Randomized, double-blind, multicenter trial comparing clinafloxacin with imipenem as empirical monotherapy for febrile granulocytopenic patients.

In a double-blind, multicenter trial, 541 febrile granulocytopenic patients were randomized to receive either intravenous (iv) clinafloxacin (200 mg every 12 h) or i.v. imipenem (500 mg every 6 h) as empirical monotherapy. More baseline pathogens were susceptible to clinafloxacin (259 [99%] of 262 organisms) than to imipenem (253 [95%] of 265; P=.03). Initial favorable clinical response rates for clinafloxacin (88 [32%] of 272 patients) and imipenem (89 [33%] of 269) were similar. After addition of other antimicrobial agents, overall response rates were 259 (95%) of 272 for clinafloxacin and 251 (93%) of 269 for imipenem. During the study, only 13 clinafloxacin (5%) and 18 imipenem (7%) recipients died. Both drugs were generally well tolerated. Drug-related skin rash occurred more often with clinafloxacin (11% vs. 6%; P=.07), whereas nausea (2% vs. 5%; P=.16), Clostridium-difficile-associated diarrhea (3% vs. 8%; P=.02), and seizures (0% vs. 2%; P=.06) occurred more often with imipenem. These results suggest that clinafloxacin and imipenem have similar efficacy as empirical monotherapy in febrile granulocytopenic patients.

Determination and validation of a predictive model for Clostridium difficile diarrhea in hospitalized oncology patients.

BACKGROUND: Clostridium difficile colitis in the cancer patient receiving chemotherapy is a frequent cause of morbidity which may prolong hospitalization. Techniques for identifying infection often delay the initiation of therapy. PATIENTS AND METHODS: In this retrospective case-control analysis, we identified predictors for C. difficile-associated diarrhea in 29 patients hospitalized from 1988 to 1993 on a hematologic malignancy/bone marrow transplant unit (hospital A). We then validated our model with 58 C. difficile cases and 74 controls admitted to an oncology unit from a different institution (hospital B). RESULTS: We found that low intensity of chemotherapy (P < 0.001), lack of parenteral vancomycin use (P = 0.03) and hospitalization within the past two months (P = 0.05) were independently predictive of C. difficile colitis by multivariate analysis. These variables were weighted for predictive capability using a receiver operator characteristic score; low intensity chemotherapy was assigned two points, lack of parenteral vancomycin received one point and prior hospitalization one point (P < 0.001 by chi 2 for trend). The receiver operating characteristic (ROC) curve areas were 0.78 for patients at hospital A and 0.70 at hospital B indicating moderate drop off in discrimination. Compared to hospital A patients, hospital B patients hospitalized between 1989 and 1994 were more often women (P = 0.04), received less systemic vancomycin (P = 0.01), were less frequently neutropenic (P < 0.05), and received less intense chemotherapy regimens (P < 0.05). Despite these differences in demographics in patients between these institutions, our predictive model was validated in hospital B patients (P = 0.02 by chi 2 for trend). CONCLUSIONS: The results of this study may help clinicians predict the risk of C. difficile disease in the hospitalized immunocompromised oncology patient and may help guide empiric therapy while awaiting results of stool toxin assays.

Open randomized study of cefepime versus piperacillin-gentamicin for treatment of febrile neutropenic cancer patients.

An open-label randomized trial comparing the efficacy and safety of cefepime versus piperacillin plus gentamicin (P+G) given intravenously for the treatment of febrile episodes in neutropenic patients with underlying malignancy was conducted at two oncology centers. Over a 30-month period 111 patients were enrolled and 99 patients were found to be suitable for evaluation. At the 72-h time of evaluation, cefepime monotherapy and P+G combination therapy produced comparable clinical response rates (78% for both). P+G and cefepime produced comparable response rates in microbiologically documented (78 versus 71%), clinically documented (100 versus 100%), and possible (75 versus 79%) infections. The P+G and cefepime treatments achieved comparable microbiological eradication of gram-negative (100 versus 71%) (P = 0.09) and gram-positive (44 versus 70%) (P = 0.37) organisms. There were no statistically significant differences in the rates of superinfection between the groups; however, more superinfections of fungal origin were noted in the P+G group. Cefepime was demonstrated to be an effective and safe treatment for febrile episodes in neutropenic patients with malignancies, and its lack of nephrotoxicity compared to P+G was noteworthy. Cefepime appears to be a candidate for monotherapy in febrile neutropenic cancer patients.

Overview by an oncologist: what are the imaging needs of the oncologist and oncological surgeon?

Imaging techniques play an important role in the management of the care of the patient who has suspected or known malignancy. Currently available tests have high sensitivity, but low specificity and high false-positive rates. For example, computed tomography scanning and magnetic resonance imaging provide sensitive cross sectional imaging and have improved the detection of small lesions without increasing etiologic specificity. Many masses cannot be further characterized with current imaging studies which may be a particular problem in the assessment of residual disease versus fibrosis. Often, results of these imaging studies create new problems and confusion that require additional tests and sometimes invasive approaches in order to obtain definite answers. Clearly, the oncologist and oncological surgeon need new screening tests with increased specificity without losing sensitivity for most common cancers, and new imaging techniques for staging and follow-up of very small volume tumors without sacrificing specificity. New nuclear medicine techniques such as positron emission tomography (PET) scan or immunoscintigraphy may provide a functional evaluation of a tumor for screening, staging, and follow-up. Initial results of immunoscintigraphy and PET imaging are very encouraging. They may in the future provide prognostic evaluation addition to anatomical assessment of tumor. Additionally, these new imaging studies survey the entire body and detect metastases at multiple sites (regional and distal) simultaneously. Therefore, we should determine the role of these imaging techniques in carefully controlled prospective trials.

Paecilomyces sinusitis in an immunocompromised adult patient: case report and review.

A case of fungal sinusitis caused by Paecilomyces lilacinus that was unresponsive to amphotericin B and involved a patient with acute myeloid leukemia is described. Histologic examination of sinus tissue and periorbital bone demonstrated invasion by a fungus with septate hyphae, which was identified in culture as P. lilacinus. The isolate was resistant to amphotericin B but susceptible to itraconazole. The patient responded clinically when itraconazole was added to the treatment regimen. Invasive aspergilar infections are frequently diagnosed by histology. Other fungi such as Fusarium, Pseudallescheria, and Paecilomyces species also produce hyphae in tissue and can be confused with Aspergillus species. However, these pathogens may be resistant to amphotericin B. Since alternative therapy is now available for infections with some of the amphotericin B-resistant fungi, such as P. lilacinus, every effort should be made to recover the fungal pathogen so that effective treatment can be administered.

Cefoperazone/sulbactam versus cefoperazone plus mezlocillin: empiric therapy for febrile, neutropenic bone marrow transplant patients.

We conducted a prospective, randomized trial in 132 patients undergoing bone marrow transplantation comparing cefoperazone in combination with sulbactam (S), N = 66, vs. cefoperazone plus mezlocillin (CM), N = 66, as empiric antibiotic therapy for fever and neutropenia. Overall duration of neutropenia was 3-55 (median, 13) days. Forty-one patients had positive initial cultures (S = 22 and CM = 19). Twelve of these 41 patients responded to initial study antibacterial agent treatment (S = 6 and CM = 6). Twenty-nine of 41 patients were withdrawn from study because of clinical deterioration, continued fever, or persistently positive cultures (S = 16 and CM = 13). Of the 90 patients who had culture-negative fever (S = 44 and CM = 46), 44 subjects responded with or without the addition of amphotericin B (S = 21 and CM = 23). Thirty-seven of 90 patients were withdrawn from study due to continued fever or clinical deterioration (S = 17 and CM = 20). Nine patients were withdrawn as a result of rash or diarrhea (S = 6 and CM = 3). We conclude that in patients undergoing bone marrow transplantation, there was no difference in efficacy between cefoperazone/sulbactam and the combination of cefoperazone plus mezlocillin in the empiric treatment of the febrile neutropenic patient. Since the majority of initial infections were due to gram positive bacteria, consideration should be given to broadening initial empiric antibacterial agent therapy with drugs that possess potent activity against these organisms.

Clinical experience with single agent and combination regimens in the management of infection in the febrile neutropenic patient.

Choice of antibiotic therapy for the management of infection in the neutropenic patient continues to challenge the clinician. The shift toward gram-positive organisms and the continuing need to provide gram-negative coverage demands the use of an agent or agents that provide coverage for the spectrum of potential infecting organisms. Cefepime is an extended-spectrum fourth-generation cephalosporin that has good activity against gram-positive and gram-negative organisms; in addition, it resists degradation by Bush group 1 beta-lactamases. These properties make this agent a promising candidate for empiric therapy with febrile neutropenic patients. Data presented in this article are from febrile neutropenic cancer patients enrolled into two randomized, prospective, nonblinded comparative U.S. clinical trials. Patients were randomized to receive cefepime (2 g thrice daily) or a comparator regimen of either ceftazidime (2 g thrice daily) or piperacillin + gentamicin (3 g every 4 hours + 1.5 mg/kg every 8 hours). When indicated, vancomycin was added to the regimen. A total of 109 febrile episodes were treated with cefepime and 107 episodes were treated with the comparator regimens. Neutropenia (< or = 500 PMNs/mm3) persisted for > or = 10 days in >40% of episodes and severe neutropenia (< or = 100 PMNs/mm3) in >25%. More than 40% of the total number of episodes were documented bacterial infections. These characteristics did not differ among treatment groups. Duration of therapy was similar in both groups (median: cefepime, 9 days; comparators, 11 days). In >40% of episodes, patients received study therapy without addition of other antibacterials (cefepime, 46%; comparators, 41%). Vancomycin was added in almost half of all the episodes (cefepime, 45%; comparators, 53%). Patients became afebrile by the fourth day of study therapy in approximately 60% of episodes (cefepime, 58%; comparators, 60%). In approximately 75% of the episodes, patients had a satisfactory response at the end of therapy (cefepime, 74%; comparators, 76%); and following approximately 90% of episodes, patients survived for >30 days (cefepime, 90%; comparators, 92%). Eradication rates were similar for all pathogens for cefepime and comparator agents. There were similar numbers of superinfecting organisms in each treatment arm; most involved gram-positive organisms. These multiple measures of efficacy suggest that initial empiric cefepime monotherapy is comparable to the pooled experience with standard therapies and that antibacterial modifications occur with similar frequency for cefepime compared with standard empiric regimens.

Acute leukaemia following renal transplantation.

Four renal transplant patients on immunosuppressive therapy who presented with acute myeloid leukaemia are described. In two cases, azathioprine may have played an important role as a cofactor in leukaemogenesis. In a third case, the alkylating agent cyclophosphamide may have contributed. All patients were treated for leukaemia with full doses of cytotoxic chemotherapy and, in each case, a functioning renal allograft was preserved throughout the treatment despite attenuation of immunosuppressive therapy. Three patients achieved complete remission. Of the three, one is surviving at 2 years and two expired during the pancytopenic phase of their treatment with no active leukaemia present, and with intact renal function. As increasing expertise in the field of organ transplantation allows patients to survive longer, such patients' exposure to immunosuppressive and potentially leukaemogenic drugs is prolonged. The risk of secondary neoplasia has been previously documented in this population. Two of the four cases reported here suffered from polycystic kidney disease as their underlying condition. While this report suggests that the leukaemias are related to renal transplantation, we cannot rule out an association with the underlying disease which led to the transplant. This report further suggests that the leukaemia that develops in such patients may respond to standard therapy, and that such treatment does not compromise the transplanted kidney.

Pilot study of high-dose mitoxantrone and busulfan plus autologous bone transplantation in patients with advanced malignancies.

We performed a pilot trial of high-dose mitoxantrone 15 mg/m2 by i.v. infusion daily on days -6 to -4 and busulfan 1 mg/kg orally every 6 h (16 doses) on days -7 to -4 plus autologous bone marrow transplantation (BMT) in 10 patients with advanced cancer to determine the safety and feasibility of the combination. The median age of the study group was 42 years, all were women and all had progressed after prior chemotherapy (including doxorubicin in seven cases). Disease types included adenocarcinoma of the breast (n = 6) or ovary (n = 3), and non-Hodgkin's lymphoma (n = 1). The median time to an absolute neutrophil count > or = 0.5 x 10(9)/L and platelets > or = 50 x 10(9)/L were 16.5 and 28 days, respectively. There was a high degree of severe regimen-related toxicity, including severe mucositis (n = 7) and veno-occlusive disease (VOD) of the liver (n = 3). Three patients developed multisystem failure and died within 90 days of autologous BMT from complications related to VOD of the liver (n = 2) or septic shock (n = 1). We conclude that the dose and schedule of busulfan and mitoxantrone used in this study was associated with a high degree of unacceptable regimen-related toxicity.

Treatment of cancer-associated hypercalcemia. Double-blind comparison of rapid and slow intravenous infusion regimens of pamidronate disodium and saline alone.

BACKGROUND: We assessed the effects of 60-mg single doses of pamidronate disodium compared with saline alone in the treatment of cancer-associated hypercalcemia. METHODS: After pretreatment hydration, patients with corrected serum calcium concentrations of 3.0 mmol/L (12 mg/dL) or greater secondary to cancer were randomized to double-blind treatment with a single infusion of pamidronate disodium, 60 mg, over either 4 or 24 hours or continued infusions of 0.9% saline alone (n = 23 per group). Corrected serum calcium levels were measured daily for 7 days of inpatient evaluation. RESULTS: Response rates for both of the pamidronate regimens were significantly (P < .05) higher than that for saline alone. A complete response to treatment (corrected serum calcium concentration normalized) was observed for five (22%), 18 (78%), and 14 (61%) patients, respectively, who received saline alone, 4-hour infusion of pamidronate, and 24-hour infusion of pamidronate. There were no significant differences between the two pamidronate regimens. Median durations of complete response were 6, 6, and 11 days, respectively, and median times to relapse (includes complete plus partial responders and nonresponders) were 0, 7, and 7 days, respectively. Pamidronate was well tolerated as assessed by all clinical and laboratory measures, regardless of the time of infusion. CONCLUSIONS: A 4-hour infusion of pamidronate disodium, 60 mg, was as safe and effective as a 24-hour infusion, and both were superior to saline alone in lowering corrected serum calcium concentrations in patients with cancer-associated hypercalcemia.

Phase II studies of recombinant human interleukin-4 in advanced renal cancer and malignant melanoma.

Interleukin (IL-4) is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 micrograms/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 micrograms/m2, but after three of these patients developed cardiac toxicities, the dose was decreased to 600 micrograms/m2. One complete response occurred in a patient with metastatic melanoma (duration > or = 30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma.

Comparison of preparative transplantation regimens using carmustine/etoposide/cisplatin or busulfan/etoposide/cyclophosphamide in lymphoid malignancies.

Most bone marrow transplantation preparative regimens use total body irradiation as one component. Recently, however, two non-total body irradiation containing autologous bone marrow transplantation preparative regimens have been evaluated in patients with lymphoid malignancies. The first regimen consisted of carmustine, etoposide, and cisplatin; some patients also received involved-field radiotherapy to sites of prior disease. Of the 79 patients with relapsed or refractory lymphoma who participated in this study, 57 (72%) achieved a complete remission and 40 (51%) remain in complete remission. Treatment-related deaths occurred in five patients (6%). The second preparative regimen evaluated consisted of busulfan, etoposide, and cyclophosphamide and included 21 patients with Hodgkin's lymphoma, non-Hodgkin's lymphoma, or acute lymphocytic leukemia. Sixteen patients (76%) achieved complete remission and 12 (57%) remain disease free. The regimen-related mortality rate in this study was 14%. The three treatment-related deaths were all due to pulmonary toxicity. The results of these clinical trials indicate that both the carmustine/etoposide/cisplatin regimen and the busulfan/etoposide/cyclophosphamide regimen are effective in treating lymphoid malignancies. Treatment-related toxicities and deaths are significant, but not prohibitive. Accordingly, these new preparative regimens deserve further evaluation in the treatment of patients with lymphoma or leukemia.

Long-term follow-up of treatment and potential cure of adult acute lymphocytic leukemia with MOAD: a non-anthracycline containing regimen.

A total of 55 previously untreated adults with acute lymphocytic leukemia (ALL), median age 38 years (range 15-73 years), were treated with MOAD (methotrexate, vincristine, L-asparaginase, and dexamethasone). This regimen includes five phases--induction, consolidation, cytoreduction, maintenance, and central nervous system (CNS) prophylaxis with parenteral high-dose methotrexate. Of the 55 evaluable patients, 42 achieved complete remission 76%), with a median CR duration of 12+ months (range 0.5-195+ months). The median survival in remission is 22+ months (range 1-198+ months), with 33% of remitters continuing in long-term remissions (> 5 years). Two out of four patients who developed CNS leukemia did so without marrow relapse, were successfully treated for that complication, and continue in total complete remission at 8+ and 16+ years. Another patient with extramedullary relapse (breast) was treated with radiation to that site and remains in total CR at 16+ years. Expected toxicities included myelosuppression during the induction phase of treatment, with 65% of patients requiring intravenous antibiotics. Mucositis was the next most frequent toxicity and required dose-reduction in seven patients. Minimal toxicity was seen during the post-remission phases of treatment. L-Asparaginase toxicity was more prominent during intravenous administration (24 patients) than when the intramuscular route of administration (30 patients) was used. The remission rate and long-term survivorship achieved with this regimen, without the use of an anthracycline, is comparable to that of other regimens for adult ALL. MOAD was well-tolerated by young and old adults with ALL. Aseptic necrosis of bone, successfully treated in each instance, occurred in four long-term disease-free survivors. The effect of this complication and its treatment on quality of life has been negligible.

Nosocomial infections in neutropenic cancer patients.

OBJECTIVE: Identification of overall and site-specific rates of nosocomial infection in neutropenic patients with cancer and associated pathogens. DESIGN: Cumulative continuous prospective surveillance over a 42-month period. Criteria and definitions of infection in neutropenic patients (absolute neutrophil counts < 1,000/mm3) were developed, and surveillance was carried out by a certified infection control nurse and a senior oncology research fellow. SETTING: A cancer research center with two designated oncology nursing units. PATIENTS: Neutropenic patients with hematological and solid malignancies undergoing high-dose chemotherapy with and without autologous bone marrow transplantation. All patients admitted to both of the units during the study period were surveyed. Those who developed neutropenia are included in this report. RESULTS: A total of 444 nosocomial infections were identified in 920 neutropenic patients during 9,582 days of neutropenia for an overall rate of 48.3 per 100 neutropenic patients, or 46.3 per 1,000 days at risk. The rate of bloodstream infection per 100 neutropenic patients was 13.5 (gram-positive, 9.2; gram-negative, 4.8; and Candida 1.2). Other site-specific rates were: urinary tract, 5.7; respiratory tract, 5.5; thrush, 6.6; skin, 3.4; and gastrointestinal tract, 3.4. Among 392 pathogens identified, there were 137 (35%) gram-positive cocci, 105 (27%) gram-negative rods, 70 (18%) Candida, 37 (9%) gram-positive rods, 22 (6%) viruses, and 15 (4%) Aspergillus. CONCLUSIONS: The rate of both overall and site-specific nosocomial infections in neutropenic patients is high. Neutropenia is a significant intrinsic risk factor that should be addressed in surveillance programs. Infection control and infectious diseases practitioners may need to modify techniques for surveillance, control, and management of infection in this population.

Survival after phase II treatment of advanced renal cell carcinoma with taxol or high-dose interleukin-2.

From 1986 to 1989, 71 patients with advanced renal cell carcinoma were treated at one institution with either the Phase II agent, taxol, or one of several high dose interleukin-2 (IL-2) protocols. As no responses to taxol were seen, that group may represent the natural history of renal cell carcinoma in a Phase II population. The results of treatment with IL-2 were examined against this background. Concurrently, 17 patients received taxol and 14 patients IL-2. An additional 40 patients subsequently received IL-2. Five taxol patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 were excluded from the comparison as similar patients were ineligible for the IL-2 studies. There were more patients in the IL-2 groups with non-liver/lung metastases and ECOG PS 0 than in the taxol group. Six (43%) of concurrent IL-2 patients responded [complete response (CR) = 14%; partial response (PR) = 29%]. The response rate for all IL-2-treated patients was 22% (CR +/- 7%, PR +/- 15%). The response rate to IL-2 was higher in cases with ECOG PS 0, time to treatment < 12 months, and no prior chemotherapy. The median time to progression for the concurrent IL-2 group was 4.5 months (4.0 months for all IL-2 patients) and 2.5 months for taxol patients. Median survival for concurrent IL-2 patients was 12.5 months (12 months for all IL-2 patients) and 10 months for taxol patients. Durable remissions resulted in a 21% overall survival at 40 months for all IL-2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma.

PURPOSE: To determine better the activity of high-dose interleukin-2 (IL-2) either alone or in combination with interferon alfa-2b (IFN; Schering-Plough, Kenilworth, NJ) in patients with metastatic renal cell carcinoma, the IL-2 Working Group initiated a randomized phase II trial. PATIENTS AND METHODS: Patients were randomly assigned to receive treatment with either IL-2 (Chiron Corp, Emeryville, CA) 1.33 mg/m2 (approximately 600,000 IU/kg) alone or IL-2 0.8 mg/m2 and IFN 3 x 10(6) U/m2 administered by bolus intravenous injection every 8 hours, days 1 to 5 and 15 to 19 (maximum, 28 doses). All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and normal organ function. After 28 patients were entered onto each arm, the IL-2/IFN arm was closed because of a failure to meet predetermined efficacy criteria. An additional 43 patients (total, 71) were assigned to receive IL-2 alone. RESULTS: Toxicities were similar for both study arms. Hypotension requiring pressors was the most frequent dose-limiting toxicity. Only 11 of 99 patients experienced severe toxicity; there were no irreversible side effects or treatment-related deaths. Responses were seen in three of 28 patients (11%) on IL-2/IFN (three partial responses [PRs] lasting 14, 7, and 7 months) and 12 of 71 patients (17%) on IL-2 alone (four complete responses [CRs] and eight PRs). Six of the partial responders on IL-2 and two on IL-2/IFN experienced greater than 90% reduction in tumor mass. Ten of the 12 responders to IL-2 have ongoing responses of 12+ to 26+ months in duration. CONCLUSION: We conclude that both IL-2 and IL-2/IFN therapy have activity in metastatic renal cell carcinoma. In particular, therapy with high-dose IL-2 alone produces meaningful and durable responses with manageable and reversible toxicity. This study supports the contention that high-dose IL-2 represents the treatment of choice in selected patients with advanced renal cell carcinoma.

Clostridium cadaveris bacteremia in the immunocompromised host.

Clostridium cadaveris, usually considered a non-pathogen, was isolated from blood cultures of two febrile patients with cancer. The bacteremias appeared to have originated from the abdomen. This organism has not been previously reported as the etiological agent in this setting.

High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.

PURPOSE: We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. PATIENTS AND METHODS: Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites. RESULTS: Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion. CONCLUSIONS: This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).

Lymphoid lineage-associated features in acute myeloid leukaemia: phenotypic and genotypic correlations.

This study is intended to establish biological correlation between the expression of lymphoid associated features in acute myeloid leukaemia (AML). In 62 AML patients, predominantly enrolled on Eastern Cooperative Oncology Group (ECOG) treatment protocols, in whom immunoglobulin (Ig) as well as T-cell receptor beta chain (TCR-beta) gene rearrangement analyses had been performed, morphology, cytochemistry, antigen profile and karyotype were reviewed retrospectively. Nuclear reactivity with anti-TdT antibody was demonstrated in 34 patients (55%) and confirmed by ribonuclease protection assay in all patients tested. Five TdT-protein negative patients were TdT-transcript positive. Lymphoid antigens (lyA) were detected in 24 of 51 cases tested (47%) with B-cell antigens (CD19, CD10) being restricted to TdT+ AML (P = 0.03). Only two patients had Ig heavy, none had Ig light chain or TCR-beta gene rearrangements. Although both patients with rearranged Ig loci were TdT+, either by protein or RNA analysis, the low incidence of such rearrangement within the TdT+ AML group (6%) argues against a significant association between the presence of TdT and crosslineage Ig gene rearrangements in AML. While FAB-diagnoses did not differ between TdT+ and TdT- or lyA+ and lyA- AML, particular immunophenotypic features correlated with TdT positively, e.g. the presence of early antigens, CD34 and HLA-DR, and the absence of the more mature myelo-monocytic antigens, CDw65 and CD14. Certain cytogenetic abnormalities were associated with TdT+ AML such as inv(16) (p13q22) or t(16;16) (p12;q22) (five patients; P = 0.03) and t(8;21) (q22;q22) (three patients). A greater number of TdT- than TdT+ AML patients had only normal karyotypes (P = 0.06). Neither immunophenotypic nor karyotypic correlations could be established for lyA+ AML.