 Daunorubicin used at 45 mg/m 2 daily for 3 days is an integral component of the 7 + 3 regimen, which, with various modifications, has been the standard induction regimen for AML for more than three decades.2 Increased daunorubicin dosage from 45 to 50 mg/m 2 to 90 mg/m 2 daily for 3 days during induction therapy for AML has been shown in three studies to improve remission rates and survival in some patient subgroups, although another trial showed no benefit of 90 mg/m 2 compared with 60 mg/m 2 , with the caveat that the lower-dose arm received a median cumulative total of 330 mg/m 2 daunorubicin. [3][4][5][6][7] Another anthracycline widely used for AML induction is idarubicin. Several randomized trials have now been conducted comparing idarubicin 12 mg/m 2 daily for 3 days with daunorubicin 45 to 50 mg/m 2 in the same schedule, ...

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Standard treatment for higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myeloid leukemia is azacitidine. In single arm studies, adding lenalidomide had been suggested to improve outcomes. The ALLG MDS4 phase II trial randomized such patients to standard azacitidine or combination azacitidine (75mg/m 2 /d days 1 to 5) with lenalidomide (10mg days 1–21 of 28-day cycle from cycle 3) to assess clinical benefit (alive without progressive disease) at 12 months. A total of 160 patients were enrolled; median age 70.7 years (range 42.5-87.2), 31.3% female with 14% chronic myelomonocytic leukemia, 12% acute myeloid leukemia and 74% myelodysplastic syndromes. Adverse events were similar in both arms. There was excellent delivery of protocol therapy (median azacitidine cycles 11 both arms) with few dose reductions, delays or early cessations. At median follow up 33.1 months (range 0.7-59.5), the rate of clinical benefit at 12 months was 65% azacitidine arm and 54% lenalidomide+azacitidine arm ( P =0.2). There was no difference in clinical benefit between each arm according to WHO diagnostic subgroup or IPSS-R. Overall response rate was 57% in azacitidine arm and 69% in lenalidomide+azacitidine ( P =0.14). There was no difference in progression- free or overall survival between the arms (each P >0.12). Although the combination of lenalidomide and azacitidine was tolerable, there was no improvement in clinical benefit, response rates or overall survival in higher risk myelodysplastic syndrome, chronic myelomonocytic leukemia or low blast acute myeloid leukemia patients compared to treatment with azacitidine alone. This trial was registered at www.anzc-tr.org.au as ACTRN12610000271000 .

Summary and conclusionsClinical records of 47 patients in whom spinal-cord compression was the presenting feature of plasma-cell myeloma were analysed retrospectively. Patients were referred during 1954-78. Median survival was 30 months and prognosis was best for those in whom the site of cord compression was the thoracic region. Early laminectomy and decompression followed by adequate radiotherapy resulted in complete or good partial response in over a third of patients who presented with complete paraplegia.Improvements in supportive care and more effective chemotherapy allow spinal-cord compression in myeloma to be treated promptly and vigorously, thus improving duration and quality of survival in a substantial proportion of patients. tntroduction Neurological complications of myeloma are relatively common,1 2 and include those associated with various metabolic disturbances,

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