Abstract 4317 Background: APL is widely accepted as a curable leukemia with most multi-institutional studies showing very low treatment related mortality. This is in contrast to treatment in clinical practice outside the study population where the treatment related mortality is higher. A few recent population based studies show that mortality maybe as high as 30% in APL patients during induction. A recent analysis of SEER data from 13 population-based cancer registries with 1400 APL patients in the US showed that 17% of all patients and 24% of patients greater than 55 years of age die within one month of diagnosis. Swedish registry data and Brazilian data also show this high mortality during induction. The most common causes of death are bleeding, infection, differentiation syndrome and multi-organ failure. Patients who survive induction have an excellent cure rate with few late relapses. Hence, decreasing early deaths is a high priority both at experienced as well as smaller centers with limited leukemia treatment experience in this highly curable disease. Methods: At Georgia Health Sciences University, between 7/2005 and 6/2009, 19 patients were diagnosed with APL. Seven patients (5 high-risk and 2 low-risk) died during induction resulting in an unusually high mortality rate of 37%. All patients who survived induction are still in remission at present. The high early death rate prompted us to develop a simple, 2 page treatment algorithm that focuses on quick diagnosis, prompt initiation of therapy, and proactive and aggressive management of all the major causes of death during induction. We also developed a network of physicians in smaller community based treatment centers and gave them access to our protocol and helped them manage these patients in the induction period with the hypothesis that this standardized treatment approach will result in decreasing induction mortality. Results: From 11/2010 to 7/2012, we treated 5 patients at GHSU and helped manage 4 patients at 2 outreach sites. The age range was 30 to 60; two patients were high-risk, 6 intermediate- and one low-risk. In the pre-algorithm cohort the cumulative survival was 63.1% at 1 year with all deaths happening within 31 days. In contrast, after the implementation of a standardized algorithm the cumulative survival was 100% with no deaths during the induction or subsequent follow-up period, log rank p-value=0.05, with a median follow-up of more than 4-years in surviving patients. Conclusions: While we recognize that this is a small cohort, our own experience and a similar approach pioneered by investigators in Brazil clearly shows that this centralized, algorithm-based management under the direct supervision of a leukemia expert can be an effective intervention to decrease early deaths in APL. Based on the Brazilian experience an international consortium was formed to reduce the mortality and interim data show a reduction in early mortality to 7.5% with this networking of treatment centers. We believe our experience warrants large scale implementation with development of a network of physicians and standardization of treatment in the United States to improve early outcomes in this highly curable leukemia. Disclosures: Awan: Allos Therapeutics: Speakers Bureau.

BK-virus induced hemorrhagic cystitis (HC) frequently affects patients undergoing allogeneic hematopoietic stem cell transplant (allo-HSCT) and results in significant morbidity and mortality. There are no existing guidelines to dictate clinical practice. We present our institutional data and recommend a clinical practice guideline that could potentially improve the outcomes of patients with BK-virus infections.

6573 Background: Recent reports suggest that approximately 30% of patients with APL die during induction. This has been confirmed in large population-based studies in Sweden and the US. A recent analysis of SEER data from 13 population-based cancer registries with 1400 APL patients in the US showed that 17% of all patients and 24% of patients greater than 55 years of age die within one month of diagnosis. The most common causes of death are bleeding, infection, differentiation syndrome and multi-organ failure. Patients who survive induction have an excellent cure rate with few late relapses. Hence, decreasing early deaths is a high priority both at experienced as well as smaller centers with limited leukemia treatment experience in this highly curable disease. Methods: At Georgia Health Sciences University, between 7/2005 and 6/2009, 19 patients were diagnosed with APL. Seven patients (5 high-risk and 2 low-risk) died during induction resulting in an unusually high mortality rate of 37%. All patients who survived induction are still in remission at present. The high early death rate prompted us to develop a simple, 2 page treatment algorithm that focuses on quick diagnosis, prompt initiation of therapy, and proactive and aggressive management of all the major causes of death during induction. We also made our treatment protocol available to smaller treatment centers and helped the treating oncologists manage the patient during the first few days after diagnosis. Results: From 11/2010 to 12/2011, we treated 4 patients at GHSU and helped manage 4 patients at 2 outreach sites. The age range was 30 to 60; two patients were high-risk, 5 intermediate- and one low-risk. There were no deaths during induction and all eight patients proceeded to consolidation treatment. Conclusions: While we recognize that this is a small cohort, our own experience and a similar approach pioneered by investigators in Brazil clearly shows this to be an effective intervention to decrease early deaths in APL. We believe our experience warrants large scale implementation of our protocol in an attempt to reduce early APL mortality.

Abstract 4468 Introduction: BK viuria is an important and frequent infection in the post-allogeneic hematopoietic stem cell transplant (allo-HSCT) setting that results in significant morbidity and mortality. Over the years our understanding of the disease process has improved significantly but treatment algorithms remain poorly defined and developed. A variety of anti-viral therapies have been utilized in conjunction with reduced immunosuppression with modest benefits. We therefore present our institutional data and recommend a clinical practice guideline that could potentially improve the outcomes of patients with BK-virus infections. Method: Our retrospective analysis included 75 consecutive patients who underwent allo-HSCT from 2001–2011. Data was collected on patients with PCR proven BK-viuria under existing IRB approved protocols. SPSS version 13.0 was used for statistical analysis. Kaplan-Meier method was used to calculate survival outcomes. Result: 12% (9/75) of all patients developed PCR proven hemorrhagic cystitis (HC). The median age of patients at transplant was 37-years (range 28–61). 77% were male. 66% had acute myeloid or lymphoblastic leukemia and the median number of prior therapies was three. 33% had a matched unrelated donor transplant while 66% received reduced intensity conditioning regimen and 33% received anti-thymocyte globulin (ATG). The mean CD34+ cell dose infused was 4.8×106/kg and the mean CD3+ cell dose was 8.6×1011/kg. Median days to neutrophil engraftment were 11 and for platelet engraftment were 14. The median ECOG performance status was 1 (range 0–2). The median time of onset of HC from day 0 of transplant was 44-days (range 4–158) and lasted for an average of 53-days (range 7–157). 33% patients were neutropenic at the onset of HC and the mean absolute neutrophil count was 4300/ul. Most common symptoms were dysuria in 66%, bladder spasms in 44% and urinary retention in 22%. All patients had received GVHD prophylaxis with methotrexate and tacrolimus and 77% were on concurrent steroids and mycophenolate. 88% of patients had concurrent acute graft-vs.-host disease (GVHD) at the time of HC. 88% also had concurrent CMV viremia and 11% had EBV viremia at the time of HC. 44% developed BK-viremia while 55% had BK-virus induced nephropathy defined as an increase of serum creatinine >1.5. Management approach was tiered into prophylaxis, symptomatic relief and anti-viral therapy. All patients received ciprofloxacin and 88% received intravenous immunoglobulin (IVIg). No single therapy component including reduced immunosuppression, cidofovir and leflunomide was independently identified as a more efficacious option (p>0.05) but of the patients who received cidofovir, 75% had resolution of symptoms and were able to clear the BK-viuria with the median duration of treatment of 4.5 weeks. Conclusion: Our analysis supports existing data that BK-virus induced HC is the result of multifaceted host and donor interactions and the concurrent use of immune altering therapies. To address the need of reduced morbidity and improved outcomes of this commonly encountered scenario in the post allo-HSCT setting, we have developed a multi-tiered approach that includes prophylactic intervention with ciprofloxacin for patients undergoing T-cell depleting regimens; symptomatic management with continuous bladder irrigation, pyridium and oxybutynin; and antiviral therapy with cidofovir and leflunomide in select subsets of patients. This approach will provide us a tool to uniformly manage our patients with BK-viuria and HC, and continually analyze and improve outcomes in a prospective manner. Disclosures: No relevant conflicts of interest to declare.

Peripheral blood progenitor cell mobilization with intermediate-dose cyclophosphamide (ID-CY) and granulocyte colony-stimulating factor (G-CSF) has been shown to be more efficacious, albeit more toxic, than low-dose cyclophosphamide (LD-CY) mobilization regimens in patients with multiple myeloma treated with conventional therapies. However, the relative importance of cyclophosphamide dose intensity in peripheral blood progenitor cell mobilization after novel induction regimens is not known. Here we report mobilization outcomes of 123 patients who underwent transplantation within 1 year of starting induction chemotherapy with novel agents. We compared consecutive patients undergoing mobilization with ID-CY/G-CSF (3-4 g/m(2)) at one institution (n = 55) with patients receiving LD-CY/G-CSF (1.5 g/m(2)) at a different transplantation center (n = 68). At baseline, the 2 groups were well balanced, except for more frequent previous lenalidomide use in the ID-CY group (P = .04). Compared with LD-CY, ID-CY use was associated with higher median peak PB CD34(+) cell count (35/mu L versus 160/mu L; P < .001), CD34(+) cell yield on day 1 of collection (2.6 x 10(6)/kg versus 11.7 x 10(6)/kg, P <=.001), and total CD34(+) cell yield (7.5 x 10(6)/kg versus 16.6 x 10(6)/kg; P <= .001). Six patients in the LD-CY group had mobilization failure, compared with no patients in the ID-CY group. A significantly higher proportion of patients in the LD-CY group (P < .001) were unable to collect >= 5 x 10(6)/kg and >= 10 x 10(6)/kg CD34(+) cells. Neutrophil and platelet engraftment were significantly faster in the ID-CY group, likely because of higher infused CD34(+) cell doses. In conclusion, compared with LD-CY, ID-CY produced a more robust peripheral blood progenitor cell mobilization and significantly reduced the rates of mobilization failure. These data caution against the use of LD-CY-containing mobilization strategies in patients with multiple myeloma undergoing stem cell collection after novel induction regimens. Biol Blood Marrow Transplant 18: 1128-1135 (2012) (C) 2012 American Society for Blood and Marrow Transplantation