Yasser Mourad

Despite improvements in therapy, approximately 5% of patients who undergo autologous stem cell transplantation (ASCT) experience early mortality (EM), death within 1 year of transplant (EM post-ASCT). Such patients tend to have few comorbidities suggesting their EM is owing to aggressive underlying disease. We sought to characterize this ultra-high risk population through a retrospective review of patients with newly diagnosed multiple myeloma (MM) treated with first-line ASCT. Patients who died within 1 year of ASCT were matched for age, sex, and year of transplant in a 1:2 fashion with a control group. Of 962 transplants performed between January 1, 2007, and May 1, 2019, 41 patients (4.3%) died within 1 year of ASCT from MM-related causes. In a multivariate analysis, anemia, hypercalcemia, high-risk cytogenetics, and elevated lactate dehydrogenase were associated with EM post-ASCT. Forty patients (97.6%) received at least 1 novel agent. Most patients with EM post-ASCT received second-line chemotherapy (80.5%), although survival from initiation of second-line chemotherapy was only 2.1 months. The primary reason for not receiving second-line therapy was rapid relapse. Clinical parameters reflecting disease burden, as well as high-risk cytogenetics, are associated with EM post-ASCT. These patients have a dismal overall survival despite significant advances in treatment of patients with relapsed or refractory myeloma. Further study of these ultra-high risk patients is required to improve disease management and may give further insights into the biology of relapse and resistance in myeloma.

Introduction In 2013, bendamustine/rituximab (BR) replaced RCHOP as standard first line treatment for both transplant eligible and ineligible MCL patients (pts) in BC. Retrospective cohort studies report that bendamustine has no adverse effect on peripheral blood stem cell (SC) mobilization but this is discordant with local experience. We sought to compare rates of failed SC collection in MCL pts planned for high dose chemotherapy and autologous stem cell transplant (ASCT) after BR or RCHOP and identify risk factors for failed SC mobilization and collection. Methods We identified all pts with MCL in BC treated with BR or RCHOP as first line therapy who underwent SC mobilization from Jan. 1 2003-Dec. 31 2017 using the Leukemia/Bone Marrow Transplant Program of BC and Apheresis Database Standard mobilization was with G-CSF alone (G) until difficulties with SC collection were noted after BR. Different mobilization strategies were then used, including delaying SC collection 2-3 mos afte...

Introduction: MM remains incurable but therapeutic advances has resulted in improved overall survival (OS) particularly for younger pts who are eligible for ASCT. Regardless OS improvements have been heterogeneous and it is well known that relapse within one year of ASCT is an independent negative prognostic factor. A particularly worse subgroup is pts who relapse and die of MM within a year of ASCT. There is limited data describing this subgroup of pts, the risk factors associated with their early relapse post ASCT and characteristics at relapse. Objective: Describe patient and disease related characteristics among MM pts who underwent ASCT and died of relapsed MM within the first year post ASCT in the era of novel agents. Methods: Pts were identified from the Leukemia/BMT Program of B.C. database, underwent ASCT between January 1st 2007 and July 31st 2016 and died of MM related causes within 365 days post ASCT. During this time period bortezomib (BORT) and lenalidomide (LEN) were ...

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 (So...

1694 Background: 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. Patients and methods: 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 (E...

T-cell acute lymphoblastic leukemia (T-ALL) is a rare disease accounting for approximately 20–25% of adult cases of ALL. The outcome of adult T-ALL has improved in the past decades, but relapse remains the major cause of treatment failure. Few studies have reported on the long-term outcome of adults with T-ALL. We retrospectively reviewed the charts of 39 adult patients (pts) diagnosed with T-ALL and treated at our center between August 1986 and April 2004. Characteristics: Male/female ratio was 3.3/1. Median age was 28.4 years (16.8–73.2). ECOG PS: 0/1(n=27), ≥ 2 (n=12). Median WBC at diagnosis was 12.2 (0.9–445), Platelets 60.7 (6–270), LDH…

4580 Background: 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. Patients: 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...

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. Methods: All pts >=18 years of age diagnosed with BL from Jan. 1, 2001-Dec. 31, 2015 and initiated on CODOX-M/IVAC +/- R were identified through the Leukemia/BMT Program of BC database and cross-compared with the BC Cancer Agency Lymphoid Cancer clinical and pathology databases. The risk-adapt...

Background: Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of non-Hodgkin lymphomas (NHLs) that accounts for approximately 10% of all aggressive NHLs in Western countries. The optimal management remains unclear, however, given the poor outcome, allogeneic transplant (allo-SCT) has been integrated into the front-line treatment for some rare extranodal subtypes as well in relapsed/refractory setting. We report our provincial experience of the outcome of patients with PTCL who have undergone allo-SCT at the British Columbia Cancer Agency (BCCA). Methods: The Leukemia/BMT Program of British Columbia database and the BCCA Lymphoid Cancer Database were searched to identify all patients diagnosed with PTCL who have undergone allo-SCT between November 1990 and January 2016. Overall survival and relapse free survival were estimated using the Kaplan-Meier method. Results: We identified 36 cases of PTCL patients who have undergone allogeneic transplant from a median time...

Introduction In recent decades, overall survival rates for children with acute lymphoblastic leukemia (ALL) have improved dramatically. Unfortunately, older patients have not experienced the same benefit. Recent years have seen investigation into the use of pediatric protocols for younger adults with ALL. Increased toxicity has often limited use to patients 40 years or younger. The Leukemia/Bone Marrow Transplant Program of BC is the referral center for adults with ALL in British Columbia. Approximately 20 patients are newly diagnosed with ALL each year. Until 2008, an adult protocol (known as ALL 89-1) was used in patients over 18 years. Since 2008, pediatric-based chemotherapy has been offered to patients 40 years or younger. We analyzed whether this change altered complete remission (CR), relapse and survival rates. We assessed whether the more intense protocol increased toxicity. Methods A retrospective analysis was performed on patients treated for ALL on a pediatric-based prot...

Optimal post-remission therapy (PRT) for intermediate risk acute myeloid leukemia remains an area of ongoing research. We aimed to retrospectively compare outcomes following autologous stem cell transplantation (autoSCT) with allogeneic SCT (alloSCT) and consolidation chemotherapy (CMT) in patients with intermediate-risk karyotype AML in first complete remission. We compared overall survival (OS) and leukemia-free survival (LFS) using propensity score (PS)-adjusted analysis of patients receiving PRT with autoSCT, matched sibling (MSD) alloSCT, unrelated/mismatch (UD/MM) alloSCT, and CMT. We included patients diagnosed between 1984 and 2003 (period of autoSCT at our center) in CR1 following induction CMT and received at least 2 consolidative cycles. We identified 190 patients (62 MSD-alloSCT, 18 UD/MM-alloSCT, 30 autoSCT, and 80 CMT). Baseline characteristics were used for PS calculation and were well-balanced after weight adjustment. The median follow-up for patients surviving beyon...

The natural history of patients with myelodysplastic syndromes (MDS) is variable. The Revised International Prognostic Score (IPSS-R) is commonly used in practice to predict outcomes in patients with MDS at both diagnosis and before hematopoietic stem cell transplantation (HSCT). However, the effect of change in the IPSS-R before allogeneic HSCT with chemotherapy or hypomethylating agents on post-transplantation outcomes is currently unknown. We assessed whether improvement in IPSS-R prognostic score pre-HSCT would result in improvement in clinical outcomes post-HSCT. Secondary goals included studying the effect of prognostic factors on post-transplantation survival. All patients with MDS who underwent allogeneic HSCT at the Leukemia/BMT Program of British Columbia between February 1997 and April 2013 were included. Pertinent information was reviewed from the program database. IPSS-R was calculated based on data from the time of MDS diagnosis and before HSCT. Outcomes of patients wh...

We investigated the utility of a pediatric-inspired protocol in adults aged 18-40 years with standard-risk BCR-ABL negative acute lymphoblastic leukemia (ALL). Retrospective outcomes of 25 patients treated with a pediatric protocol between 2008 and 2014 were compared with 22 similarly aged patients treated with an adult protocol between 2003 and 2008. Twenty-five (100%) and 19 (86%) patients achieved complete remission, respectively. At median follow-up of 36.8 months, 3-year event-free survival was increased in patients on the pediatric protocol at 80% versus 45% (p = .019). There was a trend toward improved overall survival at 80% versus 59% (p = .12). Treatment-related toxicity was not increased despite the increased treatment intensity. Patients with BCR and/or ABL copy number variation demonstrated comparatively poorer outcomes in both cohorts. In our experience with this cohort of patients, pediatric-based protocols are safe and effective, justifying their use in younger adult...

The treatment of multiple myeloma (MM) has changed with the advent of thalidomide, bortezomib, and lenalidomide, the so-called novel agents (NAs). Given the complexity of MM therapy in the NA era we pursued a population based study to assess for improvements in survival as well as to characterize the relevance of early relapse (within 12 months) and the International Staging System in this clinical setting. We reviewed our experience with 460 patients with MM treated with autologous stem cell transplant (ASCT) between 1988 and 2008, of whom 306 had relapsed. The cohort was divided into two groups based upon relapse pre-2004 and relapse during/after 2004 (2004+), which correlated to availability of bortezomib and lenalidomide. Improvements in both overall survival (OS) (median 32.0 months vs. 71.8 months; p < 0.001) and post-relapse survival (PRS) (median 15.2 months vs. 42.8 months; p < 0.001) correlated with the NA era. Exposure to NAs conferred a better PRS (median 35.7 months vs. 9.1 months; p < 0.001). Although all patients had improvements in survival, those who relapsed late continued to do better. Lastly, in the NA era, the ISS remains an important prognostic tool in relapse, but only in the late relapsing cohort.

Treatment of Burkitt lymphoma (BL) with intensive, multi-agent chemotherapy with aggressive central nervous system (CNS) prophylaxis results in high cure rates, although no regimen is standard of care. We examined population-based survival outcomes of adults with BL treated with a modified combination of cyclophosphamide, vincristine, doxorubicin, prednisone and systemic high-dose methotrexate (MTX) (CODOX-M) with IVAC (ifosfamide, mesna, etoposide, cytarabine and intrathecal MTX) (CODOX-M/IVAC) ± rituximab over a 15-year period in British Columbia. For the 81 patients identified (including 8 with CNS involvement and 18 with human immunodeficiency virus-associated BL), 5-year progression-free survival (PFS) and overall survival (OS) were 75% [95% confidence interval (CI): 63-83%] and 77% (95% CI: 66-85%), respectively, with no treatment-related deaths. Those who completed the regimen per protocol (n = 38) had significantly improved 5-year PFS 86% (P = 0·04) and OS 92% (P = 0·008), a...

The aim of this study is to evaluate the activity and toxicity of the combination docetaxel and irinotecan as first-line therapy for advanced non-small-cell lung cancer (NSCLC). Twenty-two chemotherapy-naive patients with stage IIIB with pleural effusion or stage IV NSCLC received irinotecan 50 mg/m2 on days 1, 8, and 15, and docetaxel 50 mg/m2 on day 2, every 28 days until disease progression. Median follow-up was 10 months (range: 2-28 months). The overall response rate was 36.4% (8/22 patients; 95% confidence interval: 16.8-56.0), with no complete responses. Median time to disease progression was 5 months (range: 1-24 months) and median overall survival was 10 months (range: 2-28). Grade 3-4 diarrhea was observed in 2 patients (9.1%). Grade 3-4 neutropenia occurred in 2 patients (9.1%): 1 episode of febrile neutropenia in one patient, and 1 death due to neutropenic sepsis in another patient. One patient received transfusion for grade 4 anemia. Irinotecan showed a moderate respons...

ABSTRACT Thymomas usually consist of mostly benign histology, yet their malignant potential and distant metastasis remains unpredictable. Extrathoracic distant metastasis of malignant thymomas to the peritoneum are rare and only two cases are noted in the literature. We report a third case of diffuse intraperitoneal metastasis from an epithelial cell-based thymoma of the mediastinum. Metastasis to the peritoneum occurred 312 years after the initial diagnosis. Our case is noted for its aggressive behavior and relatively short interval of distant metastasis to the peritoneum despite four different chemotherapeutic regimens and radiation therapy.

Background: Allogeneic hematopoietic cell transplantation (HCT) is an important treatment for adults with acute lymphoblastic leukemia (ALL). The combination of cyclophosphamide with total body irradiation (TBI) at doses of 1200 to 1500 cGy (Cy/TBI1200) has been used in most prospective trials of HCT in ALL. However, TBI is associated with significant short and long term toxicities. Although Cy/TBI/1200 is the standard of care at most Canadian transplant centers one center instead prefers a conditioning regimen including fludarabine, busulfan, and low dose TBI (400 cGy) (Flu/Bu/TBI400) (Daly et al. BBMT 2012). We sought to compare the outcomes of HCT for adults with ALL who routinely received either Cy/TBI1200 or Flu/Bu/TBI400 as their conditioning regimen with the hypothesis that the regimens will result in similar outcomes. Conditioning regimen was highly correlated with transplant center, minimizing any selection bias in which clinicians might choose a regimen perceived to be of ...

Patient YS is a 61-year-old Caucasian woman with β-thal intermedia [Hb pattern: AFA 2 , genotype IVS-I-6 (T→C)/IVS-I-6 (T→C)]. She had never been transfusion-dependent, but was transfused during her first and second pregnancies at the ages of 18 and 23, and during surgery ( ...