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  • 1
    In: British Journal of Haematology, Wiley, Vol. 161, No. 4 ( 2013-05), p. 578-586
    Type of Medium: Online Resource
    ISSN: 0007-1048
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    Language: English
    Publisher: Wiley
    Publication Date: 2013
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  • 2
    In: Blood, American Society of Hematology, Vol. 103, No. 4 ( 2004-02-15), p. 1548-1556
    Abstract: Data on the application of donor lymphocyte infusions (DLIs) following reduced-intensity transplantation (RIT) remain limited. Persistence of host antigen-presenting cells might increase the efficacy or toxicity of cellular immunotherapies. We report the results of dose-escalating DLIs in 46 patients undergoing RIT, who received a total of 109 infusions to treat mixed chimerism or residual or progressive disease. Diagnoses were myeloma (n = 19), Hodgkin lymphoma (n = 13), non-Hodgkin lymphoma (n = 10), and other (n = 4). Thirty-two had an HLA-matched family donor and 14 an unrelated donor. Grades II to IV graft-versus-host disease (GVHD) occurred in 5 sibling and 7 unrelated donor recipients. GVHD was more common (P = .002), occurred at lower T-cell doses, and was more severe in the unrelated donor cohort. Conversion from mixed to multilineage full donor chimerism occurred in 30 of 35 evaluable patients. Presence of mixed chimerism in the granulocyte lineage at the time of DLI did not predict for chimerism response or GVHD. Disease responses occurred in 63% of patients with myeloma and 70% of those with Hodgkin lymphoma and were not predicted by changes in chimerism. These data support the presence of clinically relevant graft-versus-Hodgkin activity and indicate that DLI may be associated with a significantly increased toxicity in unrelated compared to sibling donor transplant recipients receiving identical treatment protocols.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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  • 3
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 401-401
    Abstract: Allogeneic transplantation with reduced intensity conditioning is increasingly being used in patients with non-Hodgkin’s Lymphoma (NHL) who fail standard therapy. We report extended follow-up on 121 patients with NHL, who underwent allogeneic transplantation with reduced intensity conditioning at 8 UK centres. Conditioning was with fludarabine 150mg/m2, melphalan 140mg/m2 and alemtuzumab (60–120mg). Cyclosporin A was administered at 3mg/kg from day-1, and stem cell source was bone marrow or PBSC. Diagnoses were in 3 categories: low grade follicular NHL (n=50), mantle cell lymphoma (n=21), and high-grade NHL (n=50, including transformed low grade disease n=15). Donors were HLA-matched siblings in 75 (62%), and unrelated in 46 (38%), of whom 18 were HLA-mismatched at up to 3/10 loci. 48% of patients had failed previous autologous transplantation. Median follow-up was 35 months (1–78). For the group with low grade follicular NHL (n=50), estimated overall survival (OS) was 76% at 1yr and 67% at 4yrs, and non-relapse mortality (NRM) was 16% at 4yrs. Disease relapse or progression occurred in 12 patients, of whom 8 received donor lymphocyte infusions (DLI), with responses in 6. Current progression-free survival (cPFS) is 68% at 4yrs. For the group with mantle cell lymphoma (n=21), estimated OS was 83% at 4yrs, NRM was 11% at 4yrs and relapse or progression occurred in 6 patients. Three patients received DLI, with non-sustained responses in 2. Current PFS is 43% at 4yrs. For high-grade NHL (n=50), estimated OS was 52% at 1yr and 45% at 4yrs. Prior autologous transplantation was common in this group (72%), and NRM was higher at 34% at 1yr and 40% at 4yrs. Progression/relapse occurred in 15 patients, of whom 10 received donor lymphocytes, with responses in 5. Current PFS is 48% at 1yr and 43% at 4yrs. These results, from patients who were often heavily pre-treated, including having failed autologous transplantation, provide encouraging evidence to support the application of reduced intensity allogeneic transplants in NHL. NRM in low grade follicular or mantle cell lymphoma is low, consistent with the use of T cell depletion, and graft-versus-lymphoma effects can be induced with DLI in a subset of cases. The data in follicular lymphoma, in particular, supports consideration of this therapy earlier in the disease. In high-grade disease, NRM appears to be higher, but durable remissions are attainable in a proportion of patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 2053-2053
    Abstract: The role of T cell depletion in allogeneic stem cell transplantation for acute myeloid leukemia (AML) remains controversial. This study describes the results of an alemtuzumab-containing myeloablative regimen used to transplant 51 consecutive patients with hematological malignancy. Diagnoses were AML (n=48) of which 8 were secondary (6 transformed MDS; 2 therapy-related AML) or MDS (n= 3). Median age at transplant was 38yrs (range 13–57), and 29 patients had unrelated donors. Sixteen patients were HLA-mismatched at up to 3/10 loci (8x1; 7x2; 1x3). The majority of patients (39/51; 76%) were high-risk for relapse, as defined by induction failure ( 〉 15% blasts after one course of induction chemotherapy or 〉 5% blasts after 2 courses), adverse cytogenetics, 〉 CR1, or secondary disease. Six patients (12%) had residual detectable disease at the time of transplant despite at least 3 courses of induction therapy. Patients received cyclophosphamide 120 mg/kg and fractionated total body irradiation (14.4 Gy). Those with unrelated donors also received fludarabine 90 mg/m2. Stem cell source was bone marrow in 11 patients and PBSC in the remaining 40. Stem cells underwent in vitro T cell depletion using 20mg alemtuzumab added to the bag. All patients also received cyclosporin A for GvHD prophylaxis. Median follow-up for the surviving patients is 29 months (range 3–49). The estimated event-free survival is 70% at 1yr and 58% at 3yrs. Acute GvHD grade II occurred in 8% (no grade III–IV) and extensive chronic GvHD in 22%. Non-relapse mortality was 17% at 1yr and 25% at 3yrs, and relapse has occurred in 9 patients, giving an estimated relapse risk of 21% at 3yrs (24% in high-risk patients, n=39). For EFS and NRM, the only significant variable is age 〉 45yrs at transplant, with no significance for donor type or presence of HLA mismatch. For patients aged ≤ 45yrs at transplant (n=42), of whom 81% were high risk for relapse, the outlook is very good with estimated NRM of 15% at 3yrs, and EFS of 69%. Use of this regimen therefore permits the successful transplantation of younger patients with high-risk disease and HLA-matched or mismatched unrelated donors, with minimal acute GvHD, low non-relapse mortality and no evidence of an excessive relapse rate, when compared to regimens without T cell depletion.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
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    detail.hit.zdb_id: 80069-7
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  • 5
    In: Blood, American Society of Hematology, Vol. 99, No. 12 ( 2002-06-15), p. 4642-4644
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2002
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 657-657
    Abstract: Hodgkin’s Lymphoma is curable with primary therapy in the majority of patients. For those with relapsed or refractory disease, salvage with high dose chemotherapy plus autologous stem cell rescue is effective for a significant proportion. Patients relapsing following autologous stem cell transplantation, however, have an extremely poor prognosis. Allogeneic transplantation with conventional conditioning has proved excessively toxic in this setting, and reduced intensity conditioning has therefore been introduced, with encouraging preliminary results. This is a study of 72 patients relapsing following autologous transplantation, analysed in 2 groups. One group (A: n=38) then underwent allogeneic transplantation with reduced intensity conditioning at 6 UK centres (1998–2004), with alemtuzumab 100mg, fludarabine 150mg/m2 and melphalan 140mg/m2. Donors were HLA-matched related in 63% of cases, and unrelated in the remaining 37%. The second group (B: n=34) is a control cohort, who relapsed before the advent of reduced intensity conditioning, and were treated with chemotherapy +/− radiotherapy alone. The groups were equivalent in age (median- A 31yrs [20–51]; B 29yrs [13–47] ), disease subtype ( & gt;85% nodular sclerosing both groups), time from diagnosis to autograft (median-A 18mo [7–139]; B 20mo [4–185] ), and lines of prior therapy pre-autograft (median 3 both groups). Median time from autograft to relapse for group A was 13mo (2–56) and for group B 10mo (3–40), and patients were only selected for inclusion in group B if they responded to further salvage therapy, attained at least a stable response to treatment, and lived for & gt;12 months following relapse (median time from relapse to allogeneic transplant for group A is & lt;12 months). In this way, it was intended to include only those patients who would have been eligible for reduced intensity allogeneic transplantation had this been available at the time. Indeed, the entry criteria for group A were arguably less stringent, as patients with chemorefractory disease were included (n=14, 37%). Overall survival from diagnosis was significantly better in group A, with actuarial survival at 10yrs of 48% compared to 15% in group B (p=0.0014), and overall survival from autograft was 65% at 5 yrs in group A and 15% in group B (p= & lt;0.0001). Of group B patients treated with chemotherapy/RT alone, only 2/34 patients remain alive at a median follow-up of 22 months from relapse, one of whom has progressive disease. For group A receiving reduced intensity transplantation, actuarial survival from the time of allograft was 50% at 5 yrs. In the chemoresponsive patients, OS at 5yrs was 57% at 5 yrs with current progression-free survival of 39% at 5 yrs. This demonstration of the potential efficacy of reduced intensity transplantation in a group of heavily pre-treated patients who have failed autograft and whose outlook is otherwise extremely poor, strongly suggests further studies of reduced intensity allogeneic transplantation in Hodgkin’s Lymphoma are warranted.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 115, No. 14 ( 2010-04-08), p. 2763-2768
    Abstract: Allogeneic stem cell transplantation (SCT) is an established therapy for patients with relapsed lymphoma, but the role of positron emission tomography (PET) scanning preallogeneic and postallogeneic SCT is uncertain. We investigated whether pretransplantation PET status predicted outcome after allogeneic SCT and whether PET surveillance after transplantation provided additional information compared with computed tomography (CT) scanning. Eighty consecutive patients with lymphoma who received a reduced-intensity allogeneic SCT were entered onto a prospective trial. PET and CT scans were performed before transplantation and up to 36 months after transplantation. Forty-two patients were PET-positive before transplantation. Pretransplantation PET status had no significant impact on either relapse rate or overall survival. Thirty-four relapses were observed, of which 17 were PET-positive with a normal CT scan at relapse. Donor lymphocyte infusion (DLI) was administered in 26 episodes of relapse and was guided by PET alone in 14 patients. These findings suggest that, in contrast to autologous SCT, pretransplantation PET status is not predictive of relapse and survival after allogeneic SCT for lymphoma. Posttransplantation surveillance by PET detected relapse before CT in half of episodes, often allowing earlier administration of DLI in patients with recurrent lymphoma, and permitted withholding of potentially harmful DLI in those with PET-negative masses on CT scans.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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    detail.hit.zdb_id: 80069-7
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 8 ( 2011-03-10), p. 971-978
    Abstract: Reduced-intensity conditioning has minimized nonrelapse-related mortality rates after allogeneic transplantation in patients with Hodgkin's lymphoma, and relapse has now become the major cause for treatment failure. We aimed to assess the impact of donor lymphocyte infusions (DLIs) on relapse incidence when administered for mixed chimerism and their utility as salvage therapy when given for relapse. Patients and Methods This study reports the outcomes of 76 consecutive patients with multiply relapsed or refractory Hodgkin's lymphoma who underwent allogeneic transplantation that incorporated in vivo T-cell depletion. Forty-two patients had related donors and 34 had unrelated donors. DLIs were administered in a dose-escalating fashion to 22 patients for mixed chimerism (median time of first dose, 9 months post-transplantation) and to 24 patients for relapse. Results Three-year donor lymphocyte–related mortality was 7%, relating mainly to the induction of graft-versus-host disease. Nineteen (86%) of 22 patients receiving donor lymphocytes for mixed chimerism converted to full donor status. Four-year relapse incidence was 5% in these 22 patients compared with 43% in patients who remained relapse free but full donor chimeras at 9 months post-transplantation (P = .0071). Nineteen (79%) of 24 patients receiving donor lymphocytes for relapse responded (14 complete responses, five partial responses). Four-year overall survival from relapse was 59% in recipients of donor lymphocytes, contributing to a 4-year overall survival from transplantation of 64% and a 4-year current progression-free survival of 59% in all 76 patients. Conclusion These data demonstrate the potential for allogeneic immunotherapy with donor lymphocytes both to reduce relapse risk and to induce durable antitumor responses in patients with Hodgkin's lymphoma after hematopoietic stem-cell transplantation that incorporates in vivo T-cell depletion.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 9, No. 4 ( 2003-04), p. 257-265
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2003
    detail.hit.zdb_id: 3056525-X
    detail.hit.zdb_id: 2057605-5
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