Prospective study of one- vs two-unit umbilical cord blood transplantation following reduced intensity conditioning in adults with hematological malignancies.

As the threshold nucleated cell dose for one-unit umbilical cord blood (UCB) in adults has not to date been firmly established, we prospectively compared one- vs two-unit UCB transplantation after reduced intensity conditioning (RIC) in adult patients with hematological malignancies. Study design specified one-UCB unit if the cryopreserved total nucleated cell (TNC) dose was 2.5 × 10(7)/kg recipient weight, otherwise two units matched at minima of 4/6 HLA loci to the patient and 3/6 to each other were infused. A total of 27 patients received one unit; 23 patients received two units. Median time to ANC >500/µL was 24 days (95% confidence interval 22-28 days), 25 days for one unit and 23 days for two units (P=0.99). At day 100, ANC >500/µL was 88.4 and 91.3% in the one- and two-unit groups (P=0.99), respectively. Three-year EFS was 28.6% and 39.1% in the one- and two-unit groups (P=0.71), respectively. Infusion of two units was associated with a significantly lower relapse risk, 30.4% vs 59.3% (P=0.045). Infused cell doses (TNC, CD3(+), CD34(+) and CD56(+)CD3(neg)) did not impact on engraftment, OS or EFS. Taken together, one-unit UCB transplantation with a threshold cell dose 2.5 × 10(7)/kg recipient weight after RIC is a viable option for adults, although infusion of two units confers a lower relapse incidence.

Time-dependent effect of non-Hodgkin's lymphoma grade on disease-free survival of relapsed/refractory patients treated with high-dose chemotherapy plus autotransplantation.

Evaluation of time to event outcomes usually is examined by the Kaplan-Meier method and Cox proportional hazards models. We developed a modified statistical model based on histologic grade and other variables to describe the time-dependent outcome for autologous stem cell transplant (autotransplant) performed for non-Hodgkin's lymphoma (NHL) based on histologic grade and other variables. One hundred and fourteen relapsed or refractory NHL patients were treated using BCNU 600 mg/m2, etoposide 2400 mg/m2, and cisplatin 200 mg/m2 IV followed by autotransplant. Median age was 53.5 (range: 25-70) years, 78 patients had aggressive NHL and 36 indolent NHL. Seventy-five patients received involved-field radiotherapy just prior to transplant. At a median follow-up of 33 (range: 3 to 118) months, the estimated 5-year Kaplan-Meier probabilities of overall survival and disease-free survival were 61% and 51%, respectively. Cox proportional hazards model analysis showed that proportionality did not hold for lymphoma grade, indicating that the relationship between the grade and disease-free survival differed over time. By piece-wise Cox model, the relative risk for experiencing relapse or death after 1 year in patients with indolent compared with patients with aggressive NHL was 2.81 (p=0.019) with 95% confidence interval (1.19, 6.65). The time-dependent effect of lymphoma grade on disease-free survival suggests the need for early (within first year) incorporation of novel therapeutic approaches in management of patients with indolent NHL undergoing autotransplant.

Pre-mobilization therapy blood CD34+ cell count predicts the likelihood of successful hematopoietic stem cell mobilization.

We examined pre-mobilization blood CD34+ cell count to predict ability to mobilize adequate peripheral blood progenitor cells (PBPC) in 106 cancer patients and 36 allogeneic donors. Mean pre-mobilization therapy blood CD34+ cell count was 3.1 cells x 10(6)/l (s.d. = 3.9, r = 0.3-37) and mean CD34+ cells collected were 5.3 x 10(6) cells/kg/leukapheresis procedure (s.d. = 7.0, r = 0.03-53). Yields correlated with pre-mobilization CD34+ cells x 10(6)/l (r = 0.37, P-value < 0.0001); correlation was stronger in allogeneic donors (r = 0.56, P-value = 0.0004) and males (r = 0.46, P-value < 0.0001). Based on classification and regression tree multivariate analysis, the predictive value of pre-mobilization blood CD34+ cell count was confounded by other variables, including age, gender, mobilization regimen and malignancy type. We generated an algorithm to predict a minimum PBPC yield of 1 x 10(6) CD34+ cells/kg/leukapheresis procedure after mobilization. A threshold pre-mobilization blood CD34+ cell count of 2.65 cells x 10(6)/l was the most important decision point in predicting successful mobilization. Only 2% of subjects with pre-mobilization blood CD34+ cell counts > 2.65 cells x 10(6)/l did not achieve the minimum per apheresis, whereas 24% with pre-mobilization values below threshold had inadequate mobilization. Prospectively identifying individuals at risk for mobilization failure would allow for improved treatment planning, resource utilization and time saving.

Effect of induction chemotherapy and tandem cycles of high-dose chemotherapy on outcomes in autologous stem cell transplant for metastatic breast cancer.

We assessed the effect standard-dose induction chemotherapy and tandem cycles of high-dose chemotherapy (HDC) have on outcomes in metastatic breast cancer. One hundred and one women with metastatic breast cancer were enrolled in two non-randomized phase II studies. The first group of 64 patients (induction group) received four cycles of docetaxel 75 mg/m2 and doxorubicin 50 mg/m2. The next 37 patients did not receive induction (no induction group). Both groups received two (tandem) cycles of HDC. Blood-derived stem cells were collected after the first HDC cycle, processed using CD34+ cell selection and then reinfused after the second HDC cycle. Outcomes were compared between the two groups and also to patients participating in the Philadelphia (inter-group) randomized metastatic breast cancer transplant trial (PBT-01). Intent-to-treat analysis revealed no significant differences in complete response rates (37.5% vs 27%; P = 0.20), overall response (75% vs 71%), median progression free survival (PFS) (11.9 vs 8 months; P = 0.24) and overall survival (OS) (>36 vs 25 months; P = 0.16), in the induction vs no induction groups, respectively. Adjusting for differences in known baseline characteristics, induction group patients were found to have significantly longer PFS (P = 0.002), OS (P = 0.01) and more frequent conversion from a partial to complete response (58% vs < or = 13%, P < or = 0.0002) when compared with PBT-01 patients. Induction chemotherapy administered prior to tandem cycles of HDC does not appear to adversely affect outcomes in metastatic breast cancer patients. Outcomes in our induction group also compare favorably with those observed in PBT-01 and warrant further clinical investigation.

Treatment of primary resistant or relapsed multiple myeloma with high-dose chemoradiotherapy, hematopoietic stem cell rescue, and granulocyte-macrophage colony-stimulating factor.

In this prospective, multicenter, phase 2 study, multiple myeloma (MM) patients with primary resistant disease or recurrent chemosensitive disease, in chemoresistant relapse, or in second or subsequent remission were treated with high-dose chemoradiotherapy followed by autologous peripheral blood stem cell (PBSC) rescue. PBSCs were collected using granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 microg/kg per day subcutaneously for 3 days. Patients underwent high-dose chemoradiotherapy consisting of melphalan (140 mg/m2 x 1 day), cyclophosphamide (60 mg/kg per day x 2 days), methylprednisolone (2 g/d x 7 days), and total body radiation (150 cGy bid x 3 days) followed by peripheral blood stem cell reinfusion (> or = 1.2 x 10(9) mononucleated cells per kg) and GM-CSF support (5 microg/kg per day) and were evaluated for response, survival, and toxicity. Thirty-six patients, median age 53.4 years, completed the study. The mean pretransplantation cumulative melphalan dose was 464 +/- 72 mg. Excluding the 3 patients (8.3%) who failed to engraft, the median times to engraftment and platelet recovery were 10 days (range, 8-39 days) and 17 days (range, 7-67 days), respectively. Four patients (11.1%) died of complications related to the regimen (main causes of death, sepsis and acute respiratory distress syndrome) within the first 100 days. Twenty-two patients (61.1%) achieved complete response (CR), 8 (22.2%) partial response, and 2 (5.5%) no response. Two patients developed myelodysplastic syndrome after achieving CR. For all 36 patients, the probability of overall survival at 5 years was 27.3%. Median survival was 31 months (range, 0.3-81 months) in all patients and 42 months (range, 3.4-81 months) in those with CR. The probabilities of overall and disease-free survival at 5 years for the 22 patients who achieved CR were 43.6% and 15.7%, respectively. This high-dose chemotherapy regimen coupled with PBSC rescue is associated with a high CR rate and is capable of inducing long-term survival in a subset of heavily pretreated patients with primary resistant or recurrent MM.

Randomized cross-over trial of progenitor-cell mobilization: high-dose cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) versus granulocyte-macrophage colony-stimulating factor plus G-CSF.

PURPOSE: Patient response to hematopoietic progenitor-cell mobilizing regimens seems to vary considerably, making comparison between regimens difficult. To eliminate this inter-patient variability, we designed a cross-over trial and prospectively compared the number of progenitors mobilized into blood after granulocyte-macrophage colony-stimulating factor (GM-CSF) days 1 to 12 plus granulocyte colony-stimulating factor (G-CSF) days 7 to 12 (regimen G) with the number of progenitors after cyclophosphamide plus G-CSF days 3 to 14 (regimen C) in the same patient. PATIENTS AND METHODS: Twenty-nine patients were randomized to receive either regimen G or C first (G1 and C1, respectively) and underwent two leukaphereses. After a washout period, patients were then crossed over to the alternate regimen (C2 and G2, respectively) and underwent two additional leukaphereses. The hematopoietic progenitor-cell content of each collection was determined. In addition, toxicity and charges were tracked. RESULTS: Regimen C (n = 50) resulted in mobilization of more CD34(+) cells (2.7-fold/kg/apheresis), erythroid burst-forming units (1.8-fold/kg/apheresis), and colony-forming units-granulocyte-macrophage (2.2-fold/kg/apheresis) compared with regimen G given to the same patients (n = 46; paired t test, P<.01 for all comparisons). Compared with regimen G, regimen C resulted in better mobilization, whether it was given first (P =.025) or second (P =.02). The ability to achieve a target collection of > or =2x10(6) CD34(+) cells/kg using two leukaphereses was 50% after G1 and 90% after C1. Three of the seven patients in whom mobilization was poor after G1 had > or =2x10(6) CD34(+) cells/kg with two leukaphereses after C2. In contrast, when regimen G was given second (G2), seven out of 10 patients failed to achieve the target CD34(+) cell dose despite adequate collections after C1. Thirty percent of the patients (nine of 29) given regimen C were admitted to the hospital because of neutropenic fever for a median duration of 4 days (range, 2 to 10 days). The higher cost of regimen C was balanced by higher CD34(+) cell yield, resulting in equivalent charges based on cost per CD34(+) cell collected. CONCLUSION: We report the first clinical trial that used a cross-over design showing that high-dose cyclophosphamide plus G-CSF results in mobilization of more progenitors then GM-CSF plus G-CSF when tested in the same patient regardless of sequence of administration, although the regimen is associated with greater morbidity. Patients who fail to achieve adequate mobilization after regimen G can be treated with regimen C as an effective salvage regimen, whereas patients who fail regimen C are unlikely to benefit from subsequent treatment with regimen G. The cross-over design allowed detection of significant differences between regimens in a small cohort of patients and should be considered in design of future comparisons of mobilization regimens.

CD34+ selection of hematopoietic blood cell collections and autotransplantation in lymphoma: overnight storage of cells at 4 degrees C does not affect outcome.

The purpose of this study was to investigate whether storing mobilized peripheral blood progenitor cell (PBPC) collections overnight before CD34+ selection may delay platelet count recovery after high-dose chemotherapy and CD34+-enriched PBPC re-infusion. Lymphoma patients underwent PBPC mobilization with cyclophosphamide 4 g/m2 i.v. and G-CSF 10 microg/kg/day subcutaneously. Patients were prospectively randomized to have each PBPC collection enriched for CD34+ cells with the CellPro CEPRATE SC System either immediately or after overnight storage at 4 degrees C. Thirty-four patients were randomized to overnight storage and 34 to immediate processing of PBPC; 15 were excluded from analysis due to tumor progression or inadequate CD34+ cell mobilization. PBPC from 23 patients were stored overnight, while 30 subjects underwent immediate CD34+ selection and cryopreservation. Median yield of CD34+ enrichment was 43.6% in the immediate processing group compared to 39.1% in the overnight storage group (P = 0.339). Neutrophil recovery >500 x 10(9)/l occurred a median of 11 days (range 9-16 days) in the overnight storage group compared to 10.5 days (range 9-21 days) in the immediate processing group (P = 0.421). Median day to platelet transfusion independence was 13 (range 7-43) days in the overnight storage group vs 13.5 (range 8-35) days in those assigned to immediate processing (P = 0.933). We conclude that storage of PBPC overnight at 4 degrees C allows pooling of consecutive-day collections resulting in decreased costs and processing time without compromising neutrophil and platelet engraftment after infusion of CD34+-selected progenitor cells. Bone Marrow Transplantation(2000) 25, 559-566.

Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy.

PURPOSE: Multipotential mesenchymal stem cells (MSCs) are found in human bone marrow and are shown to secrete hematopoietic cytokines and support hematopoietic progenitors in vitro. We hypothesized that infusion of autologous MSCs after myeloablative therapy would facilitate engraftment by hematopoietic stem cells, and we investigated the feasibility, safety, and hematopoietic effects of culture-expanded MSCs in breast cancer patients receiving autologous peripheral-blood progenitor-cell (PBPC) infusion. PATIENTS AND METHODS: We developed an efficient method of isolating and culture-expanding a homogenous population of MSCs from a small marrow-aspirate sample obtained from 32 breast cancer patients. Twenty-eight patients were given high-dose chemotherapy and autologous PBPCs plus culture-expanded MSC infusion and daily granulocyte colony-stimulating factor. RESULTS: Human MSCs were successfully isolated from a mean +/- SD of 23.4 +/- 5.9 mL of bone marrow aspirate from all patients. Expansion cultures generated greater than 1 x 10(6) MSCs/kg for all patients over 20 to 50 days with a mean potential of 5.6 to 36.3 x 10(6) MSCs/kg after two to six passages, respectively. Twenty-eight patients were infused with 1 to 2.2 x 10(6) expanded autologous MSCs/kg intravenously over 15 minutes. There were no toxicities related to the infusion of MSCs. Clonogenic MSCs were detected in venous blood up to 1 hour after infusion in 13 of 21 patients (62%). Median time to achieve a neutrophil count greater than 500/microL and platelet count >/= 20,000/microL untransfused was 8 days (range, 6 to 11 days) and 8.5 days (range, 4 to 19 days), respectively. CONCLUSION: This report is the first describing infusion of autologous MSCs with therapeutic intent. We found that autologous MSC infusion at the time of PBPC transplantation is feasible and safe. The observed rapid hematopoietic recovery suggests that MSC infusion after myeloablative therapy may have a positive impact on hematopoiesis and should be tested in randomized trials.

Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer.

PURPOSE: To determine whether occult tumor contamination of autologous bone marrow or peripheral-blood progenitor cells (PBPC) influences clinical outcome after high-dose chemotherapy in patients with stage IV breast cancer. PATIENTS AND METHODS: We used an immunocytochemical assay capable of detecting one tumor cell in 5 x 10(5) hematopoietic cells to analyze bone marrow and/or PBPC collections obtained from 57 consecutive women with chemotherapy-sensitive metastatic breast cancer who received high-dose chemotherapy. The influence of occult tumor on time to progression, overall survival, and first site of recurrence (old or new) was studied. RESULTS: Twenty-three of 57 (40%) patients received bone marrow (n=6) or peripheral-blood progenitor collections (n=17) that contained microscopic cancer. Median time to progression and overall survival were 9 and 22 months in patients who did not receive infused tumor cells, compared with 10 and 24 months, respectively, in those who received occult tumor (P=not significant [NS]). Worse survival, but not time to progression, was observed in six patients who received > or = 2/100,000 tumor cells. Regardless of whether occult tumor was infused, the majority of relapses occurred in prior, rather than new sites of disease. Three patients who received stem-cell products contaminated by microscopic breast cancer remain free from progression at 21+, 47+, and 52+ months. CONCLUSION: Microscopic tumor was frequently detected by immunocytochemistry in hematopoietic stem-cell products, but did not predict for inferior treatment outcome in this cohort of patients with metastatic breast cancer. Quantitative information regarding infused tumor burden may have prognostic significance.

Group B streptococcal bacteremia in adults at Hartford Hospital 1991-1996.

Invasive disease due to Group B streptococci has been increasingly recognized as a problem in chronically ill adults. We studied all adults presenting with bacteremia due to Group B streptococci at Hartford Hospital over a period of more than five years. Fifty-nine episodes of septicemia occurred with a mortality rate of 15.3%. Markers for mortality included cirrhosis, azotemia, transaminase elevation, respiratory distress on admission, and ionized hypocalcemia Although commonly thought of as a maternal and pediatric pathogen, nonpregnant, chronically ill adults make up the vast majority of patients with Group B streptococcal sepsis.

Noxious fumes in a medical center: chemical and psychological aspects.

A group of operating room personnel at a medical center in Connecticut reported severe respiratory irritation manifested by either proxysmal cough or throat irritation suggestive of a noxious fume exposure, 13 April 1994. However, persistent complaints on 14 April 1994 were significantly different and more suggestive of a psychological reaction. By careful interviewing, physical examination, toxicological assays, and epidemiological investigation, the true nature of a mixed physiological and psychological episode was delineated. Enlightened management policy enabled rapid restoration of return to work with minimal economic loss.

Autologous CD34+ cell transplantation for patients with advanced lymphoma: effects of overnight storage on peripheral blood progenitor cell enrichment and engraftment.

In order to demonstrate the feasibility of mobilization, enrichment and engraftment of autologous peripheral blood CD34+ cells in patients with relapsed lymphoma, 59 peripheral blood progenitor cell (PBPC) collections from 21 patients were enriched for CD34+ cells using CEPRATE SC (CellPro, Bothell, WA, USA) immunoaffinity column. Following high-dose chemotherapy, a mean of 17 x 10(8) (range, 3-34) nucleated cells/kg containing 8.7 x 10(6) (0.3-26) CD34+ cells/kg were re-infused. Blood cell recovery in these patients was compared to engraftment capacity of unenriched PBPCs in a cohort of lymphoma patients treated with an identical high-dose chemotherapy regimen. Neutrophil and platelet engraftment was rapid in both groups including five patients who received < or = 1 x 10(6) CD34+ cells/kg. After infusion of CD34+ enriched cells, neutrophils exceeded 0.5 x 10(9)/l in 11 (8-14) days and platelets exceeded 20 x 10(9)/l (untransfused) in 15 (9-39) days. In order to optimize the immunoaffinity column utilization we stored the first PBPC collections overnight at 4 degrees C and combined them with the next day's collection prior to the CD34+ enrichment procedure in 11 patients. This maneuver resulted in a significant decrease in the CD34+ cell recovery (resulting in reinfusion of a mean of 42% less CD34+ cells). Although overnight storage did not affect neutrophil engraftment, platelet engraftment was prolonged in this group of patients even when > 2.0 x 10(6) CD34+ cells/kg were re-infused. The overnight storage procedure should be further evaluated for its effects on the CD34+ immunoaffinity enrichment procedure, megakaryocyte progenitors and platelet engraftment. We conclude that CD34+ cells enriched from peripheral blood result in rapid engraftment after high-dose chemotherapy in patients with advanced lymphoma that is comparable to that of patients receiving unenriched PBPCs.

Infection control concepts in critical care.

Patients with critical illnesses requiring aggressive medical intervention are at risk of acquiring serious nosocomial infection that may lead to increases in medical expenditures, morbidity, and mortality. Infection control in this population entails continuous surveillance for hospital-acquired infection, with investigation of outbreaks. Policies for effective antibiotic utilization, disinfection of medical devices and hospital environment, and patient isolation may limit nosocomial infection in this population. Finally, an effective infection control program should protect the health care worker from hospital-acquired infections through educational programs, routine health surveillance, vaccinations, and post-exposure care.

A phase II multicenter trial of high-dose sequential chemotherapy and peripheral blood stem cell transplantation as initial therapy for patients with high-risk non-Hodgkin's lymphoma.

The purpose of this study was to evaluate the safety and feasibility of front-line high-dose sequential (HDS) chemotherapy with peripheral blood stem cell (PBSC) transplantation in patients with newly diagnosed high-risk non-Hodgkin's lymphoma (NHL). Thirty-two patients with high-risk NHL (defined by the age-adjusted international index) underwent HDS chemotherapy followed by PBSC transplantation and consolidative radiotherapy. Twenty-eight patients (88%) had intermediate/high grade NHL and four patients (12%) had small noncleaved or lymphoblastic lymphoma. Twenty-four patients were classified as high-intermediate-risk (two risk factors) and eight patients were classified as high-risk (three risk factors). The five phases of HDS (see Fig. 1) consisted of Phase I (adriamycin, vincristine, and prednisone); Phase II (cyclophosphamide, filgrastim [G-CSF], and PBSC harvest); Phase III (methotrexate, leucovorin, vincristine; Phase IV (etoposide, filgrastim [G-CSF]); and Phase V (mitoxantrone, melphalan, autologous peripheral blood stem cell infusion, and filgrastim [G-CSF]). Radiation therapy was given to sites of previous bulk disease, 2400 cGy, (D + 30-100)]. Toxicity, engraftment, hospital utilization, overall survival, and relapse-free survival were evaluated. The high-dose sequential chemotherapeutic regimen was well tolerated. Treatment-related mortality was 6.25% with two deaths occurring secondary to sepsis and one death was caused by progressive disease. The major toxicity in Phase I-IV was grade 3 nausea/vomiting. The major toxicity in Phase V was grade 3 or 4 nausea/vomiting and mucositis. The median follow-up is 18.8 months (range 4-44 months). The overall survival (OS) and relapse-free survival (RFS) at 18 months for all patients were 78% (95% CI 37-90%) and 67% (95% CI 46-88%), respectively. The OS at 18 months for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 82% (95% CI 65-98%) vs. 30% (95% CI 0-86%) (p = 0.0059). One patient in this latter group remains alive at 6 months follow-up. The RFS for all patients, excluding the four patients with either small noncleaved or lymphoblastic lymphoma, was 78% (95% CI 58-97%) vs. 0% (95% CI 0-0%) (p = 0.0004). High-dose sequential chemotherapy with initial PBSC transplantation is well tolerated and appears effective in high-risk NHL. Superior results were noted in patients with intermediate grade versus those with small noncleaved or lymphoblastic NHL.

Erythroid burst-forming units (BFU-E) predict hematopoietic recovery after peripheral blood progenitor cell transplantation in patients with advanced breast cancer.

In 29 consecutive heavily pretreated stage IV breast cancer patients, we analyzed patient factors and in vitro characteristics of peripheral blood progenitor cell (PBPC) collections that might correlate with the speed of hematopoietic recovery after autologous transplantation. PBPC collections were assessed for total number of mononuclear cells infused/patient weight in kg and hematopoietic progenitor cell content using in vitro colony-forming assays. In these patients, who received PBPC as the sole hematopoietic support after myeloablative chemotherapy, the number of erythroid burst-forming units (BFU-E) infused correlated significantly with both time to neutrophil (P = 0.008) and platelet (P = 0.0001) recovery and was a better predictor of hematopoietic recovery than number of CFU-GM administered. By day 75 after transplantation, six patients with poor BFU-E yields failed to engraft platelets. Our data suggest that the number of BFU-E infused correlate with time to hematopoietic engraftment and may predict failure of platelet engraftment in heavily pre-treated patients.

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.

Severe acute graft-versus-host disease of conjunctivae after allogeneic blood progenitor cell infusion.

A 37-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia received allogeneic bone marrow transplants after first and second relapses from different HLA-identical brothers. After a third relapse, blood progenitor cells from one of the brothers were infused after six doses of cytarabine 1.5 g/m2 in an attempt to induce a graft-versus-leukemia effect. Seven weeks after the infusion, the patient developed delayed but severe acute graft-versus-host disease (GVHD) including the unusual manifestation of conjunctival involvement.