ALBERT

Description: Background Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma associated with poor outcomes. First-line treatment incorporates cytotoxic chemotherapy and rituximab, but there is no single standard of care regimen. In British Columbia (BC), between January 2003 and May 2013, R-CHOP was the preferred induction regimen. Based on results from the STIL-1 trial (Rummel et al, Lancet 2013) demonstrating improved CR rate and prolonged progression-free survival (PFS) of bendamustine and rituximab (BR) compared with R-CHOP, in June 2013, BR became the standard first-line therapy for all patients with MCL regardless of age. In both eras, fit patients generally ≤65 years of age responding to induction were eligible for high-dose BEAM and autologous stem cell transplantation (ASCT). Maintenance rituximab (MR) has been offered to responding patients post ASCT since 2004 and for transplant ineligible patients since 2012. The aim of this study was to assess the efficacy of BR as an induction regimen for MCL. Methods Patients with MCL treated with first-line BR were identified in the BC Cancer clinical and pathology databases as well as the Leukemia/BMT Program of BC transplant database. BR was initiated no later than December 2018. Treatment received was verified using the BC Cancer Provincial Pharmacy database, and clinical characteristics were verified using the BC Cancer Information System. Radiotherapy for localized disease, splenectomy, or a period of observation prior to systemic therapy were permitted. PFS and overall survival (OS) were calculated from the date of initiation of systemic therapy. In the subgroup of patients ≤65 years of age, results were compared to a historical cohort uniformly treated with R-CHOP. Baseline and treatment characteristics associated with PFS or OS (p65 years old, 9 underwent ASCT (age 66-71) and 92 did not. 63/69 patients received MR after ASCT, and 77/121 received MR after BR (without ASCT). Reasons for not receiving MR (6 after ASCT, 44 after BR) were 25 PD, 10 ASCT/BR toxicity, 7 pending, 3 patient preference, 3 early deaths, 2 physician preference. With a median follow-up of 2.4y (range 0.2 - 6.1) in living patients the 3y OS was 69.5% (95% CI 69.4-70.6) and 3y PFS 62.8% (95% CI 62.4-63.6). Baseline characteristics and outcomes were similar between patients ≤65y treated with BR vs. R-CHOP (Table 1, Figure 1A and 1B). 81/140 (58%) patients treated with R-CHOP underwent ASCT. In the subgroup of patients who underwent ASCT, outcomes calculated from the point of ASCT were not statistically different between BR vs. R-CHOP. In univariate analysis, age 〉65y, ECOG performance status 〉1, elevated LDH, blastoid/pleomorphic morphology, no ASCT, and no MR were associated with worse PFS and OS. In multivariate analysis including these variables as well as chemoimmunotherapy regimen, treatment with BR was not associated with PFS or OS. Conclusions In this population-based analysis, BR is an effective induction regimen for both transplant eligible and ineligible patients. ASCT is feasible in patients treated with BR induction. Even though BR was associated with a numerical improvement in PFS compared to R-CHOP in patients ≤65y, differences in PFS and OS were not statistically significant. Longer follow-up is necessary to fully understand the impact of BR in the frontline setting. We observed PD in 12% patients, suggesting that BR may not be an optimal induction regimen across all patients with MCL, particularly in those with aggressive or highly proliferative disease. Disclosures Villa: Roche, Abbvie, Celgene, Seattle Genetics, Lundbeck, AstraZeneca, Nanostring, Janssen, Gilead: Consultancy, Honoraria. Sehn:Morphosys: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Merck: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Janssen-Ortho: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria. Savage:BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Song:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Scott:Roche/Genentech: Research Funding; Celgene: Consultancy; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria.

Description: Abstract 3100 The advent of reduced intensity (RI) conditioning for allogeneic stem cell transplant (HSCT) has brought the question of safe application of this therapy (tx) to older patients. This is of particular importance in CLL where the median age at diagnosis (dx) is 65 yrs. This study compares outcome post RI HSCT in those aged 60 and older (older group, n=23 pts) to those less than age 60 (younger group, n=35 pts) who received RI HSCT at the Leukemia/BMT Program of BC 2001 - June 2011 (total group n=58). Forty-two of 58 (73%) were male. Racial origin was mostly white with only 2/58 (3%) Asian pts. Max stage (Rai) pre-HSCT was advanced (III + IV) in most (31/58, 53%); 13 pts (22%) had B symptoms. Characteristics of the entire group (n=58) include (med, range): interval from dx to HSCT 7.4 yrs (0.4–29); number of prior tx 4 (1–14) and % lymphocytes in pre-HSCT marrow 71 (3–98). 22% (13/58) had bulky nodes (〉5cm). Six (10%) had Richter's transformation. HSCT comorbidity index (Sorror) was 0 in 33 (57%), 1–2 in 18 (31%) and 〉= 3 in 7 pts (12%). Most received prior nucleoside analog (57/58, 99%) and rituxan (47/58, 81%) tx. Twenty-five (43%) were resistant (RES) to last tx given; 30 of 56 pts (54%) were fludarabine (flu) RES. The younger and older group were similar apart from age at dx and HSCT (med, range) which were 47 (26–57) vs 54 (36–55) yrs and 56 (42–59) vs 63 (60–68) yrs respectively. Med donor age was 46 yrs (19–76); 39 (67%) were male; 83% of female donors were parous; 27 (47%) were unrelated (UD); and 12 (21%) mismatched. Stem cells were peripheral blood. Conditioning was non-myeloablative (flu/cy) in 14 pts (24%), and reduced intensity (fludarabine/busulfan) in the remainder (44 pts, 76%). For UD HSCT campath was added to flu/bu in 19 and thymoglobulin in 8 pts. Gvhd prophylaxis was cyclosporine and methotrexate. Count recovery occurred in 97%; 2 pts did not recover (both 1 year post 2nd RI UD HSCT. Graft failure (GF) occurred in 8 pts (14%) predominantly related to campath; 1 pt died (H1N1), 1 is well with autologous recovery 3 yrs post GF and 6 of 8 required further HSCT (including 2 older pts who survive 〉 1 yr post 2nd HSCT). Acute graft vs host disease (gvhd) grades 2–4 occurred in 83% of pts and chronic gvhd in 54% and was neither more severe nor prevalent in older pts. CR post HSCT has occurred in 26 /58 pts (45%), a med (range) of +108 days (0 days -5.4 yrs). DLI was given to 11 pts (4 older pts). At median (range) follow up of 20 months (0.3–120) post HSCT and 10.1 yrs (0.7–37) post dx 44 / 58 pts (75%) survive in the whole group, including 25/35 pts (71%) younger group and 19/23 pts (83%) older group. Death in CR occurred in only 2/14(14%) deaths or 2/58 pts (3%), both of whom were younger pts. Time of death post HSCT was similar in the younger and older groups. Pre-HSCT FISH was performed in 52 /58 pts; results were abn in 47/52 pts (90%); 28/29 (97%) younger and 19/23 (83%) older group and included: del 17p in 15 pts (26%); del 11q in 15 (26%); trisomy 12 in 11 (19%); del 13q in 29 (50%) and bi-allelic del 13q in 11 (19%). Abn FISH normalized pre-HSCT in 8 /52 (15%) and post-HSCT in 18/40 pts (45%), leaving only 22/54 (40%) with currently abnormal FISH tests. Donor chimerism 〉=90% was achieved to date in 43/50 assessable pts (86%) and occurred with similar frequency in younger and older age groups. Survival analysis for the whole group demonstrated the following had a positive impact on OS (p value): achievement of donor chimerism 〉 90% (0.006); CR post HSCT (0.010) and normal FISH or clearance of previously abn FISH (0.007). Non-significant factors included FISH (Dohner ranking); 17p del; acute gvhd gr 2–4; cgvhd; and patient age. KM estimate for OS at 1, 2, and 5 years is: whole group 85%, 73%, 73%; younger 82%, 73%, 73; older 90%, 72%; 72%. There is no difference in OS for the younger vs older group (p= 0.7). In conclusion advances have now made it possible to safely and successfully perform RI HSCT for fit older pts with CLL and obtain similar outcome and overall survival to younger pts. This allows application of this potentially curative therapy to this important patient population. Disclosures: No relevant conflicts of interest to declare.

Description: Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an autosomal dominant syndrome characterized by platelet abnormalities and a predisposition to myelodysplasia (MDS) and/or acute myeloid leukemia (AML). The disorder, caused by inherited mutations in RUNX1, is uncommon with only 14 pedigrees reported. We screened 10 families with a history of more than one first degree relative with MDS/AML for inherited mutations in RUNX1. Germ- line RUNX1 mutations were identified in 5 pedigrees with a 3:2 predominance of N-terminal mutations. Several affected members had normal platelet counts or platelet function, features not previously reported in FPD/AML. The median incidence of MDS/AML among carriers of RUNX1 mutation was 35%. Individual treatments varied but included hematopoietic stem cell transplantation from siblings before recognition of the inherited leukemogenic mutation. Transplantation was associated with a high incidence of complications including early relapse, failure of engraftment, and posttransplantation lymphoproliferative disorder. Given the small size of modern families and the clinical heterogeneity of this syndrome, the diagnosis of FPD/AML could be easily overlooked and may be more prevalent than previously recognized. Therefore, it would appear prudent to screen young patients with MDS/AML for RUNX1 mutation, before consideration of sibling hematopoietic stem cell transplantation.

Description: Abstract 1968 Background: Recent advances in HSCT have resulted in improved overall and relapse-free survival and decreased incidence of serious complications. Improved survival has prompted an increased focus on enhancing HRQoL. There is an accumulating body of evidence emphasizing that physical activity (PA) may be one modifiable lifestyle factor associated with decreased negative side effects related to HSCT and improved HRQoL. We sought to summarize the available evidence related to the effects of PA participation and HRQoL in HSCT recipients. Methods: We searched electronic databases including Pubmed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and conference proceedings from American Society of Hematology and American Society of Clinical Oncology to April 1, 2012. No language or publication date limits were used. Studies were eligible for inclusion if they were randomized controlled trials (RCTs) or quasi-experimental trials with a control group comparing exercise interventions with placebo-control or standard of care in adult HSCT recipients. Exercise was defined as any form of PA that was performed on a repeated basis for a fixed time frame over a fixed time interval. Included studies were required to have a HRQoL measure as a primary (1o) or secondary (2o) outcome. Change in global HRQoL from pre to post-intervention for intervention and control groups were compared using a DerSimonian and Laird random effects model. Heterogeneity was assessed by calculating the Q- and I2 statistics. Meta-regression was performed for the following study characteristics: total number (no.) of study participants; mean age; % female; average body mass index (BMI); mean exercise duration in minutes per session; intervention length in weeks; % adherence; type of transplant (allo- or combination of allo- and auto-transplants); and whether HRQoL was a 1o or 2o outcome. Sensitivity analysis assessed the cumulative effect of studies by publication year and no. of participants. Influential analysis was conducted to determine change in pooled effect estimate by removing one study at a time. Publication bias was assessed the Begg's rank correlation and Egger's regression test and plot. Results: Of the 1606 studies originally identified, 7 studies involving 420 patients who underwent HSCT (of which 208 were assigned to exercise or PA intervention) met all inclusion criteria. One study was excluded from the final analysis as it was identified as an extreme outlier. All 6 remaining studies used the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) measurement tool thus weighted mean differences (WMD) were calculated for ease of interpretation. Participation in an exercise intervention resulted in an increase in global HRQoL with a WMD of 4.72 points (95% CI: −0.04, 9.47; P = 0.05). The proportion of variability in WMD attributed to intra-study heterogeneity was 65% (95% CI: 15%, 85%; P = 0.02) and was due primarily to variation in exercise intervention protocols and study quality. Meta-regression identified that whether HRQoL was a 1o or 2o outcome significantly affected the pooled effect estimate (P=0.02). Sensitivity analysis did not reveal any important trends. Influential analysis demonstrated that the study with the most influence when removed was Baumann A, where WMD decreased to 2.86 points (95% CI: −1.25, 8.57). There was no statistical evidence of publication bias by assessment with the Egger's regression test (coefficient for bias 2.35, 95% CI −1.90 to, 6.59, P = 0.20) and Begg's rank correlation test (Z-score 0.75 with continuity correction, P = 0.45). Conclusions: This analysis summarizes the best available evidence regarding effect of exercise participation on overall self-reported HRQoL in adult HSCT recipients. The pooled estimate, after excluding outliers, showed that exercise participation resulted in a 4.72 point increase in the global HRQoL score on the EORTC QLQ-C30 measure, which was borderline statistically significant (P =0.05). This effect estimate is similar in magnitude to pivotal meta-analyses of exercise interventions in breast cancer survivors. Substantial heterogeneity existed among included trials. Larger RCTs with a strong focus on study quality and long-term effects of exercise participation should be conducted. Disclosures: No relevant conflicts of interest to declare.

Description: Chronic lymphocytic leukemia, a disease that is not curable with standard therapy, is an attractive target for allogeneic (allo) hematopoetic stem cell transplant (HSCT) with demonstrated strong graft vs. leukemia effect. However, optimal selection of patients (pts) in order to maximize outcome and minimize toxicity is still under study. We hypothesized that patient co morbidity, as measured by the HSCT adapted Charlson co morbidity index (CCI) would have a strong effect in this group of patients with older median age. At the Leukemia/BMT Program of BC the CCI has been prospectively calculated for HSCT pts since 2006, and we performed chart review to calculate scores retrospectively for the remaining CLL allo HSCT patients in order to evaluate the impact of this factor on outcome following allo HSCT. Transplant specific data was collected prospectively and entered into an electronic database. Forty pts with CLL proceeded to allo HSCT between Jan 91 and Dec 07, with myeloablative (MA) (n=21) or non-myeloablative/reduced-intensity (NMA/RIC) (n=12/7) conditioning regimen. Median (range) number of prior therapies was 4 (1–7). Twenty-four pts were refractory to fludarabine. Donors were related in 25 cases, unrelated in 15. Median age (range) was 49 yrs (32–57) (MA) and 57 yrs (52–64) (NMA/RIC), with 3 and 13 patients greater than age 55 in the 2 groups respectively. Interval from dx to HSCT was 60 months (range 7–135) (MA) and 90 months (range 18–350) (NMA/RIC). Five yr OS is 55% for the whole group; 51% for the MA group at a median follow-up (med FU) of 7.2 yrs (range 2.8–14.6) and 62% for the NMA/RIC group with med FU of 4.2 yrs (range 0.1–6.8). OS did not differ between the 2 groups (p=0.56). Related and unrelated donors had similar 5yr OS at 60.6 vs. 47.1%, p=0.23. Cumulative incidence of non-relapse mortality at 100 days and 2 years is 10 and 32% for the whole group, 14 and 38% for the MA and 6 and 26% for the NMA/RIC groups. CCI was 0, 1, 2, and 3 or greater for 21, 5, 7, and 7 patients. OS by CCI 0–2 vs. 〉=3 was 63 vs.18% for the whole group (p=0.01), 56 vs. 0% for the MA (p=0.03), and 74 vs. 27% for the NMA/RIC groups (p=0.06). Further analyses will explore the relationship between CCI and NRM, acute and chronic graft vs. host disease, and relapse. Patient numbers in this series are insufficient to evaluate the impact of specific co morbidities. In conclusion, for patients with CLL, who are in general of older age, and who may have other therapeutic options, allo SCT is optimally performed in those with a low co morbidity score. Patients with a CCI of 3 or greater may be preferential candidates for alternate less toxic therapies.

Description: Background: ABL and AUL are associated with an unfavourable outcome for patients (pts) treated with standard-dose therapy alone. Although high-dose therapy has been used successfully in this population, the optimal management of pts with ABL/AUL remains unclear. Methods: A retrospective review was performed involving 24 adult pts with ABL or AUL who were treated in Vancouver between 1984 and 2006. Kaplan-Meier estimates were utilized for event-free survival (EFS) and overall survival (OAS) and a multivariate analysis was performed to determine factors predictive of outcome. Characteristics: Utilizing the WHO criteria, 18 pts had ABL and 6 pts had AUL. There were 17 males and 7 females with a median age of 37 (range 22–75) years. Median white cell count (WCC) at presentation was 10.1 × 109(range: 0.9–196 × 109)/L. Seven pts had poor-risk karyotypes (3 pts complex, 3 pts with t(9,22), 2 pts with11q23 rearrangement, and 1 pt with monosomy 7),12 pts had standard-risk karyotypes, and 5 pts had an unknown karyotype. Induction chemotherapy consisted of Cytosine arabinoside (3–6/m2/day), Daunorubicin, Vincristine and Prednisone with one pt with t(9,22) also having received Imatinib Mesylate. Thirteen pts went on to receive high-dose therapy and SCT. Stem cell source was autologous in 3 pts (all with AUL) or a related (6 pts) or an unrelated donor (4 pts). Eight of 10 pts were in complete remission at the time of SCT, one was in relapse and one had primary refractory ABL. Conditioning was TBI-based in 10 pts and Busulfan-based in 3 pts. Results: EFS and OAS estimates for all 24 patients at 3 years were 25% (95% CI 13%–50%) and 32% (95% CI 17%–58%), respectively. The non-relapse mortality (NRM) for the whole group at 3 years was 43% (95%CI 15%–61%). On multivariate analysis, when compared to pts receiving only standard-dose chemotherapy, pts who underwent high-dose therapy had significantly improved EFS [39% (95% CI 19%–77%) vs. 9% (95% CI 1%–59%), p=.03] and OAS [46% (95% CI 26%–83%) vs.14% (95% CI 3–74%), p=0.01], respectively. Age, WCC at presentation and cytogenetic risk group were not found to significantly influence outcome. Conclusion: Although patient numbers are limited, this experience would suggest that patients with ABL/AUL who achieve complete remission with standard chemotherapy should be considered for high-dose therapy and stem cell transplantation. This approach provides them with the greatest probability of long-term event- free and overall survival.

Description: Acute promyelocytic leukemia (APL) has become one of the more readily treatable subtypes of acute myeloid leukemia on the basis of its particular sensitivity to anthracyclines and the introduction of the differentiating agent all-trans retinoic acid (ATRA). Unfortunately some patients will ultimately relapse after achievement of complete remission. A PETHEMA and GIMEMA (PETH/GIM) cooperative group joint study sought to identify risk factors associated with relapse and developed a predictive model based on white cell count (WCC) and platelet count (Plt) at diagnosis. This model for relapse free survival was capable of segregating patients into low risk (WCC 〈 10 x 109/L / Plt 〉 40 x 109/L), intermediate risk (WCC 〈 10 x 109/L / Plt 〈 40 x 109/L), and high risk (WCC 〉 10 x 109/L). A subsequent follow up study demonstrated improved outcomes for intermediate and high risk group patients treated with an anthracycline and ATRA based risk adapted strategy. We reviewed 60 cases of adult de novo APL treated at Vancouver General Hospital from August 1995 to December 2003. Thirty five females (58%) and 25 males (42%) were treated with a standard induction and consolidation protocol consisting of 3 cycles of Daunorubicin (60 mg/m2 OD for 3 days), Cytosine arabinoside (100 mg/m2 BID for 7 days), and ATRA (45 mg/m2/day until complete remission or a maximum of 60 days). In 2000 maintenance therapy was introduced and ATRA and/or varying doses of Methotrexate and 6-Mercaptopurine were then instituted for up to 2 years duration. At the completion of induction chemotherapy complete morphological and cytogenetic remission was achieved in 55/60 patients (92%) with 4 induction failures and only 1 death during induction treatment. Subsequently during and after consolidation and maintenance therapy at a median follow up of 34 months there were a total of 10 episodes of relapse (18%) in these 55 patients. When the 55 patients in complete remission were stratified at diagnosis by the PETH/GIM risk group there were 18 low risk patients (33%), 26 intermediate risk patients (47%), and 11 high risk patients (20%). The number of relapses was 6 in the low risk group (33%), 4 in the intermediate risk group (15%) and no relapses were identified in the high risk group. In our experience the predictive model for relapse free survival developed by the PETH/GIM cooperative group does not identify those at most likelihood for subsequent relapse after achieving an initial complete remission. The greatest number of relapse was seen in the low risk group with no relapses in the high risk group. These variations may be explained in part by the different chemotherapy treatment protocols with variable maintenance therapy. Future investigation will focus on the prognostic role of immunophenotype, additional cytogenetic abnormalities and molecular isoforms in determining outcome in APL.

Description: A substantial proportion of lymphoid malignancy cannot be cured with conventional therapy or autografting, and a matched family donor is available for less than 1/3 of patients (pts) who may benefit from an allograft. Alternate donors (AD) were therefore utilized with curative intent for 87 pts with acute or chronic lymphoid malignancy at the Leukemia/BMT Program of BC between 1983 and 2002. Long-term results for these pts who received stem cells from unrelated donors (UD) (n=73) or mismatched related donors (MMRD) (n=14) were analyzed. UDs were HLA matched in 58 cases for HLA A, B and DR, and mismatched at 1 or 2/6 loci in 15 pts. Related donors were mismatched at 1/6 (n=13) or 2/6 loci (n=1). Diagnoses included ALL in 37 (n=12 Ph+); NHL in 28 ( n=1 Burkitt’s; n=15 aggressive; n=12 indolent); CLL in 3, PLL in 1 and myeloma in 18 pts. Transplant occurred a median (med) of 10 months (range 1.6 mos-14.7 yrs) post diagnosis at a med age of 36 years (range 12–53). The majority (n=57, 66%) were not in CR at the time of transplant; 53 (61%) were male. GVHD prophylaxis included cyclosporine + methotrexate in 72, T-cell depletion in 11, and other in 2 pts. Conditioning was TBI based in the majority (n=80, 92%), and busulfan based in 7 pts (8%). Most (n=83, 95%) received marrow (m) only; 2 received peripheral blood (pb) and 2 pb+m. The med (range) nucleated cell count was 2.6 (0.2–15)x108 CD 34 cells/kg; graft failure was seen in 5 cases (6%). Acute (A) graft-versus-host disease (GVHD) grade 0/1, 2, 3 and 4, (n= %), was seen in 24 (28%); 24 (28%); 19 (22%) and 19 (22%) pts. The majority (n=41/56, 73%) who survived past day 100 developped chronic (C) GVHD. Thirty pts (35%) are currently alive, and 57 (65%) deceased a median of 96 days (range 12 days-4.2 years) post transplant. Death from relapse (n=19) occurred at a med of 1 year (range 17 days-4 years), and from transplant related causes (n=38) at a med of 71 days (range 12 days-17 months). Overall survival (OS) is 32% (95% CI 23–43%) at a med follow-up of 6 years (range 1–15 years); the curve is flat after 50 mos, and 17/30 survivors are out more than 5 years. Cumulative incidence estimates are as follows: acute GVHD (gr 2–4) 72%; (gr 3–4) 44%; chronic GVHD 73%; relapse 27%; non-relapse mortality (NRM) 44%. In univariate analysis AGVHD (3–4) impacted negatively on OS, event-free survival (EFS) and NRM. Relapse risk was higher in pts receiving TCD stem cells. Development of CGHVD was protective against relapse (p=0.03, relative risk = 0.37). In conclusion, one-third of pts with otherwise incurable lymphoid malignancy have achieved long-term disease-free survival using alternate donor stem cell transplant. Strategies to decrease transplant-related mortality are needed. Control of underlying disease remains imperfect, but not unacceptable with 27% long-term risk of disease recurrence. No relapse has occurred after 50 mos, with a plateau seen in the risk curve after 5 years suggesting cure even in pts with ALL or MM. Interestingly, a graft-vs-malignancy effect can still be demonstrated in this population with lymphoid malignancy and alternative donors, with decreased relapse risk seen in pts developing CGVHD.

Description: Background: Autologous stem cell transplant (ASCT) is the standard treatment for relapsed aggressive diffuse large B-cell lymphoma. Studies are conflicting as to whether ASCT has comparable salvage rates in peripheral T-cell lymphoma (PTCL). Emerging evidence suggests that a graft-versus-lymphoma effect may exist in PTCL. Thus, allogeneic stem cell transplant (allo-SCT) may be a favoured approach for relapsed PTCL patients. Methods: The British Columbia Leukaemia/BMT database was reviewed to identify all PTCL patients who have undergone allo-SCT for relapsed/refractory or high risk PTCL. Twenty patients (13M, 7F) with PTCL received an allo-SCT between November 1990 and May 2007. Median age at transplant was 46.5 years (range 16–64 years). Lymphoma subtypes were PTCL-unspecified (n=7), anaplastic large cell (n=4), hepato-splenic γδ (n=4), angio-immunoblastic (n=3), enteropathy-type (n=1) and nasal-type natural killer (n=1). Seventy percent of the patients presented at diagnosis with two or three risk factors from the age-adjusted International Prognostic Index. The disease status at the time of transplant was: First complete remission (n=4; all 4 had hepatosplenic γδ PTCL); second or greater complete remission (n=6); first partial remission (n=1); first chemosensitive relapse (n=4); untested relapse (n=3); induction failure (n=2). Sixteen patients had matched sibling donors and 4 had unrelated donors (2 patients had mismatched donors). Sixteen patients received radiation-based conditioning regimens. Two patients received reduced-intensity conditioning regimens. Results: At the time of analysis, 5 patients have died. Three patients died within fifty days of transplant with treatment-related complications (2 acute graft-versus-host disease (GVHD), 1 pulmonary hemorrhage), 1 died of chronic GVHD and 1 died of high-grade sarcoma. Non-relapse mortality was 19% at 2 years. Median follow-up of surviving patients was 21 months (range, 1 to 163 months). Of the remaining 15 patients alive at the time of analysis, 3 had relapsed lymphoma and 12 remain in remission. Seven patients (35%) had grade 2 acute GVHD or greater. Thirteen patients (65%) had chronic GVHD (3 limited, 10 extensive). Univariate analysis was performed to determine the influence of gender, age, previous number of lines of therapy, acute GVHD and chronic GVHD. None of these factors were found to be of prognostic significance. Estimated 2-year event-free and overall survival at was 49% [95% CI: 28–83%] and 77% [95% CI: 59–100%], respectively. Risk of relapse at 2 years was 40% (95% CI: 3–63%). Conclusions: Allo SCT is a feasible option with encouraging results for patients with relapsed PTCL and select individuals with high-risk histologic subtypes.

Description: Patients (pts) with AML undergoing curative intent chemotherapy (CTX) are highly susceptible for septicemia due to profound and prolonged neutropenia, in conjunction with damage to the gastrointestinal mucosa, and the use of vascular access devices. Despite aggressive empiric antimicrobial therapy, and the use of prophylactic antibiotics, septicemia remains a major cause of morbidity in this group. Over the past decade the spectrum of pathogens that cause infections in neutropenic pts has changed, with gram+ve microorganisms replacing gram-ve bacilli. In order to identify the incidence, and cause of septicemia and the resistance pattern of bacteria in AML pts treated with curative intent CTX in the Leukemia/BMT program of BC, all positive blood cultures collected between Feb, 1999 and Feb, 2004 were evaluated retrospectively. 623 separate CTX cycles administered to 295 patients were reviewed (m=157, f=138). Median age at diagnosis was 52y (17–76). CTX regimen were classified as 7+3 or similar (conventional dose cytarabine + anthracycline) (group 1), or as high dose cytarabine containing regimen (with or without anthracycline) (group 2). 328 cycles were given as induction intend-CTX, while 295 where given as consolidation. 426 cycles were spend entirely as inpatients (IP) (from administration of CTX to ANC〉0.5); 40 cycles were spend as early discharge (ED) (from CTX administration to discharge as outpatient prior to d+15 or ANC〉0.5); 157 cycles were spend entirely as outpatients (OP). 126 episodes of septicemia were recorded in 623 cycles of CTX (20%), of which 21 episodes yielded more than 1 identified organism. Percent occurrence of septicemia stratified by CTX protocol indicated 17% (57/332) for group 1, and 24% (69/291) for group 2 (p