cGVHD is the most serious and common long-term complication of this allogeneic transplantation, occurring in 30-70% of patients surviving more than 100 days. cGVHD is associated with a high degree of morbidity and mortality and remains a major cause of late death. Initial therapy involves systemic corticosteroids which can contribute to further complications. In cases where steroids are ineffective or poorly tolerated, effective therapeutic options are limited. Anecdotal reports of myeloma patients treated with bortezomib after transplantation have shown improvement in cGVHD. We have begun a trial of bortezomib in patients with steroid-refractory cGVHD. Patients receive 1.6 mg/m2 q wk x 4 followed by one week of rest, for up to six cycles. To date 9 patients have been entered on trial and 5 have completed between 2 and 4 cycles. The treatment has been well tolerated with no grade 3 or higher adverse events (AE). AE have been grade 1-2 nausea (3), grade 1-2 diarrhea (6) grade 1-2 fatigue (4), one grade 2 transient neuropathy has been reported. There have been 3 treatment delays (1 patient) and dose reduction due to decreased hemoglobin and one due to transient neuropathy. Subjective improvement has reported in 6 of the first 8 patients, Improvement in general well-being has been noted as early as the first treatment. Two patients have had improvement in severe long standing sclerotic changes, including the ability to extend fingers that had long been contracted. Average Rodnan scores on 5 patients with sclerosis completing 2 or more cycles of therapy decreased from (31±9.6 to 13.8±7.5) One patient with non-healing suppurating lesions of his lower extremities has shown marked healing, another has significant decrease in chronic diarrhea. Weekly bortezomib for cGVHD appears to be well tolerated and results in early improvement in long standing refractory disease. Our plan is to enroll twenty-five patients to determine if these encouraging findings are sustainable.

All prospective autologous and allogeneic progenitor cell recipients and allogeneic donors must undergo pre-HSCT evaluation. Collection of defined elements of the evaluation process in real time with frequent updates requiring daily communication between physicians and HSCT staff is challenging, especially in a large HSCT program. Efficient data collection and management of pre-HSCT evaluation data allows inpatient and outpatient personnel the ease of accessing useful information on a patient in a quick and efficient manner, and should result in high quality of data for patient registration to CIBMTR. The customized PDI application developed at Baylor University Medical Center (BUMC) provides a user-friendly web-enabled database containing pre-HSCT patient and donor information, able to detect and flag deviations to standard of care. The PDI is available and accessible through the BUMC Intranet, in a password protected environment. Authorized users are granted different levels of access. The PDI also has a user tracking capability with user tracking being recorded each time it is accessed. The pre-HSCT evaluation process, data management and patient pre-registration with the CIBMTR have been supported by data collected, stored and accessed through the PDI. Physicians and authorized HSCT staff have access to pre-HSCT evaluation information regarding patients and donors undergoing blood and marrow transplantation. Examples of available information include: demographic information, diagnosis, disease markers, staging studies, prior treatments, comorbidities, organ function studies, infectious disease testing , HLA typing, and psychosocial summary. As physicians and designated HSCT staff enter pre-transplant evaluation data at specific time points, it goes through a logical algorithm that detects and generates deviations to standard of care and flags them. The PDI produces a comment box next to the flagged deviation for the physicians to enter a justification for the deviation so that the patient can proceed with a HSCT. Use of the PDI results in a better coordination of the pre-transplant evaluation process. It allows the data management staff access to accurate pre-HSCT information useful to register patients with the CIBMTR. Most of all it helps us ensure better quality and completeness of pre-HSCT evaluation data useful for statistical outcome analysis.

Oral mucositis (OM) is a commonly occurring side effect in patients (pts) undergoing AHSCT. Velafermin, recombinant human fibroblast growth factor-20, is under investigation for the prevention of severe OM. Previous studies demonstrated that velafermin at 30 mcg/kg was well tolerated and was effective in reducing the incidence of severe mucositis. The primary objective of this multicenter, randomized, double-blind, placebo controlled study was to confirm safety and efficacy of 30 mcg/kg velafermin for prevention of severe OM incidence (grade 3/4 OM based on the WHO grading system). The secondary objective was to evaluate safety and efficacy of 10 and 60 mcg/kg doses to better define the therapeutic range. Pts were randomized to receive placebo or velafermin at 30, 10 or 60 mcg/kg in a 3:3:1:1 ratio 24–36 hrs after stem cell infusion. Randomization was stratified by study center and OM risk factors identified from the previous placebo controlled study in a similar population including conditioning regimen and body mass index (BMI ≥30). Pts with multiple myeloma or lymphoma (≥18 y.o.) receiving ≥2X106 /kg CD34+ cells following chemotherapy with or without Total Body Irradiation (TBI) were eligible. OM status and safety data were collected for 30 days post treatment while mortality and disease progression were followed for 1 yr. An interim analysis by a data monitoring committee (DMC) was planned to assess safety and efficacy after 50% of pts completed the 30 day treatment period. A total of 390 pts who received melphalan (200 mg/m2) (n=239), BEAM (n=129), TBI (n=15), or other (n=7) were randomized and 384 pts were treated. The study drug was well tolerated in general and no pts discontinued study due to drug-related adverse events. There were 93 serious adverse events (SAEs) in 78 (20%) pts and no drug-related death was reported. Five infusion-related SAEs were reported including vasovagal episode (2), syncope (2), and anaphylactoid reaction (1). All 5 episodes occurred on the day of study drug infusion and resolved on the same day with no sequelae. Based on review of the results from the interim analysis, which included safety and efficacy data from 200 pts, the DMC recommended that the study continue to completion as planned. The last pt has completed the 30 day study period. The un-blinded results of the OM efficacy endpoints from velafermin treated groups or placebo as well as 30-day safety information from all pts will be reported.

7064 Purpose: To evaluate the efficacy/safety of a novel AML regimen in elderly patients with heart disease or in patients with a contraindication to ‘standard‘ anthracycline-containing regimens. Patients and Methods: Phase II, open-label design. Eligible pts had elderly de-novo or relapsed AML or would not benefit from 7+3 or simlar therapy. Treatment was CLOF 40 mg/m 2 , Ara-C 1,000 mg/m 2 . (d1–5). Results: Patients were accrued and treated from April 2005 through Oct 2006. All pts signed IRB-approved consents. The median age was 67 years (range 38–82 years). Twenty (67%) subjects had received at least one prior cytoxic regimen (excluding 5-AZA). Significant cardiovascular (history of MI, bypass grafting, cardiomyopathy) was present in 43% (13/30) prior to therapy. Thirty pts were enrolled and all recieved at least one day of therapy. 1 pt died within 24 hours of starting treatment due to disease progression. Of the remaining, 29/30 received at least one complete cycle of therapy and 5 received 2 cycles. None received more than 2 cycles. Toxicities were greater in those receiving a second cycle. Grade 4 neutropenia developed in all patients. There were no cases of regimen-related cardiac toxicity. Most patients had some degree of edema and third-spacing syndrome. Several developed a significant but reversible acral rash. 25 patients survived >28 days and are evaluable for hematologic response. The histologic response rate (RR) is 68% (17/25) consisting of 14 (56%) complete remissions (marrow blasts <5%) and 3 (12%) partial responses (PR). There were 13 subjects with known cytogenetic abnormalities, 1 favorable and 12 unfavorable. Complete cytogenetic remissions (CytoCR) occurred in 4 of those patients, by chromosome analysis and/or FISH. Durable remissions and low toxicity allowed some patients to proceed to nonablative allogeneic stem cell transplantation. Conclusion: Clofarabine and Ara-C is an active and well tolerated regimen in myeloid malignancies including “elderly AML” a distinct entity usually associated with poor response rate and high treatment-related toxicities. Other drug combinations with clofarabine are ongoing in hematopoietic transplant and other high risk subgroups. No significant financial relationships to disclose.

PURPOSE: To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in adult patients with refractory or relapsed acute myeloid leukemia and in selected elderly patients with untreated AML and heart disease.

Introduction: Low risk, curative therapy for patients with multiple myeloma remains elusive. Autologous stem cell transplant remains the standard of care for newly diagnosed multiple myeloma. Mobilization of adequate CD34+ cells can be a difficult task, especially in patients who have been heavily pretreated. We have compared the three mobilization regimens utilized at our facility and the subsequent CD34+ collections. Background: Standard chemotherapy is effective in maintaining control of multiple myeloma, however none has proven curative. Several trials have indicated that tandem or double autologous transplants may provide a significant benefit for overall survival and event free survival. When double transplants are planned, especially for patients who are heavily pretreated, collection of adequate CD34+ cells can prove to be challenging. Methods: 217 patients with multiple myeloma whose treatment plan included either a single or double autologous transplant were evaluated retrospectively. Data have been collected from January 1999 to March 2005. Mobilization regimens utilized were etoposide/cyclophosphamide+GCSF, 60 patients; cyclophosphamide+GCSF, 34 patients; and GCSF alone, 123 patients. Peripheral blood stem cells were collected following standard institutional procedures utilizing the Cobe Spectra apheresis machine. Standard CD34+ cell dose target for a single transplant was >2.0 × 106/kg. Results: Average and median CD34+ cell dose collected for patients receiving GCSF alone was 24.05 × 106/kg and 6.3 × 106/kg; cyclophosphamide+GCSF 13.28 × 106/kg and 9.75 × 106/kg; etoposide/cyclophosphamide+GCSF 39.98 × 106/kg and 30.4 × 106/kg. The average number of collections required for each regimen was 2.11 days for GCSF, 1.76 days for cyclophosphamide+GCSF, and 1.4 days for etoposide/cyclophosphamide+ GCSF. Conclusions: Etoposide/cyclophosphamide+GCSF mobilization regimen is highly effective in mobilizing large numbers of CD34+ cells in multiple myeloma patients making double or tandem transplants a viable treatment option. Introduction: Low risk, curative therapy for patients with multiple myeloma remains elusive. Autologous stem cell transplant remains the standard of care for newly diagnosed multiple myeloma. Mobilization of adequate CD34+ cells can be a difficult task, especially in patients who have been heavily pretreated. We have compared the three mobilization regimens utilized at our facility and the subsequent CD34+ collections. Background: Standard chemotherapy is effective in maintaining control of multiple myeloma, however none has proven curative. Several trials have indicated that tandem or double autologous transplants may provide a significant benefit for overall survival and event free survival. When double transplants are planned, especially for patients who are heavily pretreated, collection of adequate CD34+ cells can prove to be challenging. Methods: 217 patients with multiple myeloma whose treatment plan included either a single or double autologous transplant were evaluated retrospectively. Data have been collected from January 1999 to March 2005. Mobilization regimens utilized were etoposide/cyclophosphamide+GCSF, 60 patients; cyclophosphamide+GCSF, 34 patients; and GCSF alone, 123 patients. Peripheral blood stem cells were collected following standard institutional procedures utilizing the Cobe Spectra apheresis machine. Standard CD34+ cell dose target for a single transplant was >2.0 × 106/kg. Results: Average and median CD34+ cell dose collected for patients receiving GCSF alone was 24.05 × 106/kg and 6.3 × 106/kg; cyclophosphamide+GCSF 13.28 × 106/kg and 9.75 × 106/kg; etoposide/cyclophosphamide+GCSF 39.98 × 106/kg and 30.4 × 106/kg. The average number of collections required for each regimen was 2.11 days for GCSF, 1.76 days for cyclophosphamide+GCSF, and 1.4 days for etoposide/cyclophosphamide+ GCSF. Conclusions: Etoposide/cyclophosphamide+GCSF mobilization regimen is highly effective in mobilizing large numbers of CD34+ cells in multiple myeloma patients making double or tandem transplants a viable treatment option.

One year results from the development and utilization of a unified strategic business plan for marketing Blood and Marrow Transplant Services' Outpatient Clinic. The goal is to increase awareness of outpatient transplants and increase referrals. This is a follow-up from the 2003 Tandem BMT meetings. Blood and Marrow Transplant Services, PLLC is a subsidiary of Texas Oncology, P.A. The outpatient clinic recently doubled in size to 14,000 square feet in capacity with 6 private rooms, 16 infusion chairs and 15 exam rooms. Charged with the goal of increasing awareness of outpatient transplants and referrals, clinic administration developed a strategic plan through surveying physicians, patients and clinic personnel. After one year of this plan being in place, we now have results that show the strategic plan streamlined the referral process, increased awareness with Managed Care plans, and assisted with the streamlining of the Outpatient Transplant Clinic Operations. The main components of the plan include: BMT Outreach Programs to key physicians in regionBMT Transplant Managed Care Contracting initiativesCommunications Plan (Publications, Conferences, PR, Advertising, Internet)Clinic Operations Plan The plans include how we communicate internally and externally. This plan includes the development of our outreach program for referring physicians. The outreach program gives easy access to our BMT physicians for consultation and to gain answers to referring physician's questions. A goal of this program will show the cost-effectiveness of the outpatient program to the insurance/payer community. Our goal is to meet with all managed care and insurance companies to provide ongoing education on blood and marrow transplant services available on an outpatient basis.

Poster Presentations -Session II confirmation in a randomized trial is needed it appears that Ambi-some® 1 mg/kg/d is an efficacious and cost-effective approach to empiric antifungal therapy in patients with prolonged neutropenia and fever. 247

Autologous HCT patients often have poor oral intake for 2-4 weeks post transplant. To compare outcomes between patients provided prophylactic total parenteral nutrition (TPN) or an oral diet (OD), 55 well nourished breast cancer/hematopoietic cell transplantation (HCT) patients were randomized to TPN (n = 27), beginning day -1, or OD (n = 28). Parameters studied include length of stay (LOS), engraftment, infections, survival, weight, anthropometrics, handgrip strength, and quality of life (QOL) In all, 50% of OD patients were given TPN due to poor oral intake for 10 consecutive days. No significant differences were found between the groups for any of the above parameters except weight and anthropometrics, which were better maintained in the TPN group than the OD group. Trends were seen for increased infections, more stable handgrip strength, and improved QOL in the TPN group vs the OD group. Prophylactic TPN did result in a more intact nutritional status and preservation of lean body mass post transplant but did not impact LOS or survival when compared to OD. For this reason, TPN should be reserved for autologous HCT patients with pretransplant nutritional depletion, complications post transplant, or prolonged poor oral intake. These results should not be extrapolated to allogeneic HCT patients but are likely applicable to other well nourished autologous HCT patients.

Poster Presentations -Session II transplantation (SCT) for lymphomas and the engraftment of donor immnnocompetent cells is essential.The height of host "immunological barrier" belongs to the major factors influencing engraftment.Some patients transplanted after non myeloablative regimens finally reconstituted their own immunocompetent cells because of insufficient immunosuppression and there has been no room for GvL effect.On the other hand, many pretrcated immunocompromised recipients developed severe complications due to unnecessary toxicity.11 patients with non-hodgkin lym pbomas (NHL -8x) and chronic lymphatic leukemia (CLL -3x) underwent non-myeloablative allogeneie SCT fronl sibling donor.No one of them was in complete remision (CR) before SCT.The recipients with the pretransplant level of CD3+ cells below than 0, 5x10 9/L were grafted after conditioning combined flndarabin (125rag/m2) and cyclophosphamide (120mg/kg).Those ones with CD3+ cells above 0, 5x10 9/L underwent SCT after fludarabin and melphalan (140rag/m2), fludarabin, melphalan and ATG (40mg/kg)or fludarabin, cyclophosphamide and ATG.The "graft versus host disease" (GvHD) prophyla~s consisted of cyclosporine A (CsA) only or CsA combined with the short-course of methotrexate (MTX).Donor chilnerism was evaluated in T-cell population at day +30, +60, +100 after SCT.CsA tapering depended on the grade of donor chimerism in T-cells. 10 patients (90, 0%) achieved complete donor chimerism in T-cells and sustained CR of their disease at the posttransplant follow-up period (median 134 days).6 recipient (54, 5%) developed GvHD.3 patients (27, 3%) died of transplant-related complications.The combination of fludarabin and cyclophosphamide (+/-ATG) was associated with significantly lower to, city and allowed sufficient engraftment of donor cells with effective immunological mmour control in severe immunocompromised hosts.The reduction of conditioningorelated to,city without the decrease of CR rate fully advocate the pretransplant evaluation of T-cell populations in recipients.