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.

Clostridium difficile-associated disease in human stem cell transplant recipients: coming epidemic or false alarm?

Clostridium difficile is the most common cause of nosocomial diarrhea in the United States and Europe, and is a cause of significant morbidity and mortality among hospitalized patients. A newly identified epidemic strain has been associated with many hospital outbreaks of C. difficile-associated disease (CDAD), raising the concern of an escalating burden of CDAD among at-risk patients. Hematopoietic SCT (HSCT) recipients are known to be at increased risk for a wide variety of infectious complications, including CDAD as a result of prolonged hospitalizations, exposure to broad-spectrum antibiotics, altered integrity of the intestinal mucosa and GVHD. The incidence of CDAD in the HSCT population has been reported as high as 20% in some large series. The frequency and seriousness of CDAD in this defined group as compared with the general hospital population, however, are not clearly delineated. We discuss the epidemiology and diagnosis of CDAD and review recent studies examining the risk factors and characteristics of CDAD in HSCT recipients. Finally, we provide a management algorithm for the diagnosis and treatment of CDAD at our institution.

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.

Transfer of the hematopoietic stem cell transplant patient to the intensive care unit: does it really matter?

We critically reviewed published English language literature and concluded that from 1998 onward the survival of hematopoietic stem cell transplant (SCT) patients who experienced intensive care unit (ICU) transfer has improved. The factors associated with increased mortality during ICU stay included increased patient age, allogeneic transplant, intubation/mechanical ventilation, multiorgan system failure (MOSF), presumed/documented infection, graft-versus-host disease, and higher APACHE and O-PRISM score at ICU transfer. This encouraging outcome trend reflects evolving advances such as use of recombinant hematopoietic growth factors, use of mobilized blood cells rather than marrow, protective strategies for acute lung injury and early goal-directed therapy for sepsis syndrome. Patient selection bias (which patients were transferred and which were not sent to an ICU) also plays a role in ICU survival rates. New strategies to improve upon SCT patient outcome include use of a scoring system to predict mortality, better therapies for MOSF and integration of ICU components and multispecialist involvement earlier in the clinical course to prevent severe complications such as respiratory failure. SCT recipients comprise a heterogeneous group; to further advance this field, prospective multicenter trials involving larger populations from many centers are needed to reduce the biases of retrospective and single-center reports.

Lowering the prophylactic platelet transfusion threshold: a prospective analysis.

The 20 x 10(9) /L threshold for prophylactic platelet transfusion may be unnecessarily high. Few prospective studies, however, in which other trigger values were tested have been published. In this study all hospitalized, thrombocytopenic adult hematology-oncology patients in our institution were prospectively evaluated daily for hemorrhage and platelet transfusion during a one year period; no patients were excluded for bleeding or infectious problems. By design, during the initial six-months (baseline period), the prophylactic platelet transfusion trigger was 20 x 10(9) /L; for the second six-months (study period) this threshold was changed to 10 x 10(9) /L. Patients studied during the two periods did not differ significantly in age, gender, diagnosis, blood or marrow transplant status, and duration of neutropenia. Compliance with the thresholds was 95.6% (baseline period) and 93.5% (study period). For patients with platelet counts under 20 x 10(9) /L, the mean use of platelet transfusions per patient per day was significantly lower in the study period (4.47) than in the baseline period (6.48; p<0.001). Both mean prophylactic (1.54/patient-day) and therapeutic (2.93/patient-day) platelet transfusions were reduced in the study period compared with the baseline period (2.26 and 4.22/patient-day, respectively). Hemorrhage was slightly reduced in the study period compared with the baseline period: major hemorrhage, 15.2% vs. 18.4% (p=0.014); minor hemorrhage, 63.6% vs. 70.1% (p<0.001). Thus, hemorrhage was not increased with the lower trigger level. A 10 x 10(9) /L prophylactic platelet transfusion threshold value is safe and effective.

Multi-purpose silastic dual-lumen central venous catheters for both collection and transplantation of hematopoietic progenitor cells.

Autologous peripheral blood progenitor cell (PBPC) transplantation frequently requires sequential placement and use of two separate central venous catheters: (1) a short-term, large-bore, stiff device inserted for leukapheresis, and after removal of that device, (2) a long-term, multi-lumen, flexible, Silastic catheter for administration of high-dose chemotherapy, re-infusion of hematopoietic cells, and intensive supportive care. We reviewed our recent experience with two dual-lumen, large-bore, Silastic multi-purpose ('hybrid') catheters, each of which can be used as a single device for both leukapheresis and long-term supportive care throughout the transplant process. Quinton-Raaf PermCath and Bard-Hickman hemodialysis/apheresis dual-lumen catheters were used as the sole venous access device in 112 consecutive patients who underwent autologous PBPC collection and transplantation. The catheter exit site was monitored three times a week, and lumen patency was assessed using clinical and radiologic techniques. Catheters were removed prematurely for persistent thrombus, positive blood cultures despite appropriate antibiotics, or mechanical dysfunction. There were no intra-operative or immediate post-operative complications relating to insertion. Thirty-two patients experienced catheter occlusion necessitating urokinase instillation. Persistent occlusive problems were noted in 16 patients, and in 10 patients the catheter had to be removed. Two exit site infections and 17 bacteremias occurred. Catheters had to be removed for persistent infection in two subjects and for mechanical problems in five others. Cost analysis comparing the hybrid catheters alone vs conventional devices revealed a charge of $4230 in patients with hybrid catheters vs. $7530 in those requiring a temporary non-Silastic dialysis catheter in addition to a flexible, long-term Silastic catheter. Hybrid, Silastic, dual-lumen, large-bore central venous catheters are safe, cost-effective and convenient multi-purpose venous access devices that may be used in the setting of autologous PBPC collection and transplantation. The rate of thrombotic, infectious and mechanical complications appears comparable to other central venous access devices.

Lack of utility of the lysis-centrifugation blood culture method for detection of fungemia in immunocompromised cancer patients.

We retrospectively compared the utility of a fungal isolation device (Isolator) versus conventional techniques for recovering fungal organisms from blood cultures obtained from neutropenic cancer patients. Positive cultures were deemed true pathogens, possible pathogens, or contaminants according to laboratory and clinical criteria. Fifty-three patients had 66 positive blood cultures for fungi, nine on multiple occasions. In 20 episodes true pathogens were recovered, 6 from broth medium alone, 4 from the Isolator system alone, and 10 from both systems. False-negative cultures were noted in 4 of 20 (20%) cases in which broth medium was used and in 6 of 20 (30%) cases in which the Isolator system was used. Possible pathogens were detected in 4 of 66 blood culture-positive cases. Forty-two positive cultures were considered contaminants, 1 collected from standard medium and 41 of 42 (98%) which grew only in Isolators. Eleven of 18 patients with true fungal infections expired as a result of infection, while 4 of 33 patients with a contaminant expired, none from a fungal cause. We do not advocate the routine use of Isolator tubes in the evaluation of the febrile, neutropenic patient due to the high rates of false positives and of contamination.

Microbiologic contamination of peripheral blood progenitor cells collected for hematopoietic cell transplantation.

BACKGROUND: Peripheral blood progenitor cells (PBPCs) rather than bone marrow are used increasingly to provide hematologic reconstitution when transfused after marrow-ablative chemotherapy. PBPCs often are collected via central venous catheters that have remained in place for long periods of time and that may become infected. STUDY DESIGN AND METHODS: The investigators reviewed their 5-year experience in collecting PBPCs for the prevalence of bacterial contamination. Except for cotrimoxazole therapy given to prevent Pneumocystis cariini pneumonia, patients were not given antibiotic prophylaxis. RESULTS: Each patient underwent a median of 7 (range, 2-21) PBPC collections; 0.2 percent (3/1040 collections) were culture positive for bacteria (two collections contained coagulase-negative staphylococci and one contained Serratia marcescens). All culture-positive collections were discarded; no PBPCs were culture positive at the time of thawing and transfusion. CONCLUSION: This contamination rate is below that previously reported for bone marrow harvests and platelet concentrate collections. Obtaining PBPCs through large-bore central venous catheters has not added to the risk of infection in transplant patients. A program of screening in vitro cultures and strict adherence to sterility techniques can result in very low microbiologic contamination and thus obviates the need for prophylactic antimicrobials in the PBPCs and in the patient.

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.

Laparoscopic liver biopsy to evaluate hepatic dysfunction in patients with hematologic malignancies: a useful tool to effect changes in management.

Hepatic dysfunction is common in patients who receive intensive chemotherapy and it is important to determine the etiology in order to institute appropriate therapy. The role of laparoscopic liver biopsy in patients with neutropenia, thrombocytopenia, or both was evaluated as a mean of making treatment decisions and as a determinant of clinical outcome. Laparoscopic liver biopsy was performed in 29 subjects who were receiving intensive cytotoxic therapy with or without bone marrow transplantation. One to three direct-vision laparoscopic liver biopsies were performed in each patient using a Tru-cut needle during general anesthesia. Platelet concentrate transfusions were usually given before, during, and immediately after biopsy. Bleeding was controlled with spatula electrocautery. Thirty-two biopsies were obtained in 29 patients. At the time of liver biopsy, white blood cell and platelet counts ranged from 0 to 14,300/microliters (median: 2500/microliters), and 1000 to 47,000/microliters (median: 20,000/microliters), respectively. Bleeding at the liver biopsy site was readily controlled during the procedure without clinical evidence of significant bleeding; no procedure-related complications were noted and no patients required re-exploration. All biopsies were informative and the lesions observed in 32 biopsies revealed graft-versus-host disease (n = 5), hepatic candidiasis (n =1), hepatic veno-occlusive disease (n = 3), cholestasis (n = 19), hemosiderosis (n = 26), toxic injury (n = 8), hepatic steatosis (n = 4), granuloma (n = 1), viral infection (n =1), and malignancy (n = 1). Laparoscopic liver biopsy has been proven to be an effective means of assessing the cause of liver dysfunction in patients who were thrombocytopenic and immunosuppressed. The diagnosis obtained at laparoscopic liver biopsy altered therapy in nine of 29 (31%) patients.

Delayed, transient encephalopathy after marrow transplantation: case reports and MRI findings in four patients.

Subacute encephalopathy developed in four patients within one to two months after undergoing high-dose chemotherapy and bone marrow transplantation or peripheral blood progenitor (stem) cell transplantation for breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. None of the patients had previously known neurologic disorders, central nervous tumor or infection. Two patients presented with generalized tonic, clonic seizures, and two with confusion and lethargy. In all patients lumbar puncture and CT scans of the brain were normal, while magnetic resonance imaging (MRI) demonstrated multifocal predominantly white matter lesions. Phenytoin therapy was given to the two patients with seizures and all four patients improved without specific therapeutic intervention. Repeat MRIs became normal within three months. We report a delayed and transient encephalopathy which appears to be a unique complication of high-dose cytotoxic chemotherapy. The corresponding brain lesions may not be appreciated on CT scans, suggesting an expanded role for MRI studies in patients who develop neurologic findings while undergoing high-dose cytotoxic therapy.

Reliability of automated platelet counts: comparison with manual method and utility for prediction of clinical bleeding.

The 20 x 10(9)/L (20,000/microliters) threshold for prophylactic platelet transfusion may be unnecessarily high. The widespread use of this threshold may reflect lack of confidence in the reliability of low platelet counts. We evaluated the performance of automated platelet counts and their relation to clinical bleeding. First, we prepared serial blood dilutions with "target" platelet counts from 2 to 40 x 10(9)/L. For the 48 measurements on 2 x 10(9)/L "target" dilutions, values of 1 or 2 x 10(9)/L were obtained with the Sysmex NE-8000 analyzer (mean 1.44 x 10(9)/L; SD 0.31 x 10(9)/L). Similarly, for 5 x 10(9)/L "target" counts, automated counts were 3-6 x 10(9)/L (mean 4.42 x 10(9)/L; SD 0.18 x 10(9)/L). Similar results were observed with all other "target" levels, with coefficients of variation (CV) from 6.39% to 7.71% with 10-40 x 10(9)/L "target" values. Secondly, we compared triplicate automated and manual platelet counts on thrombocytopenic patients with platelet counts from 4-30 x 10(9)/L. The triplicate automated platelet counts differed by no more than 5 x 10(9)/L among themselves, whereas the manual counts varied by as much as 30 x 10(9)/L. Mean platelet counts: automated, 14.40 x 10(9)/L (CV 10.12%); manual, 16.48 x 10(9)/L (CV 30.39%) (P = 0.038 for counts; P < 0.001 for CV). Finally, we prospectively evaluated bleeding in thrombocytopenic patients (1,809 patient-days of observation). Univariate and multivariate logistic regression analysis revealed highly significant correlations between the automated platelet count and major and minor bleeding manifestations. Thus, automated platelet counts are highly reliable and accurately predict clinical bleeding. The use of automated analyzers should facilitate improved prophylactic platelet transfusion protocols.

Acute cholecystitis after autologous bone marrow transplantation for acute myeloid leukemia.

BACKGROUND: We investigated the incidence of acute cholecystitis in patients with acute myeloid leukemia (AML) undergoing autologous bone marrow transplantation in complete remission. PATIENTS AND METHODS: Thirty-five consecutive acute myeloid leukemia patients were given oral busulfan 4 mg/kg/day for 4 days and IV cyclophosphamide 50 mg/kg/day for 4 days followed by reinfusion of autologous bone marrow purged with 4-hydroperoxycyclophosphamide. RESULTS: Five of 35 patients developed clinical evidence of acute cholecystitis, manifested by fever, nausea, vomiting, right-upper-quadrant pain, and abdominal guarding, within 18 days after autologous bone marrow infusion. Ultrasonography and CT scans of the abdomen supported the diagnosis of cholecystitis. Three patients underwent cholecystectomy, while two patients were treated medically; all recovered uneventfully. A review of 338 consecutive bone marrow transplant patients who underwent marrow transplantation for a variety of diseases and were treated with other high-dose cytotoxic regimens during the same time period revealed significantly fewer cases of cholecystitis, i.e. two, (p < 0.0001). CONCLUSIONS: Five of 35 AML patients undergoing autologous bone marrow transplant using busulfan, cyclophosphamide, and purged bone marrow developed evidence of acute cholecystitis. These findings suggest that the busulfan/cyclophosphamide preparative regimen may be associated with acute cholecystitis. The true incidence of this injury and its pathogenesis remain to be elucidated.

Maximum-tolerated doses of ifosfamide, carboplatin, and etoposide given over 6 days followed by autologous stem-cell rescue: toxicity profile.

PURPOSE: A phase I dose-escalation study of ifosfamide, carboplatin, and etoposide (ICE) with autologous stem-cell rescue (ASCR) was conducted to determine the maximum-tolerated dose (MTD) of ICE given over 6 days. PATIENTS AND METHODS: One hundred fifty-four patients with a variety of poor-prognosis malignancies received escalating doses of ifosfamide 6,000 to 24,000 mg/m2, carboplatin 1,200 to 2,100 mg/m2, and etoposide 1,800 to 3,000 mg/m2 divided over 6 days. Mesna was administered in a dose equal to ifosfamide. ASCR was performed 48 hours after the completion of ICE. The source of stem cells was bone marrow (BM) in patients without BM micrometastases and peripheral-blood stem cells (PBSC) in patients with BM micrometastases. Patients were evaluated for hematologic and nonhematologic toxicities, as well as response to therapy. RESULTS: The MTD of the ICE regimen is 20,100 mg/m2 of ifosfamide, 1,800 mg/m2 of carboplatin, and 3,000 mg/m2 of etoposide. The dose-limiting toxicities of ICE were CNS toxicity and acute renal failure. Additionally, reversible elevations of serum creatinine levels were noted in 29% of patients treated at the upper dose levels. Forty-six patients were treated at the MTD. Severe, reversible mucositis and enteritis were the major nonhematologic toxicities seen at the MTD (78% and 33%, respectively). The overall mortality rate was 8% for all dose levels (4% at the MTD). At the MTD, the median times to an absolute neutrophil count > or = 0.5 x 10(9)/L, to a platelet count > or = 20 x 10(9)/L, and to discharge were 18, 22, and 24 days, respectively. The overall response rate was 40% for 77 patients with assessable disease at the time of treatment. CONCLUSION: ICE is well tolerated, with acceptable hematopoietic side effects and predictable organ toxicity.

Hepatic dysfunction in patients with carcinoma who are severely thrombocytopenic and immunosuppressed.

BACKGROUND: The use of intensive cytotoxic drug therapy for malignant disorders often results in hepatic dysfunction. It is important to determine the cause of hepatic injury to institute appropriate therapy; however, neutropenia and thrombocytopenia may prevent performance of hepatic biopsy to establish a cause. STUDY DESIGN: We prospectively evaluated the cause of hepatic dysfunction using laparoscopic biopsy of the liver in 20 consecutive patients who were receiving intensive cytotoxic therapy, with or without bone marrow transplantation, or who were being treated for severe aplastic anemia. One to three direct-vision laparoscopic biopsies were performed in each patient during general anesthesia and bleeding was controlled with spatula electrocautery. Platelet concentrate transfusions were given before, during, and immediately after the biopsy. RESULTS: Platelet and leukocyte counts at the time of hepatic biopsy ranged from 1,000 to 83,000 per microL (median of 23,500 per microL) and zero to 14,300 per microL (median of 2,200 per microL), respectively. Nineteen of 20 patients had platelet counts of less than 68,000 per microL. Bleeding at biopsy site was controlled during the procedure without evidence of bleeding or complications after biopsy. Biopsy specimens revealed graft-versus-host disease (n = 2), hepatic veno-occlusive disease (n = 1), steatosis (n = 5), cholestasis (n = 19), hemosiderosis (n = 19), and granuloma (n = 1). CONCLUSIONS: In several patients, the knowledge derived from hepatic biopsy results altered the therapeutic strategy. The use of laparoscopic hepatic biopsy to assess the cause of hepatic dysfunction should be encouraged because it is a safe procedure, even in patients who are severely thrombocytopenic and immunocompromised.

Role of upper endoscopy in evaluation of upper gastrointestinal symptoms in patients undergoing bone marrow transplantation.

We reviewed our upper endoscopy (esophagogastroduodenoscopy, EGD) experience in a group of 65 consecutive patients receiving carmustine (BCNU) 600 mg/m2, cisplatin 200 mg/m2, VP-16 2400 mg/m2, and autologous bone marrow transplantation (BMT) for relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. Forty-one patients (33 with chest irradiation) underwent 48 EGDs for the following symptoms: upper gastrointestinal bleeding (melena and/or hematemesis) (12/48); persistent nausea and vomiting (7/48); odynophagia (25/48); and dysphagia (14/48). All patients who had dysphagia or odynophagia had endoscopic evidence of severe esophagitis, with confluent erosions or ulcerations. Gastrointestinal bleeding, which presented as melena or hematemesis, was caused by severe esophagitis in 11 of 12 patients. Yeasts were detected in 11/42 histological, or cytological specimens and were isolated in 4/26 cultures. No bleeding or infectious complications occurred in any patient as a result of the EGD procedure. We conclude that severe esophagitis documented by EGD is common in lymphoma patients receiving autologous BMT. Use of EGD, however, did not affect the decision to initiate empirical therapy with amphotericin B for persistent fever.

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.

High-dose cyclophosphamide-induced myocardial damage during BMT: assessment by positron emission tomography.

Despite its potential to cause myocardial damage, high-dose CY in doses up to 200 mg/kg is an integral part of preparative regimens for BMT. Conventional tests, such as an electrocardiogram or echocardiogram, have lacked sensitivity in prediction of cardiotoxicity in this patient population. We prospectively compared serial electrocardiograms and positron emission tomography scans before and after CY administration to investigate the possible changes in 13N-ammonia perfusion and 18F-2-deoxyglucose metabolism after CY administration in 12 consecutive patients undergoing BMT. Neither global nor regional changes in myocardial N-13 ammonia and 18-fluorodeoxyglucose were significant when compared with baseline studies and control studies (p < 0.05). In a single patient, however, a substantial increase in 13N-ammonia perfusion was seen in the inferior region simultaneously with electrocardiographic T wave inversions in the inferior leads. These changes may be due to alterations in myocardial blood flow or membrane permeability. PET scanning may be a useful adjunct in evaluating CY cardiotoxicity, although further investigations are needed to elucidate its role in clinical practice.

Corynebacterium striatum: a diphtheroid with pathogenic potential.

Although nondiphtherial corynebacteria are ubiquitous in nature and commonly colonize the skin and mucous membranes of humans, they rarely account for clinical infection. Corynebacterium striatum has rarely been reported to be a pathogen, causing pleuropulmonary infections and bacteremia in only immunocompromised or anatomically altered patients. We noted C. striatum to be the infecting pathogen or copathogen in six patients. To our knowledge, this report describes the first cases of C. striatum causing infection of exist sites of central venous catheters, thrombophlebitis associated with central venous catheters, conjunctivitis, and chorioamnionitis as well as a possible pathogen contributing to peritonitis and pyogenic granuloma. Unlike Corynebacterium jeikeium, which is highly resistant to beta-lactam agents, aminoglycosides, and quinolones, all strains of C. striatum isolated from the patients described in this report were susceptible to vancomycin and aminoglycosides, and all strains except one were susceptible to penicillin G, imipenem, and ciprofloxacin. C. striatum should be recognized as a potential pathogen in both immunocompromised and normal hosts in the appropriate circumstances, and appropriate antimicrobial therapy can quickly lead to resolution of infection.