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/μL versus 160/μL; P < .001), CD34(+) cell yield on day 1 of collection (2.6 × 10(6)/kg versus 11.7 × 10(6)/kg, P ≤ .001), and total CD34(+) cell yield (7.5 × 10(6)/kg versus 16.6 × 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 × 10(6)/kg and ≥10 × 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.
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.
313 Introduction: Peripheral blood progenitor cell (PBPC) mobilization with intermediate-dose cyclophosphamide (3–4 gm/m2) (ID-CY) and G-CSF has been shown to be less toxic than high-dose CY (≥7 gm/m2) -based, and more efficacious than low-dose CY (LD-CY) (1–2 gm/m2) -based mobilization regimens in multiple myeloma (MM) patients following conventional induction regimens. However the relative importance of CY dose intensity in PBPC mobilization following novel induction regimens is not known. Herein we report comparative efficacy of PBPC mobilization in MM patients following novel induction chemotherapies, relative to CY dose intensity. Methods: This multicenter outcomes study includes 123 patients who underwent a planned, single autograft within 1-year of starting induction chemotherapy with novel chemotherapy agents (thalidomide, lenalidomide, bortezomib), from 2003–2010. Consecutive patients undergoing mobilization with ID-CY/G-CSF (3–4 gm/m2) (n=55) at one institution were compared against consecutive patients receiving LD-CY/G-CSF (1.5 gm/m2) (n=68) at a different transplant center. At baseline the two groups were compared for parameters predicting mobilization failure. In order to assess efficiency of PBPC mobilization, we evaluated peak peripheral blood (PB) CD34+ cell counts, CD34+ cell yield on day1 of collection, total CD34+ cell collection, and total number of apheresis sessions. Mobilization failure was defined as failure to collect ≥2 ×106cells/kg body weight. All patients with normal renal function received uniform conditioning with Mel200 (MEL140 if serum creatinine was >2 mg/dl). SPSS version 13.0 was used for statistical analysis. Results: At baseline, the ID-CY and LD-CY cohorts were well balanced respectively in terms of mean age (57-yrs vs. 59-yrs, p=0.3), gender (males; 66% vs. 58%, p=0.4), high-risk cytogenetics (p=0.6), prior radiation (34% vs. 18%, p=0.06), disease stage (p=0.5), number of prior therapies (p=0.5) and remission status (p=0.2). No difference was observed in the types of novel therapies received prior to transplant (p=0.2), except 22% of the patients received lenalidomide in LD-CY vs. 40% in the ID-CY group (p=0.04). Compared to LD-CY, ID-CY use was associated with higher median peak PB CD34+ cell count (35/ul vs. 160/ul, p<0.001), CD34+ yield on day 1 of collection (2.6 ×106/kg vs. 11.6 ×106/kg, p=<0.001), total CD34+ cell yield (7.7 ×106/kg vs. 24.9 ×106/kg, p=<0.001), and a trend towards fewer apheresis sessions (p=0.052). Three patients in the LD-CY group had mobilization failure, while no patient in the ID-CY group had mobilization failure. Significantly higher proportion of patients (27% vs. 3.6%, p=<0.001) were unable to collect >5×106/kg CD34+ cells in LD-CY group. Neutrophil engraftment was significantly faster (15.4 days vs. 9.9 days) in the ID-CY patients, likely because of higher infused CD34+ cell dose. Conclusion: In conclusion, compared with LD-CY, ID-CY produced a more robust PBPC mobilization, in all parameters analyzed. These data caution against the use of LD-CY containing mobilization strategy in MM patients undergoing stem cell collection following novel induction regimens. Disclosures: No relevant conflicts of interest to declare.
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.
the incidences of grade2-4 aGVHD (35.9% vs 31.6%, p 5 0.18) and cGVHD (29.3% vs 30.5%, p 5 0.67). However, the liver involvement of aGVHD was higher in recipients with HCV (13.9% vs 23.9%, p 5 0.031), while there was no differences in liver involvement of cGVHD (37.3% vs 45%, p 5 0.33) and VOD (10.7% vs 17.3%, p 5 0.17). Furthermore, the recipients with HCV had significantly higher non-relapse mortality (NRM; 25.9% vs 38.0% at 2 year, p\0.01) and poor overall survival (OS; 51.4% vs 41.1% at 2 year, p\0.01). Multivariate analysis revealed that HCV sero-positivity remained significant as a risk factor for NRM (HR 1.60, p\0.01) and OS (HR 1.34, p 5 0.016) after adjusting with gender, age, disease, and donor source. Proportions of patients who died due to hepatic failure (4.9% vs 14.3%) and bacterial infection (9.4% vs 18.2%) were significantly higher in recipients with HCV than in those without HCV. Conclusion: HCV sero-positivity was identified as a risk factor for poor survival in HSCT. In addition, we should carefully manage not only liver dysfunction but also bacterial infection in HCV positive patients.
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