Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) alternating with high-dose methotrexate-cytarabine has proven to be an effective regimen in the treatment of adult ALL. Addition of the anti-CD20 monoclonal antibody rituximab to standard chemotherapy regimens has shown significant benefit in the treatment of lymphoma and leukemia expressing CD20. There is minimal data describing addition of rituximab to hyper-CVAD in the treatment of CD20+ ALL. We report 8 patients with CD20+ ALL treated with rituximab and hyperCVAD. Disease subtypes were precurser B-cell ALL (6), CML in lymphoid blast phase (1), and Burkitt's lymphoma (1). In addition to the patient with CML, one additional patient was Philadelphia chromosome-positive. These two patients received imatinib mesylate 400 mg on days 1–14 of each treatment cycle. Rituximab was administered at a dose of 375 mg/m2 on day 1 of each cycle of chemotherapy. Six patients achieved a complete remission (CR) by bone marrow analysis; 1 patient had normalization of the hematologic picture and was assumed to have achieved a CR, however, this was not confirmed with a bone marrow assessment due to patient-specific concerns; and 1 patient achieved a partial response (PR) defined as more than 50% reduction in nodal/mediastinal disease with clearance of the bone marrow. Median progression-free and overall survival have not been reached. All surviving patients are also disease-free with a range of 2+ to 51+ months from initiation of therapy. All patients tolerated the addition of rituximab well and there were no deaths due to treatment complications. Three patients have expired due to relapse of disease (6, 9, and 12 month survival) and one patient expired because of infection following allogeneic transplant. Rituximab appears to be a reasonable addition to hyper-CVAD in the treatment of CD20+ adult ALL and should be considered as part of pre-transplant cytoreductive therapy for high-risk patients. Larger studies need to be done to further evaluate the response and survival rates.

6553 Background: Allogeneic stem cell transplantation is used to treat different types of hematologic malignancies. The target stem cell dose typically is based on the recipient’s ideal body weight (IBW) with CD34 dose of 2.0–5.0 ×106/Kg. The dose of CD3 in the infusate is typically not taken into account in a stem cell product, except in T-depleted transplantation. The dose of T-cells in peripheral blood stem cell collections has been found to be at least 10-fold more than that in a bone marrow harvest product. Combined CD4+ and CD25+ cells infused have been directly correlated with increased incidence of GVHD. Methods: This is a retrospective study reporting the correlation of the CD34 and CD3 doses of stem cell transplant with incidence of acute GVHD in 67 consecutive patients who were treated between 2003 and 2005. All patients were followed up for at least 100 days following the stem cell transplant. Results: Among the 67 patients, 35 patients developed acute GVHD, while 32 patients had no evidence of acute GVHD. The CD3 and CD34 doses did not correlate. The correlation coefficient was 0.14 (P value: 0.27). Using t-test, there was NO statistical difference between the mean CD34 dose when comparing the group of patients who developed acute GVHD with the group that did not develop acute GVHD (P value: 0.31). Those who developed acute GVHD (n = 35) received a mean CD3 dose of 41.9 × 107/kg IBW (95% CI: 35.9–47.9). Those who did NOT develop acute GVHD (n= 32) received a mean CD3 dose of 33.5 × 107/kg IBW (95% CI: 27.3–39.8). By using the t-test, the P value for the different means was 0.0575. However, using a CD3 dose cutoff value of 30 × 107/kg IBW, the incidence of acute GVHD was statistically significantly less among those who received CD3 dose < 30 × 107/kg IBW. The Chi Square P value was 0.04. Conclusions: In our series, CD3 dose less than 30 × 107/kg IBW was associated with reduced risk of acute GVHD (P value: 0.04). There was no correlation between CD3 and CD34 counts in peripheral stem cell product. In addition, the CD34 dose did not influence the incidence of acute GVHD. These data suggest that, in addition to considering CD34 dose required for engraftment in allogeneic transplant, the CD3 dose will need to be considered to try to minimize the risk of acute GVHD. No significant financial relationships to disclose.

Background: Bacterial resistance to antibiotics is an increasing problem and associated with significant morbidity and mortality. Patients undergoing HSC transplantation and treatment for hematologic malignancy are at high risk of infection. We evaluated whether rotating the empiric antibiotics for patients who develop neutropenic fever in this setting resulted in decreased emergence of resistant organisms and decreased vancomycin use. Methods: Within the BMTU, all patients with neutropenic fever were empirically treated with piperacillin plus gentamicin (intermittent dosing) from January 1999 to February 2002. From March 2002 through June 2004, 3 antibiotic regimens were cycled every 8 months in the empiric treatment of neutropenic fever: imipenem monotherapy, cefepime plus tobramycin (extended-interval dosing), and piperacillin/tazobactam plus tobramycin (extended-interval dosing). Levofloxacin was initiated as prophylaxis in March 2002 if the duration of neutropenia was expected to be> 10 days. For the time periods before (January 1999 to December 2001) and after (January 2002 to June 2004) the initiation of antibiotic cycling and levofloxacin prophylaxis, we retrospectively compared the rates of bacteremia (excluding coagulase-negative staphylococcus) and antimicrobial use. Results: The rate of gram-positive bacteremia was similar in the 2 periods (4.6 vs 4.8 episodes/1000 patient days; P= .87). However, there was an emergence of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and levofloxacin-resistant Streptococcus species during the period of antibiotic rotation and prophylaxis. Gram-negative bacteremia rates decreased significantly (4.8 vs 1.8 episodes/1000 patient days; P= .003), and Klebsiella species disappeared from culture isolates. After the initiation of antibiotic cycling, the rates of Pseudomonas isolates decreased (1.7 vs 0.7 episodes/1000 patient days; P= .09), and isolated strains were less resistant to ceftazidime and piperacillin. Vancomycin use decreased during the period of antibiotic cycling and prophylaxis (397 vs 289 defined daily dose/1000 patient days; P< .001). Conclusions: The introduction of antibiotic cycling and prophylaxis in our BMT unit was associated with a significant decrease in gram-negative bacteremia rates. Although there was no evidence of emerging resistance among the gram-negative isolates, there was an increased rate of MRSA and VRE bacteremia.

Granulocyte colony stimulating factor (G-CSF) is commonly used following autologous peripheral blood stem cell transplantation (PBSCT) to promote bone marrow recovery. However, the optimal timing of G-CSF in this setting is unknown. We randomized 23 patients undergoing autologous PBSCT for a variety of malignant disorders to G-CSF administration 5 μg/kg/day starting day +5 (Arm A) versus when white blood count (WBC) recovered to 0.2 x 109/L or 0.1 x 109/L for 2 consecutive days (Arm B). Results: All patients engrafted. The median time to absolute neutrophil count (ANC) > 1.0 x 109/L in Arms A and B was 12.1 vs. 12.8 days (p=0.77). There was no significant difference in number of days of temperature >38.3°C (4.3 vs. 4.4 days, p=0.71) or hospital stay (23.8 vs. 22.1 days, p=0.93) between Arms A and B respectively. The mean amount of G-CSF administered was 3210 μg/patient in Arm A vs. 2384 μg/patient in Arm B, a significant reduction (p=0.035). Conclusion: Waiting for early signs of engraftment after autologous PBSCT before starting G-CSF administration is associated with a decrease in amount of G-CSF administration by 25%, with no increase in days with fever, time to neutrophil recovery, or length of hospital stay.

systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. prophylaxis with fluconazole or low-dose amphotericin b reduces, but does not eliminate these infections. to determine which prophylactic agent is better, we performed a prospective randomized study. patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive fluconazole (400 mg/day p.o. or i.v.) or amphotericin b (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/μl. patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38°C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5–0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p < 0.05). approximately 44% of all patients were removed from prophylaxis for presumed fungal infection. proven fungal infections occurred in 4.1% and 7.5% of fluconazole and amphotericin-treated patients, respectively. proven fungal infections occurred in 9.1% and 14.3% of related allogeneic marrow recipients receiving fluconazole or amphotericin b, respectively, and 2.1% and 5.6% of autologous marrow recipients receiving fluconazole or amphotericin b, respectively (P > 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated. Bone Marrow Transplantation (2000) 25 , 853–859.

Macrophage inflammatory protein‐1α (MIP‐1α) is a chemokine that can inhibit the cell cycle progression of both primitive haemopoietic and epidermal progenitor cells. This property could potentially be exploited to attenuate both the myelosuppressive effects of chemotherapy as well as mucositis. We evaluated both the biological and clinical effects of BB‐10010, a genetically engineered variant of MIP‐1α, in patients with malignant lymphoma or breast cancer receiving high‐dose etoposide (VP 3.6 g/m2) and cyclophosphamide (Cy 200 mg/kg). 52 patients were randomized to one of three cohorts. Cohort A received no BB‐10010; cohorts B and C received 10 μg/kg and 100 μg/kg of BB‐10010, respectively. All patients received post‐chemotherapy G‐CSF. BB‐10010 was well tolerated. There were no significant differences between groups in recovery to an ANC > 0.5 × 109/l, 1 × 109/l or 1.5 × 109/l, the number of days with an ANC < 0.5 × 109/l, days to a platelet count >50 × 109/l or 100 × 109/l, or the incidence and severity of mucositis. There was no evidence of any effect of BB‐10010 on colony‐forming cell (CFC) or long‐term culture‐initiating cell (LTC‐IC) mobilization, cycling activity in the marrow or on chemotherapy‐induced changes in CFC or LTC‐IC number both of which were in the normal range by 22 d after completion of the chemotherapy. To our knowledge this is the first report of a myelointensive regimen having no apparent long‐term effect on the LTC‐IC compartment. In summary, BB‐10010 is safe when used in patients receiving high‐dose therapy but has no effect on reducing the toxicity of such therapy.