Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation.

BACKGROUND: Explore safety and efficacy of three palonosetron-containing regimens for emesis prevention over 7 days in multiple myeloma (MM) patients receiving melphalan (100 mg/m(2)) and hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Randomized, double-blind pilot study in MM patients (n=73) receiving 1, 2, or 3 days of 0.25 mg palonosetron (30-s i.v. bolus) 30 min before melphalan (days -2 and -1) and HSCT (day 0). Patients received dexamethasone (20 mg i.v., days -2 and -1) immediately before or after study drug/placebo. Daily diaries recorded emesis, rescue medication, nausea duration, and adverse events (AEs). RESULTS: Seven-day complete protection (no emesis) occurred in 41.7% [95% confidence interval (CI) 22.1% to 63.4%], 41.7% (95% CI 22.1% to 63.4%), and 44.0% (95% CI 24.2% to 65.1%) of patients receiving 1, 2, or 3 days of palonosetron, respectively (P=0.43). Complete response (emesis free without rescue medication) occurred in 8.3%, 20.8%, and 20.0% (P=0.14). Common AEs (≥10%) were mild-to-moderate diarrhea, constipation, headache, insomnia, and flatulence. No serious AEs occurred. CONCLUSIONS: Palonosetron with dexamethasone was safe and effective in preventing emesis in MM patients receiving melphalan and HSCT. This pilot study with a limited number of patients suggests that multiple doses of palonosetron could be more effective than a single dose in making patients emesis free without need for rescue medication. However, even multiple doses of palonosetron resulted in only 20% of patients being emesis free without rescue medication, suggesting that further improvement will require development of more effective combination antiemetic therapy.

Phaeodarian skeletons: their role in silica transport to the deep sea.

The skeletons of phaeodarian Radiolaria transport and redistribute silica to the tropical deep oceans by dissolving in the water column and on the sea floor. The skeletons are initially solid but within a few days to months become progressively more porous while settling through the water column. Phaeodarian Radiolaria are rarely preserved in the bottom sediments; in contrast, polycystine Radiolaria are the dominant Radiolaria preserved in the fossil record. This preservational difference may be due to differences in skeletal constituents.

Variable porosity in siliceous skeletons: determination and importance.

Gas adsorption data were used to obtain the specific surface area and specific pore volume for a variety of biogenically precipitated silica semples. The results suggest that this material is finely divided and porous. This interpretation was corroborated by the use of transmission electron microscopy at magnifications up to 180,000.

Autologous transplantation in elderly patients with multiple myeloma: are we asking the right questions?

Multiple myeloma is a disease of the elderly. Survival outcomes remain unacceptably low in older adults with multiple myeloma. To date, no obvious difference in tumor biology has been elucidated to explain the survival disparity between older and younger patients. Multiple factors including comorbidity, performance status, decreased physiologic reserve and potentially undertreatment contribute to poor outcomes in elderly patients with multiple myeloma. High-dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly being used to treat elderly patients with multiple myeloma in an effort to improve survival outcomes. Recent case comparison studies, and preliminary transplant registry data suggest that selected older patients can be treated with high-dose chemotherapy effectively with similar toxicity and survival benefits compared to younger patients. Traditional upper age limits for autologous transplantation are being challenged along with the definition of 'elderly' itself. Ultimately, the role of high-dose chemotherapy with stem cell rescue in the upfront treatment of older adults with multiple myeloma can only be established by prospective randomized trials. In the process of designing studies to investigate the use of ASCT in older patients, multiple issues unique to the elderly population will need to be considered. First, it will be critical to develop and validate patient selection algorithms that incorporate measures of comorbidity, cognitive function, physiologic reserve and psychosocial function to identify patients most likely to tolerate and benefit from ASCT. Second, preparative and conditioning regimens will need to be further tailored to maximize the benefit to risk ratio. Finally, outcome measures in clinical trials should include disability and quality of life measures, which may be equally important in making treatment decisions for older patients. The future application and study of autologous transplantation in older patients with multiple myeloma provides a unique opportunity to challenge ageism and serve as a model for development of tailored assessments and interventions in this population.

Correlations between immunological phenotype and karyotype in malignant lymphoma.

We have correlated immunological characteristics and karyotypic abnormalities from lymphomas in 118 patients. T-lymphomas differed significantly from B- and non-B-, non-T-lymphomas in having more normal metaphases, trisomy 19, and breaks at 1q21, 2q21, 3q27, 4q21, and 17q21 (P less than or equal to 0.03). Non-T-lymphomas had breaks in 18q in one-half the cases, but only one of 11 T-lymphomas had such breaks (P = 0.02). Among B-lymphomas, specific chromosome abnormalities were associated with the type of immunoglobulin heavy but not light chain expressed. A break at 14q22 or q24 was associated with surface delta mu-immunoglobulin (P = 0.02); trisomy 22 or a break in 22q and a break at 2q32 was associated with surface gamma-immunoglobulin (P less than 0.001); and trisomy 12 and a break at 2p13 was associated with cytoplasmic gamma-immunoglobulin (P less than 0.01). Among B-lymphomas, several cytogenetic abnormalities were associated (P less than or equal to 0.02) with expression of CD24 or CD9 surface antigens. Lack of CD24 was associated with breaks in 2p25, 5q, and 6q21; CD9 was associated with a break at 6q15. Associations with a specific immunological phenotype were not identified for cytogenetic abnormalities involving a band to which genes encoding immunoglobulin or the T-cell receptor have been localized. Breaks were common at 14q32, the genomic site of the immunoglobulin heavy chain loci, in B-, non-B-, non-T-, and T-lymphomas. In T-lymphomas this may be because this is the site of the AKT1 oncogene. Breaks were uncommonly found at the light chain loci or the genomic sites encoding the T-cell receptor. However, the recurring breakpoints associated with T-lymphomas were commonly found on chromosomes to which genes coding for various T-cell antigens have recently been provisionally assigned.

Therapy of chronic myelogenous leukemia with allogeneic bone marrow transplantation.

From December 1982 to January 1986, 57 patients received allogeneic bone marrow transplantation as therapy for Philadelphia chromosome (Ph') positive chronic myelogenous leukemia (CML). All patients were prepared for transplantation with cyclophosphamide 60 mg/kg (day -6, -5) and fractionated total body irradiation, 165 cGy twice daily (day -4, -3, -2, -1) and received major histocompatibility (MHC) matched donor marrow (day 0). All patients received graft-v-host disease (GVHD) prophylaxis with methotrexate, prednisone, and either antithymocyte globulin (ATG) (55 patients) or OKT3 infusion (two patients). The projected survival of 29 chronic phase patients is 64% (95% confidence interval [Cl] 42% to 86%); and of 28 accelerated phase patients, 30% (95% Cl, 12% to 48%) at 30 months (P = .005). Multivariate regression analysis of pretransplant patient characteristics demonstrated that the presence of chronic phase and age less than 30 years were the only prognostic features studied that independently predicted survival. No evidence of persistent or recurrent disease has occurred in chronic phase patients; however, reappearance of the Ph' was observed in seven accelerated-phase patients, and hematologic relapse occurred in three of these seven patients. The incidence of grade II to IV acute GVHD is 63% (95% Cl, 50% to 76%) at 100 days, and that of extensive chronic GVHD is 53% (95% Cl, 33% to 74%) at 30 months. The median Karnofsky activity assessment of survivors is 100% (range, 60% to 100%), and all activity assessments less than 100% can be attributed to complications of GVHD. Bone marrow transplantation therapy for CML after preparation with cyclophosphamide and fractionated total body irradiation results in a high proportion of disease-free survival in chronic-phase patients. Survival in accelerated phase is significantly worse and is associated with relapse. GVHD has emerged as a significant cause of morbidity and mortality in this study.

Allogeneic bone marrow transplantation for acute lymphoblastic leukemia in remission: prolonged survival associated with acute graft-versus-host disease.

Forty remission patients with high-risk acute lymphoblastic leukemia (ALL) underwent matched allogenic bone marrow transplantation (BMT) following preparation with cyclophosphamide and fractionated total body irradiation (TBI). As of March 1987, the median follow-up is more than 3 1/2 years. Thirteen patients are alive (11 relapse free) between 2 and 4 1/2 years post-BMT. Neither age, sex, remission number, prior extramedullary leukemia, nor WBC at diagnosis of ALL was statistically significant as a predictor of relapse-free survival. The development of acute graft-v-host disease (GVHD) in 17 patients was found, with time-dependent Cox regression analysis, to be associated with a significant reduction in post-BMT relapse risk (P = .04) and improved disease-free survival (P = .11). A prospective, randomized trial of maintenance chemotherapy with oral methotrexate and mercaptopurine did not demonstrate improvement in relapse risk or survival for those assigned maintenance chemotherapy (P = .7). These results suggest that allogeneic BMT can result in extended relapse-free survival for some patients with high-risk ALL. More effective preparative chemoradiotherapy and exploitation of the apparent graft-v-leukemia effect may be useful in future trials.

Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer.

Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while eight of nine patients at 225 mg/m2 were affected (p less than 0.005). Administration of cyclophosphamide (300 mg/m2 IV) 1 week before melphalan therapy did not reduce the incidence of severe gastrointestinal toxicity. Plasma melphalan concentration peaked 30-60 min after infusion (4.8-11.5 micrograms/mL) but declined rapidly. Cerebrospinal fluid concentration was 10% of the corresponding plasma concentration and was undetectable at 3 hours. Antitumor responses occurred in nine of 13 patients with malignant melanoma (five complete and four partial remissions), and ranged 2-12+ months with a median of 5 months. Four of six neuroblastomas demonstrated responses (three complete and one partial remission( lasting a median of 7.5 (range: 5-10) months. Other tumors in which this regimen had activity included breast cancer and Ewing's sarcoma. The overall response rate for the 33 patients was 30% complete remissions (10 patients) and 21% partial remissions (seven patients). High dose melphalan and autologous bone marrow transplantation is a promising therapy for patients with malignancies for which no effective treatment is known or for patients whose cancer is refractory to conventional therapeutic agents.

High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma.

PURPOSE: Women with locally unresectable and inflammatory breast carcinoma (IBC) have an approximately 30% 5-year disease-free survival (DFS) rate with conventional multimodality therapy. A short but dose-intensive multimodality phase II trial was designed in an attempt to improve outcome in stage IIIB disease. Mastectomy was performed after high-dose therapy to evaluate pathologic response to treatment. METHODS: Women with newly diagnosed disease received four 2-week cycles of doxorubicin 90 mg/m2 with granulocyte colony-stimulating factor (G-CSF), followed by cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) with marrow and peripheral-blood progenitor cell (PBPC) support. Local therapy consisted of mastectomy and radiotherapy. Tamoxifen (5 years) was begun if the patient was estrogen receptor-positive (ER+). RESULTS: Fifty women (46 stage IIIB [91% IBC], four stage IIIA) entered the study and 47 are assessable. Ten had mastectomy before any systemic therapy (seven with pathologic IBC, three with residual tumor after mastectomy). Eighty percent received full-dose doxorubicin with 60% on schedule. Clinical response rates to induction were 15% complete response (CR), 5% very good partial response (VGPR), 59% partial response (PR), and 21% minor response (MR)/stable disease (SD). Mastectomy after CTCb in 37 patients showed a 14% pathologic CR rate, 29% microscopic foci in breast and/or axilla, and 57% gross tumor. Fifteen (32%) patients have relapsed (median, 17 months post-CTCb). The 30-month DFS is estimated at 64%. For those in pathologic CR, with microscopic, or with gross disease remaining after CTCb, the 30-month DFS is estimated at 100%, 70%, and 38%, respectively. Those with zero, one to three, or > or = four positive nodes at axillary dissection had a median DFS of 31, 18, and 13 months, respectively. CONCLUSION: This short but dose-intensive multimodality approach for stage IIIB breast carcinoma is feasible with encouraging results to date.

Repetitive cycles of cyclophosphamide, thiotepa, and carboplatin intensification with peripheral-blood progenitor cells and filgrastim in advanced breast cancer patients.

PURPOSE: As an alternative to single-cycle cyclophosphamide, thiotepa, and carboplatin (CTCb) intensification, we evaluated the feasibility of administering one-quarter dose CTCb for four cycles with peripheral-blood progenitor-cell (PBPC) and filgrastim (granulocyte colony-stimulating factor [G-CSF]) in advanced-stage breast cancer patients. PATIENTS AND METHODS: From June 1992 to August 1993, 20 stage IIIB (n = 7) and IV (n = 13) breast cancer patients received 78 cycles of induction with doxorubicin 90 mg/m2 by intravenous (IV) bolus with G-CSF 5 microg/kg/d by subcutaneous injection (SC) repeated every 14 to 21 days for four cycles. PBPC were collected by 2-hour single-blood volume leukapheresis on 2 consecutive days at the time of hematologic recovery from each cycle of doxorubicin. Eighteen patients received 61 cycles of intensification with cyclophosphamide 1,500 mg/m2, thiotepa 125 mg/m2, and carboplatin 200 mg/m2 by IV continuous infusion with G-CSF 10 microg/kg/d SC and PBPC support repeated every 21 to 42 days for four cycles. RESULTS: Twelve of 20 patients (60%) completed all four planned cycles of doxorubicin induction followed by four cycles of one-quarter dose CTCb intensification. Statistically significantly decreases in the yield of mononuclear cells (MNC) (median slope per day, -0.032; P = .03), granulocyte-macrophage colony-forming unit (CFU-GM) (median slope per day, -0.57; P = .0008), and burst-forming unit-erythroid (BFU-E) (median slope per day, -1.18; P = .006) were observed over the course of the eight leukaphereses. Of 18 patients who began CTCb, 12 (67%) completed four cycles. Six patients were removed from study during intensification: two for progressive disease (PD), one refused further treatment, and three for dose-limiting hematologic toxicity. A fourth patient fulfilled the criteria for dose-limiting hematologic toxicity after cycle 4. The toxicity of the multiple cycle CTCb intensification regimen consisted of grade IV leukopenia, grade IV thrombocytopenia, and febrile neutropenia in 100%, 100%, and 26% of cycles, respectively. The median duration of each CTCb cycle was 24 days (range, 18 to 63), and the median duration of an absolute neutrophil count (ANC) < or = 500/microL and platelet count < or = 20,000/microL during each cycle was 6 days (range, 2 to 15) and 4 days (range, 0 to 38), respectively. CONCLUSION: It is feasible to administer repetitive cycles of one-quarter dose CTCb intensification with PBPC and G-CSF. Additional studies are required to determine whether multiple cycles of CTCb intensification might offer a therapeutic advantage over a single high-dose cycle.

Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease.

PURPOSE: To determine the outcome of HLA-identical sibling bone marrow transplants in advanced Hodgkin's disease. PATIENTS AND METHODS: We reviewed the data on 100 consecutive patients with Hodgkin's disease who received HLA-identical sibling bone marrow transplants between April 1, 1982 and August 12, 1992, reported to the International Bone Marrow Transplant Registry (IBMTR). The median interval from diagnosis to transplant was 2.5 years (range, < 1 to 14). All had advanced disease. Eighty-nine of 100 patients were not in remission at the time of transplant. Fifty had pretransplant Karnofsky scores less than 90% and 27 had active infection in the week before transplant. Patients received a variety of conditioning regimens; 45 received total-body radiation. RESULTS: The 100-day probability of acute graft-versus-host disease (GVHD) was 35% (95% confidence interval [CI], 26% to 46%); the 3-year probability of chronic GVHD was 45% (95% CI, 31% to 59%). The 3-year probability of relapse was 65% (95% CI, 50% to 78%). The 3-year probability of survival was 21% (95% CI, 14% to 30%). The 3-year disease-free survival rate was 15% (95% CI, 9% to 24%). CONCLUSION: HLA-identical sibling bone marrow transplants have a limited role in advanced Hodgkin's disease.

Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in Drosophila.

Previous work has shown that mutation of the gene that encodes the microtubule motor subunit kinesin heavy chain (Khc) in Drosophila inhibits neuronal sodium channel activity, action potentials and neurotransmitter secretion. These physiological defects cause progressive distal paralysis in larvae. To identify the cellular defects that cause these phenotypes, larval nerves were studied by light and electron microscopy. The axons of Khc mutants develop dramatic focal swellings along their lengths. The swellings are packed with fast axonal transport cargoes including vesicles, synaptic membrane proteins, mitochondria and prelysosomal organelles, but not with slow axonal transport cargoes such as cytoskeletal elements. Khc mutations also impair the development of larval motor axon terminals, causing dystrophic morphology and marked reductions in synaptic bouton numbers. These observations suggest that as the concentration of maternally provided wild-type KHC decreases, axonal organelles transported by kinesin periodically stall. This causes organelle jams that disrupt retrograde as well as anterograde fast axonal transport, leading to defective action potentials, dystrophic terminals, reduced transmitter secretion and progressive distal paralysis. These phenotypes parallel the pathologies of some vertebrate motor neuron diseases, including some forms of amyotrophic lateral sclerosis (ALS), and suggest that impaired fast axonal transport is a key element in these diseases.

Mutation of the axonal transport motor kinesin enhances paralytic and suppresses Shaker in Drosophila.

To investigate the possibility that kinesin transports vesicles bearing proteins essential for ion channel activity, the effects of kinesin (Khc) and ion channel mutations were compared in Drosophila using established tests. Our results show that Khc mutations produce defects and genetic interactions characteristic of paralytic (para) and maleless (mle) mutations that cause reduced expression or function of the alpha-subunit of voltage-gated sodium channels. Like para and mle mutations, Khc mutations cause temperature-sensitive (TS) paralysis. When combined with para or mle mutations, Khe mutations cause synthetic lethality and a synergistic enhancement of TS-paralysis. Furthermore, Khc: mutations suppress Shaker and ether-a-go-go mutations that disrupt potassium channel activity. In light of previous physiological tests that show that Khc mutations inhibit compound action potential propagation in segmental nerves, these data indicate that kinesin activity is required for normal inward sodium currents during neuronal action potentials. Tests for phenotypic similarities and genetic interactions between kinesin and sodium/potassium ATPse mutations suggest that impaired kinesin function does not affect the driving force on sodium ions. We hypothesize that a loss of kinesin function inhibits the anterograde axonal transport of vesicles bearing sodium channels.

Economic analysis of unrelated allogeneic bone marrow transplantation: results from the randomized clinical trial of T-cell depletion vs unmanipulated grafts for the prevention of graft-versus-host disease.

Unrelated-donor marrow transplantation is a potential option for transplant candidates lacking a compatible related donor. The T-cell Depletion Study compared the 3-year disease-free survival for patients receiving T-cell-depleted (TCD) donor marrow (n = 203) vs unmanipulated donor marrow with methotrexate and cyclosporine (M/C) (n = 207). Hospital costs during index admission were documented with billing data, while hospital costs during subsequent 6-month follow-up were estimated from case report forms. Patients with index admission billing were included in the analysis (TCD = 119, M/C = 127). Total hospital length of stay (LOS) was similar across groups, with medians 47.0 days for TCD and 52.0 days for M/C (P = 0.72). Total hospital costs were comparable, 145,115 dollars vs 141,981 dollars (P = 0.63) for TCD and M/C, respectively. However, controlling for site and patient characteristics, TCD was associated with a 12.1% reduction in LOS for the index admission (95% CI -19.4%, -4.3%). Independent of treatment, HLA matching (6/6) was associated with an 8.6% (95% CI -17.4%, +1.2%) reduction in the index admission LOS, while cost was lower by 15.8% (95% CI -26.7%, -3.3%). Treatment costs were similar for TCD and M/C study groups. Savings on reduced cost for treating acute graft-versus-host disease were likely offset by increase in serious infections in the TCD arm.

Phase I study of continuous infusion 6-thioguanine in patients with acute leukemia.

6-Thioguanine (6-TG) was administered as a continuous i.v. infusion for 7 days to 24 patients with relapsed or refractory acute leukemia or in the blast phase of chronic granulocytic leukemia. The daily dose of 6-TG was escalated from 37.5 mg/m2 to 160 mg/m2. Stomatitis was dose-related and dose-limiting with a maximum tolerated dose of 120 mg/m2 daily. Cutaneous reactions were dose-related but not dose-limiting. The recommended dose for phase II trials in acute leukemia is 120 mg/m2 per day as a continuous infusion for 7 days. There were two complete and four partial remissions among all patients. At the suggested phase II dose of 120 mg/m2 there were two complete remissions and one partial remission in five evaluable patients.

Phase I clinical trial of serotherapy in patients with acute myeloid leukemia with an immunoglobulin M monoclonal antibody to CD15.

Sixteen patients with acute myeloid leukemia (AML) were treated with a continuous i.v. infusion of mAb PM-81, an IgM mAb directed against the cellular differentiation antigen CD15, which is expressed on leukemia cells of >95% of patients with AML. MAb PM-81, also referred to as MDX-11, is capable of activating human and rabbit complement and lysing CD15-positive AML cells. In this Phase I study, patients were treated with 0.5, 1.0, or 1.5 mg/kg MDX-11 delivered over a 24-h period followed by conventional chemotherapy. Transient decreases in circulating blast cells postinfusion (prior to chemotherapy) were observed at all doses. We were able to show MDX-11 binding to bone marrow blasts in those patients who achieved stable serum levels of MDX-11. Serum MDX-11 was detectable at the 1. 0- and 1.5-mg/kg doses. Doses of 0.5 and 1.0 mg/kg were generally well tolerated, with no toxicities greater than grade II (Eastern Cooperative Oncology Group) reported. However, two of five patients receiving the 1.5-mg/kg dose experienced grade IV toxicities that resolved with treatment (one of these patients completed the infusion). Common toxicities reported included fever, chills, and hypotension. Only one patient developed human antimouse antibodies at 4 weeks posttreatment. This study determined that 1.0 mg/kg is a biologically effective dose that can be administered safely with little toxicity. Based on these results, we are pursuing a Phase I/II study of MDX-11 infusion following chemotherapy for patients with relapsed AML.

Randomized, comparative study of high-dose (with autologous bone marrow support) versus low-dose cyclophosphamide, cisplatin, and carmustine as consolidation to adjuvant cyclophosphamide, doxorubicin, and fluorouracil for patients with operable stage II or III breast cancer involving 10 or more axillary lymph nodes (CALGB Protocol 9082). Cancer and Leukemia Group B.

The prognosis for patients with primary breast cancer involving multiple axillary lymph nodes is poor. Only about 30% of patients remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy, and radiation therapy. In nonrandomized studies, the use of high-dose chemotherapy as consolidation therapy after standard-dose induction chemotherapy has resulted in an apparent improvement in disease-free survival rates to over 70%. These results have prompted the National Cancer Institute to sponsor large-scale, multicenter, randomized comparative trials of this strategy. This Intergroup Study (Cancer and Leukemia Group B 9082, Southwest Oncology Group 9114, and National Cancer Institute of Canada MA13) compares two treatment strategies in women with primary breast cancer involving 10 or more axillary lymph nodes. Arms A and B are identical in the use of four cycles of conventional therapy with cyclophosphamide and doxorubicin and fluorouracil, radiation therapy, and tamoxifen. The only difference between the two arms is the dose intensity of the cyclophosphamide, cisplatin, and carmustine given following conventional adjuvant treatment. Arm A dictates bone marrow, peripheral blood stem cell, and hematopoietic growth factor support and frequently requires a prolonged hospital stay with high resource utilization. Arm B, with its less dose-intensive therapy, requires considerably less support to apply the treatment. Because of the high cost of this therapy and the requirement for technology-intensive support, there has been considerable interest in economic outcome assessments.

Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.

Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients.

Invasive Scopulariopsis in the immunocompromised host.

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.

Invasive Fusarium infections in bone marrow transplant recipients.

From November 1982 to September 1983, three cases of invasive infection due to Fusarium species were documented in bone marrow transplant recipients. Fusarium was cultured from discrete skin nodules (one patient), maxillary sinus (one patient), or from the blood and surgically excised nasal septum (one patient). All three isolates were resistant to 5-fluorocytosine, whereas only one isolate was resistant to amphotericin B. Although all three patients died, two of the patients had clearing of their Fusarium infection. From this experience and from a review of the literature, it is concluded that despite the dismal prognosis for immunocompromised patients with Fusarium, beneficial therapies would include systemic amphotericin B, local surgical resection, and possibly leukocyte transfusions.