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Introduction

Introduction:FLT3 internal tandem duplication (ITD) mutations have been historically associated with inferior outcomes in patients with acute myeloid leukemia (AML) and an intermediate risk status as per the European LeukemiaNet (ELN) 2022 guidelines. In 2017, the US FDA granted approval to midostaurin for frontline treatment and a year later, gilteritinib for use in relapsed/refractory (R/R) AML. These agents began to be widely used in our provincial leukemia program in early 2018 as per the label indications. In this study, we compared clinical outcomes for patients with FLT3-ITD mutated AML before and after this change in British Columbia.

Introduction: Lung involvement in chronic graft versus host disease (cGVHD) is an uncommon but potentially devastating complication with significant morbidity and mortality in patients who have received an allogeneic hematopoietic stem cell transplant (alloHSCT). Unfortunately, early detection remains difficult as early lung cGVHD tends to be asymptomatic or present with nonspecific symptoms such as cough or mild shortness of breath. In British Columbia (BC), Canada, routine pulmonary function tests (PFTs) have been employed in the screening of lung cGVHD in this population at an interval of every 3-4 months for the first 2-3 years after alloHSCT. However, it is unknown whether routine screening 1) improves detection of lung cGVHD, and 2) enables earlier intervention to lead to better outcomes. We aimed to assess the real-world outcomes of lung cGVHD screening and compared the characteristics and clinical results of patients who had lung cGVHD detected via routine PFT screening, versus those who were detected after development of symptoms.

Introduction:

White: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Introduction

Introduction:

No relevant conflicts of interest to declare.

Introduction:

Introduction: Post-remission therapy (PRT) for acute myeloid leukemia (AML) remains an area of debate. Autologous stem cell transplantation (AutoSCT) is listed as a possible PRT in patients with intermediate risk AML in the 2017 European Leukemia Network Recommendations. Our center has frequently performed AutoSCT for patients with AML and we aimed to retrospectively compare this strategy with allogeneic SCT (AlloSCT) and consolidation chemotherapy (CMT).

Song: Celgene: Honoraria, Research Funding; Janssen: Honoraria; Otsuka: Honoraria. Toze:Roche Canada: Research Funding. Gerrie:Roche Canada: Research Funding.

Gerrie: Roche Canada: Research Funding. Toze:Roche Canada: Research Funding. Song:Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding. Song:Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding. Nevill:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Song: Celgene: Honoraria, Research Funding; Otsuka: Honoraria; Janssen: Honoraria. Connors:Roche Canada: Research Funding. Toze:Roche Canada: Research Funding. Broady:Lotte & John Hecht Memorial Foundation: Research Funding. Gerrie:Roche Canada: Research Funding.

Toze: Roche Canada: Research Funding. Sehn:roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Scott:NanoString Technologies: Patents & Royalties: named inventor on a patent for molecular subtyping of DLBCL that has been licensed to NanoString Technologies. Villa:Lundbeck: Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria. Connors:NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Bristol Myers Squib: Research Funding; Seattle Genetics: Research Funding; Millennium Takeda: Research Funding. Song:Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding.

Background:

Background:

Background: Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma associated with translocations involving the c-MYC oncogene on chromosome 8. The 1996 Magrath regimen, CODOX-M/IVAC, showed a promising 2-year (y) event free survival (EFS) of 92% in 41 BL patients (pts), with additional trials of a dose-modified regimen demonstrating 2y overall survival (OS) 70-82% and 2y progression-free survival (PFS) 64% (Mead et al). A recent trial demonstrated that with addition of R, 3y OS and EFS were 83% and 75% (Ribrag et al). We sought to determine survival outcomes of adult BL pts in BC treated with CODOX-M/IVAC +/- R to evaluate the effectiveness of this regimen on a population basis.

Background

No relevant conflicts of interest to declare.

Introduction

No relevant conflicts of interest to declare.

Tyrosine kinase inhibitor (TKI) therapy has revolutionized the treatment of patients (pts) with chronic myeloid leukemia (CML). While allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for CML, it is now rarely utilized given the excellent long-term results with TKI treatment. Therefore, only a few reports are available detailing HSCT outcome for this pt population. The purpose of this study is to examine HSCT outcome for pts with CML who received TKI therapy and identify predictors of survival, relapse and non-relapse mortality (NRM). Between January 2002 and April 2012, 55 pts with CML underwent HSCT at the Leukemia/BMT Program of BC. Transplant indications were advanced disease at diagnosis (15), TKI resistance as defined by the ELN treatment guidelines (30), TKI intolerance (2), physician preferance (4). Four pts had not received TKI therapy during this time period and were excluded from further analysis. Of the 51 pts examined in this study there were 34 males and 17 females. The median age at HSCT was 45 years and the Sokal score at diagnosis was low risk or intermediate risk (22), high risk (28) and unknown (1). The median time from diagnosis to HSCT was 307 days. Therapy prior to HSCT was imatinib (IM) only (22); IM with chemotherapy (19); IM followed by dasatinib and/or nilotinib (10). Disease status at HSCT was first chronic phase (CP1) (19), accelerated phase (9), CP2 (19), CP3 (3), BP (1). Four pts had kinase domain mutations identified at HSCT. EBMT score was 1-4 (33), and 5-7 (18). HSCT was myeloablative in 48 pts [TBI-based (25); BuCY (23)] and reduced intensity in 3 pts. Stem cell source was bone marrow (8) or PBSC (43) from a HLA matched sibling (24), HLA matched unrelated donor (UD) (18) or mismatched UD (9). At a median follow-up of 5.9 years, 18 pts have relapsed [molecular (7), cytogenetic (1), hematologic (10)] and 16 pts have died [relapse (8), GVHD (3), infection (2) regimen related toxicity (2), cerebral hemorrhage (1)]. The overall survival (OS), event-free survival (EFS), relapse and NRM at 8 years was 68%, 46%, 41% and 23% respectively. The corresponding results for the 32 pts transplanted for TKI resistance/intolerance were 75% (OS), 52% (EFS), 39% (relapse) and 15% (NRM). In univariate analysis, disease status at HSCT (p=.0005), lower EBMT score (p=.04), complete molecular response (CMR) to HSCT (p<.0001), and Sokal score (p=.05) predicted for better OS. Donor (female) to pt (male) gender combination (p=.02), presence of cGVHD (p=.04) and CMR to HSCT (p<.0001) predicted for lower relapse. Predictors of NRM included disease status at HSCT (p=.008), lower EBMT score (p=.004) and CMR to HSCT (p<.0001). In multivariate analysis, CMR to HSCT remained an independent predictor of OS [odds ratio (OR) 43], EFS (OR 56), relapse (OR 29) and NRM. Donor (female) to pt (male) also remained an independent predictor of EFS (OR 6) and relapse (OR 3). In conclusion, HSCT remains an effective salvage therapy for pts with CML in the TKI era who present with advanced disease or resistance/intolerance to TKI therapy. Disease status at HSCT and achievement of CMR are strong predictors of OS, EFS, relapse and NRM.

No relevant conflicts of interest to declare.

Background:Chronic Lymphocytic Leukemia (CLL) patients (pts) have significant (sig) heterogeneity; survival ranges from decades to <5 years (yrs). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is promising treatment (tx) for high-risk pts. Ideally, predictive (pred) tools would allow clinicians to recognize such pts early, permitting transplant performance to maximize benefit and minimize procedure associated risk. Factors with significant (sig) pred capacity are not, however, entirely clarified. Moreover, limited studies compare CLL pts who have/have not received HSCT in terms of differences (diff) in characteristics (char) at diagnosis (dx), population (pop) composition and outcomes. This study evaluates pred factors for outcomes post allo-HSCT, and compares dx char between (bn) tx CLL pts who did /did not receive HSCT by evaluating a large pop-based CLL cohort (n= 1044) from the BC Provincial CLL Database (BCPCD).

Double-hit (DHIT) lymphoma is a heterogeneous group of non-Hodgkin lymphomas characterized by concurrent translocations involving MYC and BCL2 and typified by aggressive behavior and poor prognosis with only rare long-term survivors. There is no established treatment for DHIT lymphoma. Since 2003, the British Columbia Cancer Agency (BCCA) has adopted the use of intensive chemotherapy CODOX-M/IVAC combined with rituximab (R) followed by high-dose chemotherapy and hematopoietic cell transplantation (HSCT) as definitive treatment for DHIT lymphoma. In younger patients, an ablative matched sibling donor allotransplant (AlloSCT) is preferred over an autotransplant (AutoSCT). For all patients over the age of 60 years only AutoSCT is offered. Total Body Irradiation (TBI) is used as a part of the conditioning regimen for patients younger than 60 years of age. Here we report our provincial experience with this strategy, focusing on the ability to deliver this treatment and survival outcomes.The Leukemia/BMT Program of British Columbia database and the BCCA Lymphoid Cancer Database were searched to identify all patients diagnosed with non-Hodgkin lymphomas with concurrent translocation of MYC and BCL2 (DHIT lymphoma) diagnosed between January 2003-September 2012.27 cases of DHIT lymphoma were identified with the following characteristics: median age at diagnosis was 55.8 years (range 35.5-70.9 years); 19 (70%) were male; 26 (96%) patients had stage 3/4 disease; 16 (59%) had bone marrow involvement. All cases were HIV negative. Histological diagnosis based on the WHO 2008 classification were: diffuse large B-cell lymphoma (DLBCL) n=8 (30%); B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCL-U) n=17 (63%); B-cell acute lymphoblastic lymphoma (ALL) n=1; high-grade B-cell lymphoma, not otherwise specified (NOS) n=1. 13 cases (48%) were transformed from an underlying indolent B-cell lymphoma (12 follicular lymphoma, 1 low-grade B-cell lymphoma NOS). CODOX-M/IVAC + R was administered in 20 patients (74%). 7 patients received alternative chemotherapy regimen (5 R-CHOP, 1 R-CVP, 1 R-ICE) due to patient and/or physician preference. 14 patients (52%) underwent HSCT (7 AutoSCT, 7 AlloSCT), including 11 patients treated CODOX-M/IVAC + R pre-transplant, and 3 patients who received other therapy. 13 patients did not undergo HSCT: primary refractory disease n=7; patient preference n=2; deconditioning n=1; age > 65 and poor performance status n=3. The clinical status at time of transplantation was CR in 5 patients (19%), PR in 8 (30%), progressive disease in 1 (4%). The conditioning regimens included: cyclophosphamide/TBI n=6, VP-16/cyclophosphamide/TBI n=4, BEAM n=3, busulfan/cyclophosphamide n=1. At last follow-up, 15 (56%) patients have died, 14 from disease progression and 1 from complications of AlloSCT. 10 (37%) patients are alive and in remission and 2 patients are alive but have relapsed. 8 of 14 HSCT recipients (6 AutoSCT, 2 AlloSCT) remain alive and free of disease compared with 2 of 13 patients who did not receive HSCT; both disease free survivors received CODOX-M/IVAC + R. Median follow-up for living patients was 31 months (range 6.5-67.3 months). 2-year EFS and OS from the diagnosis of all DHIT lymphoma patients were 35% (95% CI 16%-54%) and 45% (95% CI 20%-65%), respectively. For patients who received CODOX-M/IVAC + R, the 2-year EFS was 37%. For patients who received CODOX-M/IVAC + R followed by SCT, the 2-year EFS was 43%. Patients with BCLU/ALL/High-grade lymphoma NOS had a 2-year EFS of 27% and patients with DLBL had a 2 –year EFS of 50%.Patients with DHIT lymphoma treated with CODOX-M/IVAC + R followed by SCT can have durable remissions. Regardless, progression during initial therapy prior to SCT remains a significant problem. Patients with DLBCL histology may have a more favorable outcome than those with BCLU. Savage: Eli-Lilly: Consultancy. Toze:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding. Sehn:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Gerrie:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Sutherland:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Villa:Roche: Honoraria, Research Funding; Lundbeck: Honoraria; Celgene: Honoraria. Song:Roche: Research Funding.

Biphenotypic acute leukemia (BAL) is a rare subtype of leukemia accounting for 1% to 4% of all acute leukemias. They are associated with unfavorable outcome especially in adult population when treated with standard chemotherapy alone. Management issues like type of induction therapy, consolidation strategies, and role of high dose chemotherapy with stem cell transplantation remain unclear.

Biphenotypic acute leukemia (BAL) is a rare subtype of leukemia accounting for 1% to 4% of all acute leukemias. They are associated with unfavorable outcome especially in adult population when treated with standard chemotherapy alone. Management issues like type of induction therapy, consolidation strategies, and role of high dose chemotherapy with stem cell transplantation remain unclear.A retrospective review of 28 patients (pts) with BAL who were treated in Vancouver between 1984 and 2012 was performed. Diagnoses were confirmed according to WHO 2008 guidelines by two hematopathologists who independently reviewed morphology, immunophenotyping and in few cases immunohistochemistry. Kaplan-Meier estimates were utilized for event free survival (EFS) and overall survival (OAS).There were 23 males and 5 females with a median age of 47 (range 17 - 75) years. Median white cell count (WCC) at presentation was 7.7 x 109(range: 0.9 to 192x109)/L. Immunophenotyping revealed “Myeloid + B-lymphoid” pattern in 13 pts (46.4%), “Myeloid + T-lymphoid” pattern in 13 pts (46.4%), “Myeloid + B-lymphoid + T-lymphoid” pattern in 1 pt (3.6%) and “T-lymphoid + B-lymhoid” pattern in 1 pt (3.6%). Cytogenetic studies revealed Normal karyotype in 6 pts (21.43%), complex karyotype in 6 pts (21.43%), Philadelphia chromosome positivity in 3 pts (10.71%), MLL rearrangement in 1 pt (3.57%) and other chromosomal abnormalities in 9 pts (32.14%). Cytogenetic studies failed in 2 pts (7.14%) and no data was available in 1 pt (3.57%).Induction therapy was of AML type in 5 pts (17.9%), ALL type in 8 pts (28.6%), and combination of AML and ALL type in 15 pts (53.6%), and 2 of the 3 pts with Philadelphia positivity also received imatinib (one patient was treated in the pre-Imatinib era) with induction chemotherapy. Twenty (71.43%) pts achieved complete remission (CR), 16 with one cycle and 4 with two cycles. Twelve pts went on to receive high dose chemotherapy with SCT. Stem cell source was autologous in 2 pts (16.7%), related donor in 3 pts (25%), unrelated donor in 6 pts (50%), and unrelated cord blood in 1 pt (8.3%). Eleven of 12 pts were in first CR and one was in second CR before SCT. Conditioning chemotherapy was TBI-based in 7 pts and busulfan based in 5 pts.ALL treatment induced a remission in 45%, AML therapy in 0% and 53% responded to combination therapy. EFS and OAS estimates for all 28 patients at 15 years were 29% (95% CI 13% to 48%) and 40% (95% CI 21% to 58%) respectively. Patients receiving high dose chemotherapy and SCT had significantly improved OAS of 63% (95% CI 29% to 85%) vs. 23% (95%CI 6% to 46%) for those receiving only chemotherapy (P = .019). OAS for pts with presenting WCC of <30x109 was significantly better compared to pts with presenting WCC of >60x109 (54% vs. 0%, p = .039).”Myeloid + B lymphoid” group had better OAS estimates compared to “Myeloid + T- lymphoid” group (59% vs. 29% respectively, but not statistically significant, p= 0.1135). Type of induction chemotherapy, and age at diagnosis were not statistically significant outcome predictors.Although a small sample size, this study would suggest that adult patients with BAL who achieve a CR with standard chemotherapy should be considered for high dose chemotherapy and stem cell transplantation. This modality of treatment gives them the greatest probability of long term overall survival.Sutherland: Celgene: Honoraria; Janssen : Honoraria; Novartis: Honoraria. Toze:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding.

Double-hit (DHIT) lymphoma is a heterogeneous group of non-Hodgkin lymphomas characterized by concurrent translocations involving MYCand BCL2and typified by aggressive behavior and poor prognosis with only rare long-term survivors. There is no established treatment for DHIT lymphoma. Since 2003, the British Columbia Cancer Agency (BCCA) has adopted the use of intensive chemotherapy CODOX-M/IVAC combined with rituximab (R) followed by high-dose chemotherapy and hematopoietic cell transplantation (HSCT) as definitive treatment for DHIT lymphoma. In younger patients, an ablative matched sibling donor allotransplant (AlloSCT) is preferred over an autotransplant (AutoSCT). For all patients over the age of 60 years only AutoSCT is offered. Total Body Irradiation (TBI) is used as a part of the conditioning regimen for patients younger than 60 years of age. Here we report our provincial experience with this strategy, focusing on the ability to deliver this treatment and survival outcomes.

Abstract 4132

No relevant conflicts of interest to declare.

Invasive fungal infection (IFI) is both highly prevalent and highly morbid in the allogeneic transplant (HSCT)patient population. We have previously documented an incidence of IFI in our HSCT patient cohort of 20%(2006–2007). At the time of the initial analysis, low dose amphotercin B (LDAB) (10mg/m2) was the routine prophylaxis given for the neutropenic phase post HSCT. This study was carried out to analyse whether an alteration in prophylaxis strategy for patients during the neutropenic phase post HSCT was effective in reducing the incidence of IFI in this heavily immunocompromised patient group. We also aimed to identify risk factors for IFI which would help to guide prophylactic strategies beyond the neutropenic phase.A retrospective analysis of all patients undergoing allogeneic stem cell transplant between January 2010 and June 2011 was carried out. 67 patients thus identified were reviewed and the incidence and risk factors for IFI in this group was compared to our historical control group from 2006–2007 (n=69). Patients with a prior history of IFI were excluded. EORTC criteria were used to define possible, probable or proven IFI. Diagnostic criteria guiding treatment of IFI did not change between the two study periods. Micafungin 100mg iv was the prophylaxis given to inpatients undergoing myeloablative or unrelated donor non myeloablative transplantation. For outpatient based non- myeloablative transplants, fluconazole 200 mg orally daily was the prophylaxis of choice. Prophyaxis was started on day +1 and was continued until absolute neutrophil count (ANC) was >0.5× 109/L.The overall incidence of IFI was 10/67 (15%), with 5% proven/probable and 10% possible IFI's. The median time to diagnosis of IFI was 78 days from date of transplant. This represents a decrease in incidence of IFI compared to the earlier cohort (20%). The reduction in IFI seen in our current cohort of patients who received micafungin or fluconazole prophylaxis appears to be largely attributable to a reduction in the rate of early (before day +30) IFI in the group of patients treated with iv micafungin (Table 1). Only one of the 43 patients given micafungin prophylaxis developed an IFI in the first 30 days following transplantion.Timing of IFI; median time to diagnosis of IFI was 78 days. Only two patients developed an IFI during the neutropenic phase post chemotherapy (20%), 4 patients developed IFI between days 30 and 100 and 4 patients developed an IFI after day 100. (38%, 17% and 45% in earlier cohort.Risk factors for IFI were assessed(Table 2). Of striking significance is the finding that those patients who developed steroid refractory graft versus host disease (GVHD) had an incidence of IFI of 56% (5 of 9 patients developed an IFI) compared to those patients with GVHD who did not require second line therapy of whom only 7% developed an IFI.50% (5/10) of patients who developed an IFI have died compared to 9% of the patients in the no IFI group (5/57). Mortality attributable to IFI was 30% in the IFI group.We demonstrate a reduction in early IFI in patients prophylaxed with micafungin in this small series of uniformly treated patients. Late IFI remains a problem and we have identified a subgroup of patients for whom further prophylaxis is warranted. Prophylaxis with a mold active azole should be given to all patients who develop steroid refractory GVHD given the unacceptably high incidence of IFI in this patient subset.Sutherland: Centocor Ortho Biotech research & Development: Research Funding.

Clonal evolution (CE) and variant Philadelphia (Ph) chromosomal translocations (vPh) are seen in <10% of newly diagnosed CML patients. While the vPh is thought to have no prognostic significance, CE maybe associated with an inferior outcome compared to the presence of a single standard Ph for patients treated with imatinib (IM). This study aims to evaluate the prognostic significance of vPh and clonal evolution in a cohort of CML chronic phase (CP) and accelerated phase (AP) patients treated with IM.From June 1999 to December 2008, 247 Ph+ CML CP and AP patients treated with IM (300–600 mg daily) were analyzed. Patients having had a prior allogeneic stem cell transplant were excluded. Patients were categorized into 4 groups according to karyotype at diagnosis: Group 1 (CP with CE only, n=28); Group 2 (AP, n=31); Group 3 (CP with vPh, n=20); Group 4 (CP with standard Ph, n=168). Cytogenetic response, treatment failure, event free survival (EFS) and overall survival (OS) were calculated for each group and multivariate analysis was performed to determine potential variables predictive of response and survival.Groups 1 and 2 had lower complete cytogenetic responses (CCR) to IM and higher rates of treatment failure compared to Group 4. (Table1). At a median follow up 4.2 years, Groups 1 and 2 had lower median OS and EFS compared to Groups 3 and 4 (Table1). The 5 year probabilities of OS and EFS were 79 % and 53 % (Group 1), 77 % and 73 % (Group 2), 94 % and 87 % (Group 3), and 90 % and 83 % (Group 4). (Figures 1 and 2).In multivariate analysis, the only significant factors predictive of CCR were Sokal score (p=.01), CE at diagnosis (p=.03) and dose of IM (p=.03). When the analysis was restricted to EFS and OS, the presence of CE at diagnosis (p<0.0001), prior treatment before IM (p=0.04), the dose of IM (p=0.01) and the response to IM (p<0.0001) were the factors associated with significant EFS and the presence of CE at diagnosis (p=0.004), the dose of IM (p=0.05) and the response to IM (p<0.0001) were predictive of OS. The presence of a vPh had no effect on EFS and OS.The presence of CE at diagnosis and/or features of AP in patients with CML treated with IM are associated with an inferior prognosis, but the presence of the vPh does not appear to have any prognostic significance. It remains to be determined whether the second generation TKI's can overcome the negative influence of CE on EFS and OS.No relevant conflicts of interest to declare.

Abstract 4567

No relevant conflicts of interest to declare.

AML in patients above age 60 is associated with adverse outcomes compared to younger patients. This is due to the higher incidence of adverse risk cytogenetic changes, poor performance status and end organ function that precludes patients from receiving intensive chemotherapy. Large population based studies have reported 5yr survival rates of 5–8% even in patients receiving standard ‘3+7’ induction chemotherapy. Our study looks at the effect of disease and patient characteristics on outcomes in elderly AML patients who received remission induction chemotherapy in the hope of predicting which individuals would benefit most from this treatment.Retrospective data was collected from 381 patients > age 60 who underwent conventional cytarabine and daunorubicin (7+3) induction and consolidation chemotherapy after clinical evaluation suggesting they were fit for such treatment, from Jan 1990 to Sept 2009.The follow up duration ranged from 6m–19.5 years. The data collected were age, ECOG performance status,Haematopoetic stem cell transplant comorbidity Index (HCI) (Sorror et al Blood 2005;106:2912),WBC at presentation, bone marrow blast percentage, antecedent hematologic disease (AHD), Cytogenetic risk group by MRC(UK) criteria, remission status, date of relapse, mortality and overall survival (OS). Statistical analysis was performed to determine variables affecting OS using Cox regression analysis. Multivariate Cox regression coefficients were used to generate a nomogram to predict OS based on Akaike's information criterion.The CR rates in the 3 MRC risk groups were 95%,75% and 40% respectively. The 8 week mortalities in the 3 risk groups 10%,8%and 29% respectively. The 3 month survival was 85%, 1year 50% and 5yr 16% for the patients as a whole. Multivariate analysis showed that age at diagnosis, WBC, cytogenetic risk group and AHD affect OS while sex, ECOG, HCI and BM blast count do not. Using the 4 variable significantly predicting OS a nomogram was developed. Its ability to predict OS of individual patients was evaluated using bootstrapping of a set of 200 resamples. To use the nomogram, draw a line straight upwards to the points axis to determine the number of points received for each of the 4 variables. The sum of these numbers is located on the Total Points axis, and a line is drawn downward to the survival axes to determine the likelihood of 1-, 3- or 5-year OSAML in patients > age 60 is typically associated with a poor outcome after intensive chemotherapy. However, even among this high risk group results are heterogeneous. This is illustrated in our study where the CR rate and induction mortality varied substantially across cytogenetic risk groups. In addition to the cytogenetic risk group we found age, WBC at diagnosis and the present of AHD to have prognostic value in this elderly group. However, the HCI was not predictive of survival in these AML patients > age 60 receiving standard induction and consolidation chemotherapy. The prognostic patient factors identified in multivariate analysis are easily available in newly-diagnosed AML patients, usually before decisions regarding initial therapy must be made. If confirmed in a larger prospective study, the nomogram we have developed will help clinicians predict the expected survival following intensive chemotherapy, thus helping the patient to make an informed choice regarding risk vs benefit.Sutherland: Centocor Ortho Biotech research & Development: Research Funding.

Abstract 1694

Abstract 3100

Abstract 2561

Toze: Hoffman La Roche: Consultancy, Honoraria, Research Funding; Genzyme: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria. Sutherland:Celgene: Honoraria; Orthobiotech: Honoraria.

The use of allogeneic hematopoietic stem cell transplant (alloHSCT) in the treatment of Multiple Myeloma (MM) remains controversial. Although there is hope that alloHSCT may result in a cure, relapse continues to be a significant problem. The morbidity associated with late complications of allogeneic transplantation further compounds the issues faced when addressing relapsed disease. The use of Novel Agents (NA) in this patient population has been poorly characterized. Here we present our experience of NA use in patients initially treated with alloHSCT.108 patients underwent an allografting procedure for their MM at our center between 1989 and 2009. 84 received a fully myeloablative procedure (15 received donor lymphocyte infusion). 24 received an autologous HSCT followed by a reduced intensity allogeneic procedure. 56 have relapsed with this population making up our primary cohort for analysis. 22 patients received NAs and very few patients received them prior to transplant (4/108). Endpoints examined were post relapse survival after the initial HSCT procedure (PRS), overall survival from time of initial treatment (OS) and progression free survival (PFS) measured in months (m).Of the entire cohort of 108 patients median OS was 78.6m (95% CI; 24.5–132.6). Median PFS was 23.6m (95% CI; 15.4–31.8). Of the non-relapsed patients (n = 52) the median OS was 125.9m. In this cohort 67% of the deaths occurred within 1.5 years. Of the relapsed patients (n = 56) median PFS was 18.7m (95% CI; 14.6–22.8), median PRS was 31.5m (95% CI; 17.0–46.0), and median OS was 67.0m (95% CI; 31.6–102.5). The effect of NA was examined in the cohort of relapsed patients. No significant difference was noted in PFS between those exposed to NA and those who were not exposed (19.0m (95% CI; 10.1–22.8) vs 13.7m (95% CI; 5.8–21.6); p = 0.27). Exposure to NA showed improvements in PRS (42.3m (95% CI; 7.3–77.2) vs 10.4m (95% CI; 5.2–15.7); p = 0.01, Figure 1). A trend toward superior OS was noted (71.4m (95% CI; 37.9–105.5) vs 24.6m (95% CI; 3.0–46.1); p = 0.11) although this did not reach statistical significance.Ongoing management of relapsed patients with multiple myeloma in the post alloHSCT setting remains a significant challenge. This retrospective study demonstrates that the use of NA is both safe and effective in treating relapsed disease. The predominant impact of these drugs is seen in the relapsed setting. Exposure to NA correlates with a 22m improvement in PRS. A 46m improvement in OS is noted however, likely due to the small cohort, it failed to reach statistical significance.Sutherland: Celgene: Honoraria; Orthobiotech: Honoraria. Shepherd:Celgene: Honoraria; Orthobiotech: Honoraria. Nevill:Celgene: Honoraria. Toze:Hoffman La Roche: Consultancy, Honoraria, Research Funding; Genzyme: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria.

Abstract 4580

Abstract 3465

Invasive fungal infections (IFI) are associated with significant morbidity and mortality in hematopoietic stem cell transplant (HSCT) patients. Prophylaxis of high risk patient groups has become a key strategy in managing these infections, which are characteristically difficult to pre-emptively diagnose. The benefit of newer prophylactic agents depends in part on the local incidence of IFI in a population. This study was carried out to define the incidence of IFI in a cohort of HSCT patients treated by the Leukemia/Bone Marrow Transplant Program of British Columbia, to elucidate risk factors for IFI and to assess the efficacy of our current prophylaxis strategy.Two hundred and forty-nine adult HSCT patients who underwent autologous or allogeneic transplantation between October 2006 and March 2008 were retrospectively evaluated. One hundred and eighty patients underwent high dose chemotherapy and autologous HSCT during this period. The indication for HSCT in this group was predominantly multiple myeloma (n=95; 53%) or non-Hodgkins lymphoma (n=59; 32.8%). Sixty-nine patients underwent allogeneic HSCT using a related sibling (n=46) or matched unrelated (n=23) donor. The predominant indication for allogeneic HSCT was acute leukemia/ myelodysplasia (48%), followed by non-Hodgkins lymphoma (25%) and chronic lymphocytic leukemia (12%). Patients enrolled in prophylaxis clinical trials or with previously documented IFI were excluded from analysis. Routine antifungal prophylaxis with low dose amphotericin B (10mg/m2/day) for inpatients and oral fluconazole (400mg/day) for outpatients was given during the neutropenic phase throughout the period of the study.The overall incidence of proven, probable or possible IFI was 2.2% (4/180) and 19% (13/69) in autologous and allogeneic HSCT groups, respectively. The median time to IFI in autologous HSCT recipients was 12.5 days (7-19) post transplantation. In allogeneic HSCT patients, a bimodal incidence of IFI was observed with the first peak occurring within the first 30 days of transplantation and a later peak after 100 days. Invasive aspergillosis (IA) was the predominant IFI encountered (82%); the remaining IFI were due to invasive candidiasis (IC). The incidence of IA was 1.7% (3/180) and 16% (11/69) in autologous and allogeneic HSCT patients. Mortality attributable to fungal infection was 18% (3/17) and all deaths were cases of IA occurring in the allogeneic HSCT group. Modification of antifungal prophylaxis occurred in 23% of patients. Indications for changes in prophylaxis included: initiation of empiric therapy for suspected infection (18%), change to an orally active agent to facilitate discharge from hospital (12%), nephrotoxicity (14%) or infusion reactions (2%). Patients who developed IFI were more likely to have received prolonged high-dose corticosteroid therapy (i.e. prednisone >7.5mg daily for 3 weeks or more) for graft-versus-host disease (82% in IFI vs. 24% in non-IFI, p<0.001). Patients who received alemtuzumab or fludarabine as part of the conditioning regimen were also more likely to develop IFI (23% in IFI vs. 1.3% in non-IFI, p<0.001) and (23% in IFI vs. 6% in non-IFI, p=0.005), respectively. IFI patients were more likely to have received total parenteral nutrition during the peritransplant course (47% in IFI vs. 18% non-IFI, p<0.001).Invasive fungal infections occurred in 19% of allogeneic HSCT recipients with an attributable mortality of 18%. IFI is less concerning in autologous HSCT recipients, occurring in 2% of cases. The predominant infection of concern is invasive aspergillosis in our population. Patients should receive prophylaxis during the neutropenic phase following allogeneic HSCT; those who develop graft-versus-host disease requiring prolonged steroid therapy should be particularly targeted for antifungal prophylaxis with mould-active antifungal agents. The role of T cell suppression in conditioning therapy and the influence of TPN exposure on the incidence of IFI is an area which warrants further study in defining specific risk groups for costly and potentially toxic prophylactic therapy.No relevant conflicts of interest to declare.

Relapse within 12 months of stem cell transplant is an important clinically relevant prognostic factor predicting poor outcome for patients with multiple myeloma (MM). Little is known about the use of novel agents (NA) in this setting and their impact on survival. In British Columbia autologous stem cell transplantation (ASCT) as a part of initial treatment is the standard of care for patients who are eligible. The use of NA is largely restricted to the relapsed setting thus providing a large cohort of patients to assess the impact of these drugs.We reviewed our experience with 418 patients with MM treated with ASCT diagnosed between 1985 and 2008. 307 have relapsed. Although thalidomide was available starting in 1999, the other novel agents, bortezomib and lenalidomide, were not available until after 2004, permitting division into two groups before and after Dec 2004.The cohort was separated into four groups based upon year of relapse (pre and post 2004) and remission duration post ASCT. Early relapse was defined as recurrence within 12 months (m) of ASCT. Four groups were defined: Group A, late relapse after 2004 (n=138); B, early relapse after 2004 (n=70); C, late relapse before 2004 (n=58); D, early relapse before 2004 (n=41). We examined the impact of NA exposure on post relapse survival (PRS).Median overall survival from diagnosis of myeloma of the whole cohort was 79.9 months (95% CI; 70, 89). Median PRS was 31.0m (95% CI; 25, 36). Exposure to novel agents conferred a better PRS (35.7m, 95% CI; 30, 42 vs. 9.1m, 95% CI; 4, 13; p < 0.001). Results comparing the various groups are summarized in table 1. Kaplan-Meier curves of the four groups are shown in figure 1.Post relapse survival for patients with MM treated with ASCT has improved with the introduction of novel agents. Although relapse within 12m of ASCT remains an important clinical prognostic factor predicting worse outcome, the introduction of bortezomib and lenalidomide after 2004 correlates with a 24 month improvement in post relapse survival in these patients.Connors: Roche Canada: Research Funding.