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  • 1
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4662-4662
    Abstract: Background: The myelodysplastic syndromes (MDS) encompass a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic and ineffective blood cell production leading to cytopenia and a variable risk of transformation to acute myeloid leukemia. The natural history of patients (pts) with MDS is variable and several prognostic scoring systems have been developed to guide treatment decisions. The revised IPSS (IPSS-R) score is commonly used in practice to predict outcome in newly diagnosed pts as well as in predicting their transplant outcomes. It remains unclear however whether improving IPSS-R pre allogeneic transplant (allo-SCT), using different therapeutic strategies, is associated with better clinical outcomes post-transplant. Methods: The Leukemia/BMT Program of British Columbia database was queried to identify all pts with MDS who had undergone an allo-SCT between Feb 1997 and April 2013. Pertinent information on clinical features and outcomes were then retrospectively reviewed. IPSS-R was calculated at MDS diagnosis (dx) and then re calculated prior to transplant. Outcomes of pts who had improvement in IPSS-R were then compared to those with no improvement or worsened IPSS-R score. Overall survival (OS) and Event free survival (EFS) were estimated using the Kaplan-Meier method and a competing risk analysis was used to calculate relapse and non-relapse mortality (NRM). Univariate and multivariate analyses were conducted. Log-Rank test was used to determine the p value. Results: We identified 138 pts who have undergone allo-SCT with the following characteristics: median age at transplant was 49 years (yrs) (range 17-66); 76 (55%) were male; 121 pts (88%) underwent myeloablative (MA) conditioning, 68 (49%) related donor and 70 (51%) unrelated donors out of which 43 (61%) were matched and 27 (39%) were mismatched. The source of stem cells were: peripheral blood n=101 (73%), bone marrow n=35 (25%) and cord blood n=2 (1%). The median interval from dx to transplant was 128 days. The median follow up (FU) of live pts was 7.3 yrs (range 1.5-17.4). Acute graft vs. host disease (aGVHD) grade 2 or higher was present in 74 (54%), chronic graft vs. host disease (cGVHD) was present in 94 (68%). During the time of FU 83 (60%) of pts had died. Relapse occurred in 41 (30%). Causes of death were: relapse n=39; GVHD n=20; regimen related n=11; infection n=5 and other causes, n=9. Baseline characteristics of all pts are shown in table 1. In 12 (9%) pts, the IPSS-R could not be calculated either because cytogenetics failed or bone marrow biopsy pre transplant was not done. At the time of transplant 85 (62%) pts had blasts 〈 5%, 38 (28%) had 5-20% and 10 (7%) had blasts 〉 20% and blasts count was unknown in 5 pts. IPSS-R improved in 62 (45%), worsened in 23 (17%), no change 41 (30%) and unknown in 12 (9%). Type of treatment was chemotherapy in 55 (40%), best supportive care in 80 (58%) and immunosuppressive therapy (IST) in 3 (2%). The OS and EFS for all pts were 34% and 33%, respectively. There was no difference in outcome between pts who have undergone MA vs non-MA, OS 34% and 39% (p=0.63) and EFS 34% and 32% (p=0.86), respectively. OS was not statistically different between pts with improved IPSS-R vs worsened vs unchanged, 30% vs 22% vs 40%, p= 0.63 (see figure 1). EFS was 30% vs 21% vs 40%, p=0.53, respectively. Relapse was 36% vs 53% vs 31%, p=0.35 and non-relapse mortality was 54% vs 57% vs 42%, p=0.75, respectively. There was no difference in OS and EFS between pts treated with chemotherapy vs supportive care with OS of 40% vs 41%, p=0.63 and EFS of 33% vs 32%, p=0.46, respectively. OS and EFS for grade 2 or higher aGVHD were 34% vs 32%, p=0.13 and 32% vs 32%, p=0.22, respectively. Figure 2 shows OS for Pts with blast 〈 5% vs 5-20% vs 〉 20% at transplant. Relapse of pts with blasts 〈 5 vs 5-20 vs 〉 20 at the time of transplant was 23% vs 69% vs 66%, p=0.0004, respectively. On multivariate analysis, only three factors were associated with worse OS and EFS which were: cytogenetics at dx, blast count at transplant and absence of cGVHD. Conclusion: Improving IPSS-R before allogeneic transplant does not translate into better clinical outcome. The IPSS-R cytogenetic risk group at the time of diagnosis and blast count at transplant are highly predictive of post-transplant outcomes. Patient characteristics Patient characteristics Disclosures 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 2
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3662-3662
    Abstract: The effect of prior exposure to rituximab (ritux) on relapse (REL) and survival following stem cell transplantation (SCT) in patients (pts) with REL composite low and intermediate grade non-Hodgkin lymphoma (L/I-NHL) is unknown. Fifty-four pts with REL L/I-NHL underwent high-dose chemotherapy (CT) and SCT Jan ’89 to June ’05. Follow-up is complete to April ’6 with a median of 32 mo. Ritux was added to CT regimens since 2001 and given at 375 mg/m2. Eighteen pts received ritux at initial diagnosis of NHL or after REL with salvage CT prior to SCT. Pts proceeded to high dose CT with allogeneic (allo) (n=12) or autologous (auto) SCT (n=6). This group was compared with a group of pts not receiving ritux pre-SCT (n=36)(Table 1). Eleven pts (61%) are alive in the ritux group compared with 11 pts (31%) in the non-ritux group. The 2 and 4-y OS for pts who received ritux were 52% and 52%, vs 36% and 24% (p=.12, RR=.52) for pts who did not receive ritux. The EFS were significantly different with 2 and 4-y EFS for the ritux group 56% and 56% vs 24% and 18% (P=.038, RR=.42) for the non-ritux group (figure 1). No effect was seen on TRM. The risk of REL post SCT was significantly lower in the ritux group (p=.017)(figure 2). Two of 18 pts (11%) had NHL REL in the ritux vs 18 of 36 (50%) in the non-ritux group. The hazard rate of REL in pts who received ritux was 20% that of pts in the non-ritux group. Significance maintained in multivariate analysis (p=.016). No impact was seen on graft-versus-host disease (GVHD). Fifty percent and 61% of pts developed acute GVHD grades 2–4 and 50% and 64% of pts developed chronic GVHD in the ritux and non-ritux groups respectively. In conclusion, prior treatment with ritux in pts with relapsed composite L/I-NHL undergoing SCT was associated with reduced risk of REL and improved survival without associated increase in toxicity. Further analysis is underway to clarify the nature of this important finding. Table 1: Clinicopathological characteristics of ritux and non-ritux groups Parameter$ Rituximab group, n=18 (%) Non-rituximab group, n=36 (%) $ all p values are 〉 0.1. *at diagnosis Median age at SCT 48 y 44 y M:F 2.6:1 1.6:1 Allo-SCT 12(67) 28(78) BM involvement* 10(56) 22(61) B symptoms* 7(39) 10(28) Prior purine analogue therapy 8(44) 11(31) Residual disease prior to SCT 9(50) 14(39) TBI in conditioning 13(72) 30(83) Figure Figure Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 3
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3039-3039
    Abstract: No reports compare autologous and allogeneic stem cell transplantation (auto-SCT vs allo-SCT) for patients (pts) with relapsed (REL) composite low and intermediate grade non-Hodgkin lymphoma (L/I-NHL). Fifty four pts with composite L/I-NHL (30 transformed, 16 composite(same site), 8 discordant(different sites)) who underwent allo (n=40) or auto-SCT (n=14) from Jan ‘89 to June ‘05 were evaluated (Table 1) to compare long-term results. Twenty pts (37%) (11/40 allo and 9/14 auto) are alive with median follow-up of 32 months (range 10–87). The 2 and 5-y OS for the whole group were 43% [95% confidence interval: 28–56%] and 29% [14–46%] respectively; the 2 and 5-y EFS 40% [26–53%] and 24% [11–39 %] . 5-y OS for the auto and allo-SCT were 51% and 23% respectively (p=.09)(Fig. 1). The 2 and 5-y EFS for the allo vs auto-SCT groups were 36% [24–55%] vs 54% [33–89%] and 27% vs 23% (p=0.4). Thirty four pts (63%) died; 18 (33%) with REL NHL and 16 (30%) with TRM. TRM was due to GVHD (n=7), infection (n=6), cerebral edema (n=1) and veno-occlusive disease (n=1). All but one (cerebral edema) TRM deaths occurred post allo-SCT. The cumulative incidence (CI) of TRM and REL for the whole group were 37% [17–57%] and 47% [30–64%] . The CI of TRM for allo and auto-SCT were 47% [20–74] and 8% [0–23%] respectively (p=.009)(Fig. 2). Twenty pts (37%) relapsed post SCT (14/40, 35% allo and 6/14, 43% auto). CI of REL NHL for allo and auto-SCT were 42% [23–61%] and 65% (p=.008)(Fig. 2). In conclusion EFS for composite L/I-NHL is low post auto-SCT due to a high relapse rate despite acceptable TRM. While relapse risk is significantly lower post allo-SCT, this advantage is offset by a higher TRM in these pts. Future attempts to reduce TRM while preserving the allogeneic graft vs lymphoma effect may be beneficial. Table 1. The clinicopathological characteristics of 54 patients treated with auto and allo-SCT for relapsed composite L/I-NHL Parameter Allo-SCT n=40(%) Auto-SCT n=14(%) * at diagnosis Age: Range (Median) 28–57(44) 25–59(49) M:F 2:1 1.3:1 Diagnosis Transformed lymph. 25(63) 5(36) Discordant lymph. 7(17) 1(7) Composite lymph. 8(20) 8(57) Initial Stage I/II 4(10) 6(42) III/IV 36(90) 8(58) B symptoms* 11(28) 6(43) BM involvement* 29(73) 3(21) IPI* 0–1 18(45) 11(79) 2–3 21(53) 3(21) 4–5 1(2) 0 Prior treatment CHOP 33(83) 14(100) Purine analogue 17(43) 2(14) Rituximab 12(30) 6(43) Fig 1: OS for auto/alle groups Fig 1:. OS for auto/alle groups Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 4
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3139-3139
    Abstract: Patients (pts) with relapsed (REL) transformed non-Hodgkin lymphoma (NHL) have poor outcome with conventional therapies. Although the role of autologous (auto) stem cell transplantation (SCT) has been previously described, there is scarce literature about allogeneic (allo) SCT in this setting. Forty pts with REL composite low/intermediate (L/I) NHL (25 transformed, 8 composite (same site) and 7 discordant (different sites)) underwent allo-SCT Jan ’89 to June ’05. Fifteen pts (38%) received stem cells from unrelated donors (UD) (12 matched and 3 with one antigen mis-match [1AgMM]). Six of 15 pts (40%) in the UD group are alive including one pt post 1AgMM SCT. 25 pts (62%) had matched sibling allo-SCT and 5 (20%) pts are still alive. Twenty-nine of 40 pts (73%) died, with REL NHL (n=15, 38%) or treatment related mortality (TRM) (n=14, 35%). The 2 and 5-year probability of OS were 39% [95% CI: 26–58%] and 23% [10–49%] respectively; of EFS 36% [24–55%] and 23% [11–46%] . Univariate analysis (UVA) showed presence of residual (res) NHL prior to allo-SCT as a poor prognostic factor for OS and EFS with p value of 0.029 (HR=2.2) and 0.011 (HR=2.5) respectively. No survival difference was seen between patients treated with related or UD stem cells. On multivariate analysis (MVA), development of aGVHD grades 2–4 had a significantly negative impact on both OS and EFS (for OS: p=0.006, HR=1.46, for EFS: p=0.01, HR=1.37) as did res disease prior to SCT (for OS: p=0.04, HR=2.2, for EFS: p=0.02, HR=2.4). Age 〉 46 years was a significant risk factor for TRM on UVA (p=0.02, HR=3.3) and MVA (p=0.07, HR=2.9). MVA also showed development of cGVHD as a significant risk factor for TRM (p=0.001, HR=1.8). No difference in TRM was seen between related and UD SCT. Pts with res NHL at SCT had a higher risk of REL NHL (p=0.008, HR=5), as did pts who were chemotherapy resistant (no change in the tumor mass) pre-SCT (p=0.002, HR=3.9). Inclusion of TBI in the conditioning regimen significantly reduced the risk of REL NHL (p=0.01, RR=0.22). Prior rituximab therapy was associated with reduced REL risk, although this was not statistically significant (p=0.06, HR=0.82). CGVHD was significantly protective against REL in MVA (p=0.03, HR= 0.8), and res NHL at SCT was associated with increased REL (p=0.003, HR= 7). Stem cell dose (mononuclear cells) 〉 3X108/kg was the only significant risk factor for development of cGVHD in UVA (p=0.04, HR=0.4) and MVA (p=0.05, HR=0.4). In conclusion, this is the largest report on the utility of allo-SCT (inculding UD-SCT) in patients with REL composite L/I-NHL. Survival was similar in pts receiving stem cells from related and unrelated donors. UVA and MVA analysis revealed multiple significant risk factors for survival, TRM, development of cGVHD and relapse which should be taken into consideration for future allo SCT pts. Development of chronic, but not acute GVHD was protective for NHL relapse, supporting the action of a graft vs lymphoma effect in this population.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 5
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1788-1788
    Abstract: 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. Methods 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. Results 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%. Conclusion 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. Disclosures: 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 6
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 5092-5092
    Abstract: Steroid refractory aGVHD following allogeneic stem cell transplant (SCT) is associated with a long-term event-free survival (EFS) of less than 20%. Daclizumab is a humanised monoclonal antibody specific for the Tac subunit of the Interleukin-2 (IL-2) receptor. It inhibits IL-2 binding and is thought to be more specific for alloreactive lymphocytes than pan-T cell antibodies. Limited phase II trials using daclizumab for steroid refractory aGVHD have demonstrated 50–60% complete response (CR) rates, though its safety and efficacy as primary aGVHD treatment has recently been questioned. We examined the Vancouver experience with daclizumab in the management of steroid refractory aGVHD. Between 8/00 and 2/04, 35 patients with steroid refractory aGVHD were treated with daclizumab. Male:female ratio was 1.7:1. Median age was 42 years (17–53). Pretransplant diagnoses were AML (n=7), ALL (n=6), CML (n=6), MDS (n=5), NHL (n=6), MM (n=4) and Myelofibrosis (n=1). One patient with relapsed AML post-SCT developed aGVHD following DLI. Stem cell source was matched unrelated bone marrow (BM) (n=11) or peripheral blood (PB) (n=8), mismatched unrelated BM (n=6) or PB (n=3), matched related BM (n=2) or PB (n=4), and mismatched related BM (n=1). Twenty eight pts were conditioned with Cyclophosphamide/TBI. CSP/MTX aGVHD prophylaxis was used in all pts and initial aGVHD therapy consisted of Methylprednisolone 2 mg/kg IV. Grade I-II aGVHD developed in 18/35 (51%) pts and grade III-IV in 17/35 (49%) pts. Median onset of aGVHD was 18 (6–49) days post transplant. Steroid refractory pts received daclizumab 1 mg/kg IV (maximum dose 100mg) on days 1, 4, 8, 15 and 22 at a median of 40 (18–94) days post transplant. Daclizumab response was assessed at day 42 following its initiation. A CR was defined as a return to stage/grade 0 aGVHD and a PR as a reduction of ≥ 1 aGVHD stage/grade without need for additional therapy. There were no significant infusional complications. One patient died during the response assessment period (regimen related pulmonary toxicity). Overall response rate (ORR) was 25/35 (73%), with 15/25 (44%) achieving a CR and 10/25 (29%) a PR. Response was most likely in pts with skin involvement. ORGAN ORR CR PR NR SKIN 25/33 (76%) 18/33 (55%) 7/33 (21%) 8/33 (24%) GUT 15/23 (65%) 7/23 (30%) 8/23 (35%) 8/23 (35%) LIVER 8/14 (57%) 3/14 (21%) 5/14 (36%) 6/14 (23%) SKIN ALONE 9/11 (82%) 8/11 (73%) 1/11 (9%) 2/11 (18%) Twenty four (68%) pts developed limited (n=8) or extensive (n=15) chronic GVHD. The 3-year OS and EFS rates were 35% (95% CI 17–53%) and 28% (95% CI 12–47%), respectively. Female patients had a significantly poorer OS (p=0.0064) and EFS (p=0.0112) as did those pts receiving SCT from female donors (p=.0333 / 0.0456). Eleven patients (31%) received antithymocyte globulin (ATG) in addition to daclizumab. In this subgroup, aGVHD response was more likely but ATG treated patients had increased CMV antigenemia rates during the treatment response period (p=0.01), and a significantly lower EFS (p=0.0064) and OS (p=0.0123). Daclizumab is an effective agent for steroid refractory aGVHD especially if limted to the skin. Long-term survival appears to be superior in pts treated with this agent although its use along with ATG may compromise pt outcome.
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    ISSN: 0006-4971 , 1528-0020
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    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 7
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5852-5852
    Abstract: 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 of 11 months from primary diagnosis (range 4-64) with the following clinical features: median age at transplant was 45 years (range 16-58 years); 24 (67%) were male; 32 (89%) patients had advanced stage disease; 22 (61%) had B-symptoms at diagnosis. Bone marrow involvement detected in 13/34 (38%) patients. Histological diagnosis based on the WHO 2008 classification were: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) n=15 (42%); anaplastic large cell lymphoma (ALCL) n=7 (19%) out of which three were ALK positive, angioimmunoblastic T-cell lymphoma (AITL) n=6 (17%), hepatosplenic T-cell lymphoma n=5 (14%), enteropathy associated T-cell lymphoma type I n=1, advanced primary cutaneous gamma-delta T-cell lymphoma n=1 and Sezary syndrome n=1. Ten patients (28%) underwent allo-SCT as part of planned primary therapy after achieving their first remission [6 were in complete remission 1 (CR1) and 4 were in partial remission 1 (PR1)] , whereas 26 patients (72%) underwent allo-SCT for relapsed/refractory disease. CHOP was administered in 19 patients (53%) as the primary therapy. 17 (47%) patients received alternative chemotherapy regimen due to patient and/or physician preference. The clinical status at the time of transplantation was CR in 12 patients (33%), relapsed sensitive disease n=10 (28%), relapsed untreated n=5 (14%), partial remission (PR) in 5 (14%), primary progressive disease n=3 (8%) and relapsed resistant disease n=1 (3%). Thirty two patients (89%) underwent myeloablative conditioning, 4 (11%) underwent reduced intensity conditioning (RIC). The conditioning regimens included: cyclophosphamide/TBI n=24 (67%), busulfan/cyclophosphamide n=5 (14%), fludarabine containing reduced intensity n=4 (11%), and other regimens n= 3 (8%). With a median follow-up of alive patients from the time of allo-SCT of 69 months (range 1-186 months). At last follow-up, 17 (47%) patients have died, 6 from disease relapse, 5 from graft vs host disease (GVHD), 2 from regimen related toxicity and 4 from other causes. Nineteen patients (53%) still alive at last follow up post-transplant of which 14 (39%) still in remission. The 5-year event free survival (EFS) and overall survival (OS) from the time of allo-SCT of all patients were 43% and 63%, respectively. For PTCL-NOS the 5-year EFS and OS were 52% and 69%, respectively. Table 1 summarizes the patients' characteristics. Figures 1 and 2 shows the Kaplan-Meier curves for OS and EFS respectively. Conclusion: Allo-SCT can be effective strategy in select patients with relapsed/refractory PTCL and those with high risk histologies in the upfront setting PTCL with an acceptable toxicity. Disclosures 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 8
    In: British Journal of Haematology, Wiley, Vol. 127, No. 3 ( 2004-11), p. 311-321
    Type of Medium: Online Resource
    ISSN: 0007-1048
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    Publisher: Wiley
    Publication Date: 2004
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  • 9
    In: British Journal of Haematology, Wiley, Vol. 133, No. 6 ( 2006-06), p. 634-637
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 1475751-5
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  • 10
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 2764-2764
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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