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  • 1
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    Excellent real‐world outcomes of adults with Burkitt lymphoma treated with CODOX ‐M/ IVAC plus or minus rituximab
    Wiley ; 2018
    In:  British Journal of Haematology Vol. 181, No. 6 ( 2018-06), p. 782-790
    Details
    In: British Journal of Haematology, Wiley, Vol. 181, No. 6 ( 2018-06), p. 782-790
    Abstract: 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), as did those under 60 years with 5‐year PFS 82% ( P  = 0·005) and OS 86% ( P  = 0·002), which remained significant in multivariate analysis [ PFS : hazard ratio ( HR ) 3·36, P  = 0·018; OS HR 4·03, P  = 0·012]. Incorporation of high‐dose systemic methotrexate also significantly affected multivariate survival outcomes ( OS HR 0·28, P  = 0·025). Stem cell transplant in first remission had no effect on OS or PFS . This large, real‐world analysis of BL patients treated with CODOX ‐M/ IVAC ± rituximab demonstrates excellent survival outcomes comparable to clinical trials. These results help to serve as a benchmark when comparing curative therapies for BL patients as novel regimens are incorporated into clinical practice.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    URL: Article
    DOI: 10.1111/bjh.2018.181.issue-6
    DOI: 10.1111/bjh.15262
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 2018
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  • 2
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    Prior Rituximab Reduces Relapse and Improves Survival Following High Dose Chemotherapy and Stem Cell Transplantation for Relapsed Composite Low and Intermediate Grade (Including Transformed) Lymphoma.
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 3662-3662
    Details
    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
    URL: Article
    DOI: 10.1182/blood.V108.11.3662.3662
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
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  • 3
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    Long Term Results of Myeloablative Allogeneic Stem Cell Transplantation Using Related and Unrelated Donors in Patients with Relapsed Composite Low and Intermediate Grade (Including Transformed) Lymphoma.
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 3139-3139
    Details
    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
    URL: Article
    DOI: 10.1182/blood.V108.11.3139.3139
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
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    Outcome Of Patients With Double-Hit Lymphomas Treated With CODOX-M/IVAC + R Followed By Hematopoietic Stem Cell Transplantation In British Columbia
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 1788-1788
    Details
    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
    URL: Article
    DOI: 10.1182/blood.V122.21.1788.1788
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 5
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    Daclizumab Therapy Improves Outcome in Steroid Refractory Acute Graft Versus Host Disease (aGVHD).
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 5092-5092
    Details
    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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.5092.5092
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 6
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    Long-term disease-free survival of patients with advanced follicular lymphoma after allogeneic bone marrow transplantation : Long-term DFS of Patients with Follicular NHL Post-allo BMT
    Wiley ; 2004
    In:  British Journal of Haematology Vol. 127, No. 3 ( 2004-11), p. 311-321
    Details
    In: British Journal of Haematology, Wiley, Vol. 127, No. 3 ( 2004-11), p. 311-321
    Type of Medium: Online Resource
    ISSN: 0007-1048
    URL: Issue
    URL: Article
    DOI: 10.1111/bjh.2004.127.issue-3
    DOI: 10.1111/j.1365-2141.2004.05194.x
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 2004
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  • 7
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    Haematopoietic stem cell transplantation as primary therapy of sporadic adult Burkitt lymphoma*
    Wiley ; 2006
    In:  British Journal of Haematology Vol. 133, No. 6 ( 2006-06), p. 634-637
    Details
    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
    URL: Article
    DOI: 10.1111/bjh.2006.133.issue-6
    DOI: 10.1111/j.1365-2141.2006.06080.x
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 2006
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  • 8
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    Myeloablative Allogeneic Stem Cell Transplantation for Relapsed Composite Low and Intermediate Grade Lymphoma Is Not Superior to Autologous Stem Cell Transplantation - Reduced Relapse Risk Is Offset by Higher Treatment Related Mortality.
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 3039-3039
    Details
    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
    URL: Article
    DOI: 10.1182/blood.V108.11.3039.3039
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
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  • 9
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    Improved Survival In Adults With Mixed-Phenotype Acute Leukemia Following Stem Cell Transplantation (SCT): A Single Centre Experience
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 5540-5540
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5540-5540
    Abstract: Biphenotypic acute leukemia (BAL) is a rare subtype of leukemia accounting for 1% to 4% of all acute leukemias. They are associated with unfavorable outcome especially in adult population when treated with standard chemotherapy alone. Management issues like type of induction therapy, consolidation strategies, and role of high dose chemotherapy with stem cell transplantation remain unclear. Methods A retrospective review of 28 patients (pts) with BAL who were treated in Vancouver between 1984 and 2012 was performed. Diagnoses were confirmed according to WHO 2008 guidelines by two hematopathologists who independently reviewed morphology, immunophenotyping and in few cases immunohistochemistry. Kaplan-Meier estimates were utilized for event free survival (EFS) and overall survival (OAS). Characteristics There were 23 males and 5 females with a median age of 47 (range 17 - 75) years. Median white cell count (WCC) at presentation was 7.7 x 109(range: 0.9 to 192x109)/L. Immunophenotyping revealed “Myeloid + B-lymphoid” pattern in 13 pts (46.4%), “Myeloid + T-lymphoid” pattern in 13 pts (46.4%), “Myeloid + B-lymphoid + T-lymphoid” pattern in 1 pt (3.6%) and “T-lymphoid + B-lymhoid” pattern in 1 pt (3.6%). Cytogenetic studies revealed Normal karyotype in 6 pts (21.43%), complex karyotype in 6 pts (21.43%), Philadelphia chromosome positivity in 3 pts (10.71%), MLL rearrangement in 1 pt (3.57%) and other chromosomal abnormalities in 9 pts (32.14%). Cytogenetic studies failed in 2 pts (7.14%) and no data was available in 1 pt (3.57%). Induction therapy was of AML type in 5 pts (17.9%), ALL type in 8 pts (28.6%), and combination of AML and ALL type in 15 pts (53.6%), and 2 of the 3 pts with Philadelphia positivity also received imatinib (one patient was treated in the pre-Imatinib era) with induction chemotherapy. Twenty (71.43%) pts achieved complete remission (CR), 16 with one cycle and 4 with two cycles. Twelve pts went on to receive high dose chemotherapy with SCT. Stem cell source was autologous in 2 pts (16.7%), related donor in 3 pts (25%), unrelated donor in 6 pts (50%), and unrelated cord blood in 1 pt (8.3%). Eleven of 12 pts were in first CR and one was in second CR before SCT. Conditioning chemotherapy was TBI-based in 7 pts and busulfan based in 5 pts. Results ALL treatment induced a remission in 45%, AML therapy in 0% and 53% responded to combination therapy. EFS and OAS estimates for all 28 patients at 15 years were 29% (95% CI 13% to 48%) and 40% (95% CI 21% to 58%) respectively. Patients receiving high dose chemotherapy and SCT had significantly improved OAS of 63% (95% CI 29% to 85%) vs. 23% (95%CI 6% to 46%) for those receiving only chemotherapy (P = .019). OAS for pts with presenting WCC of 〈 30x109 was significantly better compared to pts with presenting WCC of 〉 60x109 (54% vs. 0%, p = .039).”Myeloid + B lymphoid” group had better OAS estimates compared to “Myeloid + T- lymphoid” group (59% vs. 29% respectively, but not statistically significant, p= 0.1135). Type of induction chemotherapy, and age at diagnosis were not statistically significant outcome predictors. Conclusion Although a small sample size, this study would suggest that adult patients with BAL who achieve a CR with standard chemotherapy should be considered for high dose chemotherapy and stem cell transplantation. This modality of treatment gives them the greatest probability of long term overall survival. Disclosures: Sutherland: Celgene: Honoraria; Janssen : Honoraria; Novartis: Honoraria. Toze:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.5540.5540
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 10
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    Allogeneic Stem Cell Transplantation as Treatment for Relapsed and High-Risk Peripheral T-Cell Lymphoma.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 3040-3040
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 3040-3040
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.3040.3040
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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    detail.hit.zdb_id: 80069-7
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