Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study.

PURPOSE: Bacillus Calmette-Guerin (BCG) immunotherapy has been widely accepted as the optimal treatment for carcinoma in situ and high grade superficial transitional cell carcinoma. However, controversy remains regarding the role of maintenance therapy, and its long-term effect on recurrence and progression. MATERIALS AND METHODS: All patients in the study had transitional cell carcinoma of the bladder with carcinoma in situ or an increased risk of recurrence. The criteria for increased risk were 2 or more episodes of tumor within the most recent year, or 3 or more tumors within 6 months. At least 1 week following biopsy of carcinoma in situ and resection of any stage Ta or T1 transitional cell tumors 660 patients were started on a 6-week induction course of intravesical and percutaneous Connaught BCG. Three months following initiation of BCG induction therapy 550 consenting patients were stratified by purified protein derivative skin test and the presence of carcinoma in situ, and then randomized by central computer to receive BCG maintenance therapy (maintenance arm) or no BCG maintenance therapy (no maintenance arm). Maintenance therapy consisted of intravesical and percutaneous BCG each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months from initiation of induction therapy. The 384 eligible patients who were disease-free at randomization constitute the primary intent to treat analytic group because they could be followed for disease recurrence. All patients were followed for adverse effects of treatment, recurrence, disease worsening and survival. RESULTS: No toxicities above grade 3 were noted in the 243 maintenance arm patients. The policy of withholding maintenance BCG from patients with increased side effects may have diminished the opportunity to observe severe toxicity. Estimated median recurrence-free survival was 35.7 months (95% confidence interval 25.1 to 56.8) in the no maintenance and 76.8 months (64.3 to 93.2) in the maintenance arm (log rank p<0.0001). Estimated median time for worsening-free survival, defined as no evidence of progression including pathological stage T2 disease or greater, or the use of cystectomy, systemic chemotherapy or radiation therapy, was 111.5 months in the no maintenance and not estimable in the maintenance arm (log rank p = 0.04). Overall 5-year survival was 78% in the no maintenance compared to 83% in the maintenance arm. CONCLUSIONS: Compared to standard induction therapy maintenance BCG immunotherapy was beneficial in patients with carcinoma in situ and select patients with Ta, T1 bladder cancer. Median recurrence-free survival time was twice as long in the 3-week maintenance arm compared to the no maintenance arm, and patients had significantly longer worsening-free survival.

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma.

BACKGROUND: Rituximab is a chimeric monoclonal antibody directed against the B-cell CD20 antigen which has been utilized for therapy of B-cell non-Hodgkin's lymphoma (NHL). A previous clinical trial demonstrated that treatment with four weekly doses of 375 mg/m2 of Rituximab in patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma was well tolerated and had significant clinical activity. PATIENTS AND METHODS: To assess the safety and efficacy of Rituximab treatment, an open-label, single-arm, multi-center, phase II study of eight consecutive weekly infusions of 375 mg/m2 Rituximab in patients with low-grade or follicular B-cell NHL who had relapsed or had failed primary therapy was conducted. Thirty-seven patients with a median age of 55 years were treated. RESULTS: Grade 1 or 2 adverse events were the majority of reported toxicities and occurred most frequently with the first infusion, decreasing with subsequent infusions. No patients developed a host antibody response (HACA) to Rituximab. The mean serum immunoglobulin levels for IgG, IgA, and IgM stayed within the normal range throughout the study. The majority of patients who were bcl-2 positive at baseline in peripheral blood became bcl-2 negative during treatment and remained negative at the time of B-cell recovery. In the 37 intent-to-treat patients, 5 (14%) had a complete response and 16 (43%) had a partial response for an overall response rate of 57%. Of 35 evaluable patients, 21 (60%) responded to treatment (14% CR and 46% PR). In responders, the median time to progression (TTP) and the median response duration have not been reached after 19.4+ months and 13.4+ months, respectively. CONCLUSIONS: The safety profile and efficacy achieved in this pilot study of extended treatment with Rituximab compares favorably with those seen with four weekly doses. Further studies are warranted to investigate whether this or other extended Rituximab schedules will result in increased efficacy in all or in certain subgroups of patients with low-grade or follicular NHL.

Paclitaxel formulation as a cause of ethanol intoxication.

OBJECTIVE: To report a case of ethyl alcohol intoxication associated with paclitaxel administration. CASE SUMMARY: A patient who received a 3-hour paclitaxel infusion for metastatic breast carcinoma and developed symptoms of acute alcohol intoxication. A blood ethanol concentration drawn at the end of the paclitaxel infusion was 97.8 mg/dL (0.098%). DISCUSSION: The amount of alcohol contained in paclitaxel is discussed. A review of the literature revealed one patient series where the highest blood alcohol concentration was one-third that seen in our patient. CONCLUSIONS: Clinicians should recognize the potential for alcohol intoxication with paclitaxel administration. This is especially pertinent when higher doses are given over a short period of time.

Oral ondansetron 8 mg twice daily is as effective as 8 mg three times daily in the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy. S3A-376 Study Group.

The efficacy and safety of ondansetron 8 mg BID compared with 8 mg TID for 3 days in the prevention of nausea and vomiting in 402 patients on cyclophosphamide (> or = 500 mg/m2)-based chemotherapy were evaluated in a multicenter, randomized, double-blind, stratified study. The percentage of patients with no emetic episodes over the 3-day study period was 61% in the ondansetron BID group compared with 58% in the ondansetron TID group. Among patients with at least one emetic episode, the mean time to emesis was 14 hr and 17 min in the ondansetron BID group compared with 12 hr and 48 min in the ondansetron TID group. Patients' daily appetite ratings and nausea scores were not significantly different between groups. Clinical laboratory and adverse event profiles were similar between groups. This study is the first large-scale, double-blind trial to demonstrate that ondansetron 8 mg BID for 3 days, a dosing regimen that may enhance patient convenience and compliance, is as effective as ondansetron 8 mg TID for 3 days in the prevention of nausea and vomiting associated with cyclophosphamide-based chemotherapy.

Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo.

PURPOSE: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.

The pattern of emesis following high-dose cyclophosphamide and the anti-emetic efficacy of ondansetron.

Two randomized, double-blind placebo-controlled ondansetron dose ranging studies in patients receiving high-dose cyclophosphamide (with or without doxorubicin) were completed in the US. These studies enable the pattern of emesis and nausea for 3 days following high-dose cyclophosphamide to be described and give some insight into the mechanisms of emesis which may be operating. Nausea and vomiting induced by cyclophosphamide-based chemotherapy has a long latency of onset (8-13 h) and continues for at least 3 days. These findings are of particular importance as many of these patients receive chemotherapy as outpatients and emphasize the need for appropriate anti-emetic prophylaxis for patients at home. Ondansetron was extremely effective over this time in the control of emesis and nausea. These results suggest that high-dose cyclophosphamide-induced emesis over days 1-3 is largely mediated via 5-hydroxytryptamine (5-HT) and 5-HT3 receptors.

A randomized, double-blind comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin-induced emesis.

PURPOSE: This study compares the efficacy and safety of ondansetron alone with that of ondansetron plus dexamethasone in the prevention of emesis induced by high-dose cisplatin (> or = 100 mg/m2). PATIENTS AND METHODS: This multicenter study used a randomized, double-blind, parallel-group design. Chemotherapy-naive patients were randomized to receive intravenous (IV) ondansetron (Zofran, Cerenex Pharmaceuticals, Research Triangle Park, NC) 0.15 mg/kg for three doses every 4 hours beginning 30 minutes before cisplatin administration either alone or in combination with dexamethasone 20 mg administered 45 minutes before cisplatin. Cisplatin (> or = 100 mg/m2) was administered as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes (EEs), adverse events, and laboratory safety parameters for 24 hours after cisplatin administration. RESULTS: A total of 275 patients were enrolled. Of these, 245 were assessable for efficacy. Patients who received ondansetron plus dexamethasone had a higher complete antiemetic response rate (61% v 46%, P = .02) and less nausea (posttreatment visual analog scale mean 18.2 v 32.8, P < .001) than did those who received ondansetron alone. The time to the first EE was longer for patients in the group that received ondansetron plus dexamethasone (P = .005). Headache (12%), diarrhea (2%), and abdominal colic (1%) were the most common antiemetic-related adverse events reported. The incidence of adverse events was similar between the treatment groups. CONCLUSION: IV ondansetron in combination with dexamethasone is safe and more effective than ondansetron alone in the prevention of emesis induced by high-dose cisplatin.

Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. The Ondansetron Study Group.

OBJECTIVE: To evaluate the efficacy and safety of oral ondansetron (Zofran) as an antiemetic in patients receiving cyclophosphamide-based chemotherapy. DESIGN: A multicenter, randomized, double-blind, stratified, placebo-controlled trial conducted between March 1989 and January 1990. SETTING: Twenty-seven oncology centers including university hospitals, community cancer centers, and private medical oncology practices. PATIENTS: A total of 349 chemotherapy-naive patients having their first cycle of cyclophosphamide (> or = 450 mg/m2)-based chemotherapy. Patients also received methotrexate (> or = 30 mg/m2) or doxorubicin (> or = 35 mg/m2). All patients were evaluated for safety and 318 (91%) were evaluated for efficacy. INTERVENTIONS: Patients were randomly assigned to one of four treatment groups: placebo, 1 mg, 4 mg, or 8 mg of ondansetron. Assigned study medication was taken three times per day for 3 consecutive days. MEASUREMENTS: Time and number of emetic episodes as well as degree of nausea were recorded by patients for each of the 3 study days. RESULTS: Compared with placebo, all three doses of ondansetron were superior (P < 0.001) in preventing vomiting and controlling nausea. A complete response (no emetic episodes) was observed in 19%, 57%, 65%, and 66% of patients in the placebo, 1-mg, 4-mg, and 8-mg ondansetron groups, respectively. For patients who received higher-dose cyclophosphamide and doxorubicin, a dose-related trend in antiemetic efficacy of ondansetron was observed. Mild headache and constipation were the most frequently reported adverse events. No extrapyramidal reactions were observed. CONCLUSION: Oral ondansetron is a safe and effective antiemetic that is more efficacious than placebo for patients receiving cyclophosphamide-based chemotherapy.

Efficacy of ondansetron tablets in the management of chemotherapy-induced emesis: review of clinical trials.

The selective 5-hydroxytryptamine3 antagonist ondansetron has been shown to be effective in preventing nausea and vomiting associated with highly emetogenic cisplatin chemotherapy. Two multicenter, placebo-controlled, dose-comparison studies (S3A-361 and S3A-362) were undertaken to investigate the efficacy and safety of oral ondansetron in patients receiving non-cisplatin, cyclophosphamide-based regimens in the outpatient setting. Chemotherapy-naive patients undergoing their first cycle of cyclophosphamide-based (> or = 500 mg/m2) chemotherapy were randomized to receive placebo or ondansetron, 1, 4, or 8 mg, three times per day for 3 days. In addition to cyclophosphamide, all patients received doxorubicin, methotrexate, or another low-to-moderately emetogenic agent. In study S3A-361, 318 of 349 patients were evaluable for efficacy; 297 of 324 patients in study S3A-362 were evaluable for efficacy. All patients in both studies were evaluable for safety. All ondansetron groups were superior to placebo groups in both studies for all measured efficacy parameters. In the two studies combined, 14%, 47%, 65%, and 66% of patients in the placebo, 1-, 4-, and 8-mg ondansetron groups, respectively, experienced no emetic episodes. The rate of therapeutic failure was statistically lower in the ondansetron groups in both studies compared with the placebo groups. In addition, therapeutic failure decreased in a dose-dependent manner. Severity of nausea, food intake, time to first emetic episode, and need for rescue antiemetics were also improved for the ondansetron groups. When the patients were stratified for doxorubicin-containing regimens, those patients receiving doxorubicin had a lower response rate with placebo and ondansetron than those on non-doxorubicin regimens. However, a dose-related improvement in efficacy was still observed with ondansetron in this subset of patients. In patients receiving the more emetogenic high-dose cyclophosphamide (> or = 600 mg/m2) regimens, a dose-related improvement in efficacy also was observed. In conclusion, oral ondansetron was found to be an effective and safe antiemetic for patients receiving cyclophosphamide-based chemotherapy in the outpatient setting. The 8-mg dose was optimal, particularly in patients receiving doxorubicin-containing or high-dose cyclophosphamide regimens.

Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting.

PURPOSE: This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis. PATIENTS AND METHODS: This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy-naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.15 mg/kg times three doses, every 4 hours or a single 8-mg or 32-mg dose followed by two saline doses that began 30 minutes before cisplatin administration. Cisplatin (high-dose > or = 100 mg/m2 or medium-dose 50 to 70 mg/m2) was given as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 hours after cisplatin administration. RESULTS: A total of 699 patients (359 high-dose, 340 medium-dose) were enrolled. Of these, 618 were assessable for efficacy (15 ineligible, 66 protocol deviations). The 32-mg dose was superior to the 8-mg single dose with regard to total number of emetic episodes (high-dose, P = .015; medium-dose, P < .001), complete response (no emetic episodes: high-dose, 48% v 35%; P = .048; medium-dose, 73% v 50%; P = .001) and failure rate (> 5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005). The 32-mg single dose was also superior to the 0.15 mg/kg times three dose regimen with regard to total number of emetic episodes (medium-dose, P = .033) and failure rate (high-dose, 20% v 36%; P = .009; medium-dose, 9% v 22%; P = .011). Ondansetron was well tolerated. The most common adverse event was headache. An approximate 10-fold increase in the incidence of clinically significant transaminase elevations was observed in the high-dose versus medium-dose cisplatin strata (aspartate aminotransferase [AST], 6.5% v 0.7%; serum alanine aminotransferase [ALT], 5.0% v 0.3%). CONCLUSION: A 32-mg single dose of ondansetron is more effective than a single 8-mg dose and is at least as effective as the standard regimen of 0.15 mg/kg times three doses in the prevention of cisplatin-induced acute emesis.

Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study.

The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer.

The genome of bovine herpesvirus 1 (BHV-1) strains exhibiting a neuropathogenic potential compared to known BHV-1 strains by restriction site mapping and cross-hybridization.

Bovine herpesvirus 1 (BHV-1) strains can be differentiated by their DNA and polypeptide patterns, and by antigenic properties as demonstrated by monoclonal antibodies. We classified the BHV-1 strains according to these data as BHV-1.1, BHV-1.2 (a/b) and BHV-1.3 (a/b). BHV-1.1 and BHV-1.2 correspond to the well known 'common' BHV-1 strains, whereas BHV-1.3 has only recently been recognized and exhibits a neuropathogenic potential. In the present paper we describe the structural genome characteristics of BHV-1.3 compared to those of the other BHV-1 strains, examined by means of restriction site mapping, electron microscopy and cross-hybridization. Our results also confirm and complete data concerning BHV-1.1 and BHV-1.2 published by other authors. The following main conclusions can be drawn from our investigations: BHV-1.1 and BHV-1.2 differences are restricted to distinct genomic regions, characterized by loss or gain of restriction sites. BHV-1.3, however, differs from the other BHV-1 strains in restriction site alterations throughout the whole genome. Electron microscopy showed the typical BHV-1 DNA structure for BHV-1.3. Genetic homology between BHV-1.1 and BHV-1.2, reported to be about 95%, was confirmed by cross-hybridization, and a similar high base sequence homology for BHV-1.3 could be shown.

Granulocytic sarcoma treated as an acute leukemia. Report of a case.

A young man presented with intestinal obstruction. Laparotomy revealed a large mass encircling the cecum and terminal ileum which histologically proved to be a granulocytic sarcoma. No evidence of leukemia was present in peripheral blood or bone marrow. Initial therapy consisted of abdominal irradiation. Two months following completion of irradiation, widespread systemic involvement without leukemia was evident. Systemic chemotherapy with doxorubicin, cytosine arabinoside, vincristine, and prednisone was initiated. Chemotherapy was continued for 18 months. The patient has remained without evidence of disease for 49 months following discontinuation of treatment, and 67 months after initial diagnosis. Systemic therapy for granulocytic sarcoma presenting without evidence of leukemia is reviewed.

Treatment of metastatic colorectal carcinoma with 5-FU, mitomycin, vincristine, and methotrexate.

Fifty-three patients with advanced metastatic colorectal carcinoma were treated every 4-5 weeks with a chemotherapeutic regimen consisting of 5-FU (300 mg/m2 iv on Days 1-5), mitomycin (10 mg/m2 iv on Day 1 only [repeated every other course]), vincristine (0.75 mg/m2 on Days 1 and 5), and methotrexate (8.0 mg/m2 iv on Days 1 and 5). The overall response rate was 43.4%, with three patients (5.7%) achieving complete response (mean duration, 13.3 months) and 20 patients (37.7%) achieving partial response (mean duration, 6.3 months). Stable disease was not considered to be a response category in this report. The mean overall response duration was 7.8 months. The observed mean survival duration in responders was 15.2 months and in nonresponders was 8.9 months (P less than or equal to 0.01). Hematologic and subjective toxic effects are discussed.

Local or regionally recurrent carcinoma of the breast: results of therapy in 121 patients.

Local or regional recurrence after primary surgical management for carcinoma of the breast was retrospectively evaluated by presenting stage and management in 121 patients. None had evidence of systemic disease. Management consisted of surgical removal only in 11 patients, removal followed by irradiation in 25, biopsy only followed by irradiation in 43, hormonal therapy after biopsy in 30, and chemotherapy after biopsy in 12. Mean and median follow-up for all patients was 46.9 and 31.5 months, respectively. Patients experiencing a recurrence within 24 months of primary surgical management experienced the worst overall and disease-free survival. The group of 42 patients with residual disease who received systemic therapy after biopsy had improved disease-free and overall survival at 5 years in comparison to the group of 43 patients who received local therapy after biopsy (p less than or equal to 0.05). Radiation therapy produced more frequent and durable control of local disease than did systemic therapy. Patients who had a complete response to applied therapy had significant improvement in overall survival.

Hodgkin's disease in a community oncology center: ten years' experience.

A total of 77 cases of Hodgkin's disease have been evaluated and the patients treated at our institution during the past ten years. Advances in diagnostic technology and therapy have improved the outcome of the disease and overall survival. Therapy during this period has not been standardized. Radiation therapy was the primary initial treatment for stages I, II and III, with combined-modality therapy or chemotherapy alone used for more advanced stages. Five-year disease-free and overall survival for stage IA is 81 percent and 95 percent, respectively; 74 percent and 78 percent for stage IIA; 70 percent in both instances for stage IIB; 54 percent and 100 percent for stage IIIA; 75 percent and 100 percent for stage IIIB, and 57 percent and 69 percent for stage IV. Of 13 patients initially treated with chemotherapy, 77 percent have had a complete response. Of the 16 patients (88 percent) having a relapse, 14 have been salvaged with a variety of therapeutic approaches. Overall, five-year survival for 77 patients is 86 percent, with 70 percent having no relapse.

Fatal graft-versus-host disease in a patient with lymphoblastic leukemia following normal granulocyte transfusion.

A woman with lymphoblastic lymphoma was treated with combination chemotherapy. She subsequently became febrile while granulocytopenic and was given unirradiated granulocyte transfusions from normal, unrelated donors. She recovered, but 12 days later noted the onset of progressive skin rash, hepatic dysfunction, diarrhea and pancytopenia and, 22 days after her last granulocyte transfusion, died of gram negative septicemia. Histologic examination of multiple tissues including the skin, liver, and intestinal tract showed changes characteristic of acute graft-versus-hose disease (GVHD). Y-chromatin analysis of the patient's peripheral blood just before death indicated the presence of male cells. HLA typing of lymphocytes and skin fibroblasts from the patient and lymphocytes from the family and granulocyte donors was also consistent with engraftment of cells from one of the male granulocyte donors. This donor most likely was homozygous for one of the patient's halotypes, perhaps facilitating engraftment of his cells and subsequent development of transfusion-induced acute GVHD. Until more precise guidelines can be established, we recommend that all cellular blood products given to patients receiving intensive chemotherapy be irradiated with 1500 rad.

Premature chromosome condensation in human leukemia.

Premature chromosome condensation (PCC) has previously been observed in tissue culture and is believed to arise from asynchronous mitotic activity in multinucleated cells in which the affected nucleus is in interphase and at least one nucleus is in metaphase. Such cells have been noted following fusion induced by virus infection, spontaneously, and after treatment with cytochalasin B. The phenomenon has also been observed in malignant pleural effusions, but has not previously been described as a feature of hematologic disease. In this study, we report the observations of PCC in seven patients. Six of these patients had either acute myeloblastic leukemia or acute myelomonoblastic leukemia in association with the features of erythroleukemia, i.e., leukoerythroblastic reaction in the blood, and erythroid multinuclearity, "megaloblastoid" changes, and PAS-positive staining of erythroid precursor cells in the bone marrow. In all patients, erythroid multinuclearity has been noted. However, not all patients with erythroleukemia exhibit PCC. In this series, three additional patients have had similar bone marrow morphologic changes without PCC. The finding of PCC in erythroleukemia may have important implications as to etiology of this disorder.