Michael Crump

The Princess Margaret Hospital, Toronto, Ontario, Canada

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Publications (180)1100.5 Total impact

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    ABSTRACT: ABSTRACT Rituximab is a monoclonal anti-CD20 antibody that is standard of care for the treatment of B-cell non-Hodgkin lymphoma (NHL). The purpose of this study was to quantify the incidence of rituximab-related interstitial pneumonitis (IP) in NHL patients receiving immunochemotherapy. All patients with NHL who received CHOP, CVP, R-CHOP, or R-CVP in Princess Margaret Hospital between June 1998 and August 2009 were retrospectively reviewed. We compared cohorts of patients who did and did not receive rituximab and documented the incidence of IP during and/or post-treatment. 560 patients are included in this analysis. The rate of IP in the entire cohort was 2.9% (16/560) with a trend towards a higher rate in the R group [3.95% vs. 1.3%, (OR 3.1, 0.84-17.27, p=0.074)]. Baseline pulmonary CT abnormalities in lymphoma patients are relatively common. The addition of rituximab to chemotherapy does not significantly increase the risk of symptomatic chemotherapy-related IP.
    Leukemia & lymphoma. 10/2014;
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    ABSTRACT: Acute myeloid leukaemia (AML) patients with hyperleucocytosis have higher early mortality, lower complete remission (CR) and overall survival (OS). Whether different pre-induction leucoreduction strategies can improve outcome is unknown. A single centre retrospective cohort study was conducted on AML patients with a white blood cell count (WBC) >100 × 10(9) /l between 1987 and 1997, and on all AML patients between 1998 and 2006, to determine (a) the effect of four different leucoreductive strategies (leukapheresis, hydroxycarbamide, leukapheresis and hydroxycarbamide or no pre-induction leucoreduction) on early (day 28) mortality, CR, and OS; and (b) whether a high presenting WBC remains a negative predictor of OS in patients surviving induction (first 28 d). In the 1998-2006 cohort (n = 702), higher WBC was associated with higher early mortality and lower OS but its effects were greatly diminished in patients who survived the first 28 d (Hazard Ratio 1·094 vs. 1·002). A WBC of 34·1 × 10(9) /l had the highest sensitivity (75·6%) and specificity (67·4%) for early mortality. None of the four leucoreduction strategies differed significantly in early mortality, CR, or OS in patients with WBC>100 × 10(9) /l (n = 166). The number of leucostatic signs was a significant predictor of early mortality (P < 0·0001) and OS (P = 0·0007). The results suggest that AML patients with hyperleucocytosis should be induced, if eligible, without pre-induction leucoreduction.
    British Journal of Haematology 10/2014; · 4.94 Impact Factor
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    ABSTRACT: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 09/2014;
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    ABSTRACT: Current treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.
    BMC Cancer 08/2014; 14(1):586. · 3.33 Impact Factor
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    ABSTRACT: Abstract Purpose Extranodal natural killer T-cell lymphoma (ENKTL) nasal type is a rare form of non-Hodgkin lymphoma that is more commonly seen in Asia and Latin America than in North America or Europe. The purpose of this study was to determine the treatment outcomes with a combined modality approach and if treatment outcomes varied according to ethnicity in patients with ENKTL, nasal type in Toronto, Canada. Methods Patients presenting with ENKTL, nasal type, between 1994 and 2011 were retrospectively reviewed. Patient characteristics, including the patient's ethnic origin, treatment details, and outcomes were recorded and analyzed for significant differences between Asian and Caucasian patients. Results A total of 34 patients were identified - 16 Asian, 16 Caucasian, one Aboriginal and one Hispanic. All patients had nasal cavity involvement. The majority had localized disease: stage I (n=22), stage II (n=6); and stage IV in 6 patients. Combined radiotherapy and chemotherapy was intended for 32 of the 34 patients, with two receiving radiotherapy alone. Median RT dose was 45 Gy (range: 35-50.4 Gy). Response to initial treatment was observed in 44% of patients. Two-year disease free survival was 17.8% (Asian patients: 18.8%, Caucasians: 20%, p=0.82), and overall survival 39.2% (Asian patients: 30%, Caucasians: 42%, p=0.52). Conclusions There were no significant differences in clinical outcomes in terms of patient ethnicity. A combined modality approach (with CHOP chemotherapy administered initially) is of limited effectiveness. We have now adopted the use of radiation therapy as the initial treatment approach, followed by multiagent chemotherapy.
    Leukemia & lymphoma 03/2014; · 2.61 Impact Factor
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    ABSTRACT: The role of body mass index (BMI) in survival outcomes is controversial among lymphoma patients. We evaluated the association between BMI at study entry and failure-free survival (FFS) and overall survival (OS) in three phase III clinical trials, among patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin's lymphoma (HL). A total of 537, 730 and 282 patients with DLBCL, HL and FL were included in the analysis. Baseline patient and clinical characteristics, treatment received and clinical outcomes were compared across BMI categories. Among patients with DLBCL, HL and FL, the median age was 70, 33 and 56; 29%, 29% and 37% were obese and 38%, 27% and 37% were overweight, respectively. Age was significantly different among BMI groups in all three studies. Higher BMI groups tended to have more favorable prognosis factors at study entry among DLBCL and HL patients. BMI was not associated with clinical outcome with P-values of 0.89, 0.30 and 0.40 for FFS, and 0.64, 0.67 and 0.09 for OS, for patients with DLBCL, HL and FL, respectively. The association remains non-significant after adjusting for other clinical factors in the Cox model. A subset analysis of males with DLBCL treated on R-CHOP revealed no differences in FFS (P = 0.48) or OS (P = 0.58). BMI was not significantly associated with clinical outcomes among patients with DLBCL, HD or FL, in three prospective phase III clinical trials. The findings contradict some previous reports of similar investigations. Further work is required to understand the observed discrepancies.
    Annals of Oncology 03/2014; 25(3):669-74. · 7.38 Impact Factor
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    ABSTRACT: ABSTRACT Follicular lymphoma (FL) is characterized by initial response to treatment with inevitable relapse. We evaluated chemoimmunotherapy resistance (CIR resistance) including transformation. We identified patients who received rituximab combination therapy for symptomatic FL. CIR resistance was defined as disease progression during rituximab-based chemoimmunotherapy, rituximab maintenance or within 6 months of treatment completion. Our primary outcome was time to early progression (CIR resistance). Between July 2006 and April 2010, 132 patients met inclusion criteria and 22 (16.7%) demonstrated CIR resistance with median follow-up of 33 months. High-risk FLIPI score was predictive of CIR resistance (HR 2.43; 95% CI, 1.4 to 4.1; P = 0.001). Overall, 8 patients (36.3%) transformed (biopsy-proven) with no transformation in the chemoimmunotherapy responder group. Median overall survival in the CIR resistant group was 47 months. Patients with CIR resistance had high rates of histologic transformation and shorter survival with poor response to next therapy.
    Leukemia & lymphoma 01/2014; · 2.61 Impact Factor
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    ABSTRACT: Background The role of allogeneic (ALLO) and autologous (AUTO) stem cell transplantation in the management of patients with transformed indolent non-follicular non-Hodgkin lymphoma is unknown. Methods This is a multicenter, retrospective cohort study of patients with biopsy-proven indolent B-cell non-follicular non-Hodgkin lymphoma, and simultaneous or subsequent biopsy-proven aggressive histology transformation who were treated with ALLO or AUTO between 1996-2013. All patients received myeloablative conditioning regimens. Outcomes were compared to a cohort of 246 patients with transformed follicular lymphoma who also underwent ALLO (n=47) or AUTO (n=199) across the same institutions and timeframe. Results Thirty-four patients were identified with the following underlying indolent histologies: 15 (44%) marginal zone lymphoma, 11 (32%) chronic lymphocytic leukemia, 6 (18%) small lymphocytic lymphoma, and 2 (6%) lymphoplasmacytic lymphoma. Patients received various anthracycline or platinum-containing chemotherapy regimens for transformation, incorporating rituximab in 25 (74%). Twelve (35%) subsequently underwent ALLO, while 33 (65%) underwent AUTO. The 3-year OS after transplantation was 67% (ALLO 54%, AUTO 74%), and 3-year PFS was 49% (ALLO 40%, AUTO 54%). The 3-year non-relapse mortality was 14% (ALLO 15%, AUTO 7%). Transplant-related mortality at 100 days was ALLO 17% and AUTO 0%. Adjusted for type of stem cell transplantation, 3-year OS, PFS, and NRM were similar to those of patients with transformed follicular lymphoma receiving ALLO and AUTO (p=0.38, p=0.69, p=0.54 respectively). Conclusions ALLO and AUTO may be reasonable treatments for selected patients with transformed non-follicular indolent lymphoma, although medium-term outcomes and toxicity appear to be more favorable with AUTO.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 01/2014;
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    ABSTRACT: Treatment options for patients with nonbulky stage IA-IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques. Using German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses. With median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44). In patients with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects. The trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 - NCT00264953, HD.6 - NCT00002561.
    Annals of Oncology 10/2013; · 7.38 Impact Factor
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    ABSTRACT: PURPOSEMantle-cell lymphoma (MCL) has a variable natural history but is incurable with current therapies. MicroRNAs (miRs) are useful in prognostic assessment of cancer. We determined an miR signature defining aggressiveness in B-cell non-Hodgkin lymphomas (NHL) and assessed whether this signature aids in MCL prognosis. METHODS We assessed miR expression in a training set of 43 NHL cases. The miR signature was validated in 44 additional cases and examined on a training set of 119 MCL cases from four institutions in Canada. miRs significantly associated with overall survival were examined in an independent cohort of 114 MCL cases to determine association with patient outcome. miR expression was combined with current clinical prognostic factors to develop an enhanced prognostic model in patients with MCL.ResultsFourteen miRs were differentially expressed between aggressive and indolent NHL; 11 of 14 were validated in an independent set of NHL (excluding MCL). miR-127-3p and miR-615-3p were significantly associated with overall survival in the MCL training set. Their expression was validated in an independent MCL patient set. In comparison with Ki-67, expression of these miRs was more significantly associated with overall survival among patients with MCL. miR-127-3p was combined with Ki-67 to create a new prognostic model for MCL. A similar model was created with miR-615-3p and Mantle Cell Lymphoma International Prognostic Index scores. CONCLUSION Eleven miRs are differentially expressed between aggressive and indolent NHL. Two novel miRs were associated with overall survival in MCL and were combined with clinical prognostic models to generate novel prognostic data for patients with MCL.
    Journal of Clinical Oncology 07/2013; · 18.04 Impact Factor
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    ABSTRACT: PURPOSE: Identify subgroups of relapsed/refractory follicular lymphoma patients deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase 3 LYM-3001 study. EXPERIMENTAL DESIGN: 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary endpoint was PFS; this pre-specified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for four proteins and eight genes. RESULTS: In initial pair-wise analyses, using individual SNP genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair (PSMB1 P11A G allele, low CD68 expression [≤50 CD68-positive cells], population frequency: 43.6%), median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next anti-lymphoma therapy longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. CONCLUSIONS: Patients with PSMB1 P11A (G allele) and low CD68 expression appeared to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab.
    Clinical Cancer Research 04/2013; · 7.84 Impact Factor
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    ABSTRACT: Background The proportion of potentially eligible patients with transformed indolent non-Hodgkin lymphoma who undergo autologous stem-cell transplantation (ASCT) is unknown. There are limited data describing their outcome in the rituximab era.Patients and methodsWe reviewed 105 consecutive patients with biopsy-proven transformation referred to Princess Margaret Hospital for consideration of ASCT during 1996-2009. Patients received anthracycline or platinum-based chemotherapy with or without rituximab. Responders proceeded to stem-cell mobilization and ASCT.ResultsThe median age at transformation was 54 (range 30-65) years. Patients received a median of two chemotherapy regimens for transformation, including rituximab in 39%. Fifty patients (48%) proceeded with ASCT and 55 (52%) did not, mainly due to progressive disease (n = 42). Three-year overall (OS) and progression-free survival (PFS) post-ASCT were 54% and 42%, respectively. Patients receiving rituximab with chemotherapy before transplant had a 3-year post-ASCT OS of 71% versus 47% in those who received chemotherapy alone (P = 0.046). Patients transplanted after 2004 had a 3-year post-ASCT OS of 69% versus 39% in those receiving ASCT earlier (P = 0.009).Conclusions About half of transplant-eligible patients with transformation are able to undergo ASCT. Outcomes following ASCT appear to have improved over recent years, although the role of rituximab in this patient population requires further evaluation.
    Annals of Oncology 02/2013; · 7.38 Impact Factor
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    ABSTRACT: PURPOSETo determine whether autologous (auto) or allogeneic (allo) stem-cell transplantation (SCT) improves outcome in patients with transformed follicular lymphoma compared with rituximab-containing chemotherapy alone. PATIENTS AND METHODS This was a multicenter cohort study of patients with follicular lymphoma and subsequent biopsy-proven aggressive histology transformation. Patient, treatment, and outcome data were collected from each transplantation center and combined for analysis. A separate control group was composed of patients with transformation treated with rituximab-containing chemotherapy but not SCT. The primary end point was overall survival (OS) after transformation. RESULTS: 22 (13%) treated with alloSCT, 97 (56%) with autoSCT, and 53 (31%) with rituximab-containing chemotherapy. Five-year OS after transformation was 46% for patients treated with alloSCT, 65% with autoSCT, and 61% with rituximab-containing chemotherapy (P = .24). Five-year progression-free survival (PFS) after transformation was 46% for those treated with alloSCT, 55% with autoSCT, and 40% with rituximab-containing chemotherapy (P = .12). In multivariate analysis, patients treated with autoSCT had improved OS compared with those who received rituximab-containing chemotherapy (hazard ratio [HR], 0.13; 95% CI, 0.05 to 0.34; P < .001). On the other hand, there was no OS difference between those treated with alloSCT and rituximab-containing chemotherapy (HR, 0.44; 95% CI, 0.16 to 1.24; P = .12). OS and PFS after SCT were similar between those treated with autoSCT and alloSCT. Five-year transplantation-related mortality was 23% for those treated with alloSCT and 5% for autoSCT. CONCLUSION Patients undergoing autoSCT had better outcomes than those treated with rituximab-containing chemotherapy alone. AlloSCT did not improve outcome compared with rituximab-containing chemotherapy and was associated with clinically significant toxicity.
    Journal of Clinical Oncology 02/2013; · 18.04 Impact Factor
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    ABSTRACT: BACKGROUND: Numerous genomic abnormalities in B-cell non-Hodgkin lymphomas (NHLs) have been revealed by novel high-throughput technologies, including recurrent mutations in EZH2 (enhancer of zeste homolog 2) and CD79B (B cell antigen receptor complex-associated protein beta chain) genes. This study sought to determine the evolution of the mutational status of EZH2 and CD79B over time in different samples from the same patient in a cohort of B-cell NHLs, through use of a customized multiplex mutation assay. METHODS: DNA that was extracted from cytological material stored on FTA cards as well as from additional specimens, including archived frozen and formalin-fixed histological specimens, archived stained smears, and cytospin preparations, were submitted to a multiplex mutation assay specifically designed for the detection of point mutations involving EZH2 and CD79B, using MassARRAY spectrometry followed by Sanger sequencing. RESULTS: All 121 samples from 80 B-cell NHL cases were successfully analyzed. Mutations in EZH2 (Y646) and CD79B (Y196) were detected in 13.2% and 8% of the samples, respectively, almost exclusively in follicular lymphomas and diffuse large B-cell lymphomas. In one-third of the positive cases, a wild type was detected in a different sample from the same patient during follow-up. CONCLUSIONS: Testing multiple minimal tissue samples using a high-throughput multiplex platform exponentially increases tissue availability for molecular analysis and might facilitate future studies of tumor progression and the related molecular events. Mutational status of EZH2 and CD79B may vary in B-cell NHL samples over time and support the concept that individualized therapy should be based on molecular findings at the time of treatment, rather than on results obtained from previous specimens. Cancer (Cancer Cytopathol) 2013. © 2013 American Cancer Society.
    Cancer Cytopathology 01/2013; · 4.43 Impact Factor
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    ABSTRACT: ABSTRACT This is a randomized trial evaluating the safety and immunogenicity of one or two doses of 2009 pandemic H1N1 influenza vaccination in adults with lymphoid malignancies. Adults with a lymphoid malignancy receiving active systemic therapy, or within a year after autologous stem cell transplantation received one dose of AS03-adjuvanted A/California/7/2009(H1N1) vaccine, and randomized 21 days later to a second dose or no further vaccination. The primary outcomes were seroprotection and seroconversion rates by hemagglutination inhibition 21 and 42 days after initial vaccination. Twenty-two patients received one dose, and 20 patients received a second dose. Seroconversion rates at day 21 were 30% (one dose) and 5% (two doses), and subsequently 30% for both groups at day 42. Seroprotection rates at day 21 were 40% (one dose) and 15% (two doses), and subsequently 35% (one dose) and 40% (two doses) at day 42. Differences in serologic endpoints were not statistically significant between both study arms at day 42. Patients with low levels of B-cells (CD19-positive) had low seroconversion rates on days 21 (OR 0.74, 95% CI 0.59-0.93, p=0.043) and 42 (OR 0.12, 95% CI 0.01-1.07, p=0.058). Only 3 of the 14 patients who received rituximab achieved seroprotective titers by day 42. Patients with lymphoid malignancies did not achieve rates of seroconversion or seroprotection seen in healthy subjects despite a second dose and the use of an adjuvant. Notwithstanding suboptimal immunogenicity, seasonal and pandemic influenza vaccination should continue to be recommended.
    Leukemia & lymphoma 12/2012; · 2.61 Impact Factor
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    ABSTRACT: The purpose of the study was to assess treatment response and overall outcome in a cohort of patients with relapsed and refractory peripheral T-cell lymphoma and to compare the results with those for patients with diffuse large B-cell lymphoma treated in a similar manner. We retrospectively analyzed data of 40 consecutive adult patients with relapsed and refractory peripheral T-cell lymphoma referred to our institution for consideration of second-line chemotherapy aiming for autologous stem cell transplant between January 1999 and December 2006. A cohort of 126 patients with diffuse large B-cell lymphoma managed similarly served as a comparison group. Most (≥ 75%) patients received ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) or DHAP (cisplatin, cytosine arabinoside, dexamethasone) as salvage chemotherapy. From first relapse/progression, overall survival at 2 years was 54% (95% confidence interval [CI]: 38-76) for the peripheral T-cell lymphoma cohort and 49% (95% CI: 39-60) for the diffuse large B-cell lymphoma cohort (p = 0.098). Overall response rate to salvage chemotherapy was similar between both groups (63% vs. 52%). Post-autologous stem cell transplant, 1-year progression-free survival was 20% (95% CI: 9-48) for patients with peripheral T-cell lymphoma and 47% (95% CI: 36-61) for patients with diffuse large B-cell lymphoma. Two-year overall survival post-autologous stem cell transplant was 43% (95% CI: 26-71) and 54% (95% CI: 43-68), respectively. Patients with relapsed and refractory peripheral T-cell lymphoma and diffuse large B-cell lymphoma showed a similar response to salvage chemotherapy and overall survival. Likely due to imbalances in risk factors at relapse, progression-free survival post-autologous stem cell transplant was inferior in the peripheral T-cell lymphoma group. Strategies aiming to maintain response duration post-autologous stem cell transplant could improve the outcome of patients with peripheral T-cell lymphoma.
    Leukemia & lymphoma 08/2012; · 2.61 Impact Factor
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    ABSTRACT: Mantle-cell lymphoma (MCL) is a rare cancer, with the majority of patients (pts) presenting in stage III-IV and the outcomes are poor. To determine the curability of localized MCL, we examine stage I-II pts at our institution between 1990-2007. 26 pts with stage I (38%) and stage II (62%) were referred. Sites involved were head and neck in 73%. Five had a blastoid variant. Five patients were treated with palliative intent. Analysis was focused on pts treated with a curative intent (21 pts): 17 CT+RT, 2 RT, 2 CT followed by ASCT. 13 patients received CHOP, 5-RCHOP, 1-CVP; most received 6 cycles. The RT median dose was 35Gy and IFRT for the majority. For 21 pts treated with a curative intent, median follow up was 5.8 years. The overall response rate was 95%. Among the 19 CR/CRu pts, 9 relapsed for a 5-year relapse rate of 46%. Relapses were mainly observed at distant sites, 3 were in GI tract, 1 had both local and distant relapse. Median PFS and OS were 3.2 and 6.4years, respectively. 5-year OS was 62%. In univariate analysis, blastoid variant and stage II were prognostic factors for PFS. Multivariate analysis could not be performed due to the small sample size. With a treatment approach using combined CT+RT for stage I-II MCL, local control was achieved in 94%. Systemic relapse remains a significant problem, especially for stage II and blastoid variant. Radiotherapy should remain part of curative treatment plan in stage I-II MCL.
    Leukemia & lymphoma 07/2012; · 2.61 Impact Factor
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    ABSTRACT: We conducted a multi-institutional population-based analysis of the survival and toxicity associated with the addition of rituximab to chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL), including patients aged ≥ 80 years, who were excluded from published randomized trials. Using population-based registries in Ontario, we identified 4021 patients who received chemotherapy with or without rituximab (R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone] or CHOP) for DLBCL between 1996 and 2007, including 397 patients aged ≥ 80 years. After propensity score matching, the overall survival (OS) and significant toxicities for R-CHOP and CHOP treatment groups were compared. R-CHOP was associated with a significant increase in 5-year OS compared to CHOP alone (62% vs. 54%; hazard of death = 0·78, P = 0·0004). Survival benefit was seen in all age groups, including those aged ≥ 80 years. Patients treated with rituximab did not have a significant increase in 1-year hospitalization rates for cardiac, pulmonary, gastrointestinal or neurological diagnoses compared to those treated with CHOP alone. The addition of rituximab to CHOP improves survival in the general population of patients with DLBCL and produces early survival benefit for very elderly patients, without any significant increase in the risk of serious toxicity.
    British Journal of Haematology 06/2012; 158(4):481-8. · 4.94 Impact Factor
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    ABSTRACT: To analyze, through chart review, the efficacy of salvage radiation therapy (sRT) for relapsed or progressive Hodgkin lymphoma (HL) patients who failed autologous stem cell transplant (ASCT). Among 347 patients with recurrent/refractory HL who received ASCT from 1986-2006, 163 had post-ASCT progression or relapse. Of these, 56 received sRT and form the basis of this report. Median age at sRT was 30 years (range, 17-59 years). Disease was confined to lymph nodes in 27 patients, whereas 24 had both nodal and extranodal disease. Salvage radiation therapy alone was given in 34 patients (61%), and sRT plus chemotherapy was given in 22 (39%). Median interval from ASCT to sRT was 0.8 years (range, 0.1-5.6 years). The median dose was 35 Gy (range, 8-40.3 Gy). The sRT technique was extended-field in 14 patients (25%) and involved-field in 42 (75%). The median follow-up from sRT was 31.3 months (range, 0.2-205.5 months). Overall response rate was 84% (complete response: 36%; partial response: 48%). The median overall survival was 40.8 months (95% confidence interval, 34.2-56.3 months). The 5-year overall survival was 29% (95% confidence interval, 14%-44%). The 2-year progression-free survival (PFS) was 16%; the 2-year local PFS was 65%, whereas the 2-year systemic PFS was 17%. The 1-year PFS was higher in patients in whom all diseased sites were irradiated (49%) compared with those in whom only the symptomatic site was treated (22%, P=.07). Among 20 alive patients, 5 were disease free (at 6.4, 6.8, 7.4, 7.9, and 17.1 years). For patients with HL who fail ASCT, a selective use of RT provides a durable local control rate of 65% at 2 years and should be considered as part of the standard management plan for the palliation of incurable HL. Occasionally irradiation of truly localized disease can lead to long-term survival.
    International journal of radiation oncology, biology, physics 06/2012; 84(3):e329-35. · 4.59 Impact Factor
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    ABSTRACT: Mucosa-associated lymphoid tissue (MALT) lymphoma is very rare in children. We report the first case of pediatric thymic MALT lymphoma in an adolescent Asian girl. She presented with chest pain, dyspnea, and low-grade fever. A large anterior mediastinal mass was biopsied that confirmed the diagnosis of MALT lymphoma with trisomy 18. The patient had secondary immunodeficiency with low NK cell count and high IgA and IgG levels. Because of the advanced stage and the presence of trisomy 18, she was treated with cyclophosphamide, vincristine, prednisone, and rituximab, followed by involved-field radiotherapy. She is currently undergoing maintenance therapy with rituximab and remains in complete remission at 13 months from diagnosis. Thymic MALT lymphoma should be suspected in any Asian child with a cystic thymic mass and autoimmune disease or hyperglobinemia. Because of the slow proliferation rate of this type of lymphoma, a long-term follow-up is needed.
    Journal of Pediatric Hematology/Oncology 03/2012; 34(7):552-5. · 0.97 Impact Factor

Publication Stats

3k Citations
1,100.50 Total Impact Points

Institutions

  • 2001–2014
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2012
    • Hôpital Maisonneuve-Rosemont
      Montréal, Quebec, Canada
  • 2005–2012
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 2011
    • BC Cancer Agency
      Vancouver, British Columbia, Canada
  • 2002–2011
    • University Health Network
      • Department of Medical Oncology
      Toronto, Ontario, Canada
  • 1991–2011
    • University of Toronto
      • • Department of Medicine
      • • Department of Radiation Oncology
      • • Faculty of Medicine
      Toronto, Ontario, Canada
  • 2008
    • SickKids
      • Division of Hematology/Oncology
      Toronto, Ontario, Canada
  • 2007
    • McGill University
      Montréal, Quebec, Canada
  • 2004
    • Ontario Institute for Cancer Research
      Toronto, Ontario, Canada
  • 1992–2000
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 1990
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada