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  • American Society of Hematology  (25)
  • 1
    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
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    In: Blood, American Society of Hematology, Vol. 96, No. 7 ( 2000-10-01), p. 2419-2425
    Abstract: A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days −8 to −4; fludarabine, 30 mg/m2 on days −7 to −3; and melphalan, 140 mg/m2 on day −2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor–mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2000
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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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
    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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  • 4
    In: Blood, American Society of Hematology, Vol. 96, No. 7 ( 2000-10-01), p. 2419-2425
    Abstract: A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days −8 to −4; fludarabine, 30 mg/m2 on days −7 to −3; and melphalan, 140 mg/m2 on day −2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor–mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2000
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    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
    detail.hit.zdb_id: 1468538-3
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  • 6
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 146-146
    Abstract: Abstract 146 Transplant-related complications necessitate intensive care unit (ICU) admission in a significant proportion of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Historically patients requiring ICU admission for transplant related toxicities have fared extremely poorly with very high ICU mortality rates. Although recent reports have indicated improvements in short-term survival for Allo-HSCT patients admitted to ICU there are little data on the subsequent long-term survival of ICU survivors and the impact of reduced intensity conditioning regimens in this cohort of patients. Methods: A retrospective analysis of data collected from 164 consecutive adult Allo-HSCT recipients admitted to ICU (with a total of 214 ICU admissions), at a single centre, University College London Hospitals NHS Foundation Trust (UCLH) between June 1996 and December 2007 (11.5 year study period) was performed. Follow-up of surviving patients was recorded until 31 March 2011. Results: 29% of all patients undergoing Allo-HSCT at our centre during the study period required one or more ICU admission. The ICU admission rate was significantly lower for patients undergoing reduced intensity conditioning (RIC) than myeloablative conditioning (17% vs. 38%, p 〈 0.001). The median age of RIC-Allo recipients was significantly older than patients who received myeloablative conditioning (47 vs 36 years, P 〈 0.0001). The most frequent reasons for ICU admission were sepsis (67%) and respiratory failure (55%), not mutually exclusive. Mechanical ventilation (MV) was required in 53% of admissions, inotropic support was required in 47%. Median acute physiology and chronic health score (APACHEII) was 23 (range 0–51). Overall ICU survival for all admissions was 48% (n=214). 35 patients (21%) had more 1 or more ICU admissions. Survival by patient (measured at discharge from final ICU admission) was 32%. ICU survival was significantly better after RIC Allo-HSCT than following myeloablative conditioning (OR 3.27, p=0.023). There was no difference in ICU outcome by stem cell source (sibling vs. unrelated). Patients who did not require ventilatory support (non-invasive ventilation and/or MV) had significantly better ICU outcome (OR 12.7, p 〈 0.001). Multivariate analysis by Cox regression revealed raised urea, inotropic support and MV as independent determinants of death on ICU. Long term survival was significantly better for patients who underwent RIC Allo-HSCT (p=0.0055) (Figure 1). The subsequent long term survival for patients who survived ICU admission was excellent; 1, 2, and 5 year survival rates were 60%, 55%, and 50% respectively (median follow-up 3 years, 7 months).A simple prognostic scoring system has been derived which is predictive of both ICU survival and long term outcome (Table 1). Patients with 2 or more of the following factors: myeloablative conditioning, MV, elevated serum urea, score 1. Patients with 〈 2 of these factors score 0. In our patient population, this binary index has been shown to be predictive of both death on ICU (OR 7.24, p=0.001) or poorer overall survival after ICU discharge (OR 3.04, p=0.01). Conclusion: In this study we report favourable ICU survival following allogeneic HSCT and for the first time report significantly better short and long-term outcome for patients who underwent RIC Allo-HSCT compared to those treated with myeolablative conditioning regimens despite a higher median age in the patients undergoing RIC transplants. For patients surviving ICU admission, subsequent long-term overall survival was excellent at 50% at 5 years, comparing favourably with other critically ill non-surgical patients admitted to ICU. A simple prognostic score has been generated which can be used to predict outcome in critically ill patients admitted to ICU following Allo-HSCT. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 98, No. 6 ( 2001-09-15), p. 1752-1759
    Abstract: In acute myeloid leukemia (AML), further prognostic determinants are required in addition to cytogenetics to predict patients at increased risk of relapse. Recent studies have indicated that an internal tandem duplication (ITD) in the FLT3 gene may adversely affect clinical outcome. This study evaluated the impact of a FLT3/ITD mutation on outcome in 854 patients, mostly 60 years of age or younger, treated in the United Kingdom Medical Research Council (MRC) AML trials. An FLT3/ITD mutation was present in 27% of the patients and was associated with leukocytosis and a high percentage of bone marrow blast cells (P  & lt; .001 for both). It had a borderline association with a lower complete remission rate (P = .05) and a higher induction death rate (P = .04), and was associated with increased relapse risk (RR), adverse disease-free survival (DFS), event-free survival (EFS), and overall survival (OS) (P  & lt; .001 for all). In multivariate analysis, presence of a mutation was the most significant prognostic factor predicting RR and DFS (P  & lt; .0001) and was still significant for OS (P = .009) and EFS (P = .002). There was no evidence that the relative effect of a FLT3/ITD differed between the cytogenetic risk groups. More than one mutation was detected in 23% of FLT3/ITD+ patients and was associated with worse OS (P = .04) and EFS (P = .07). Biallelic disease or partial/complete loss of wild-type alleles was present in 10% of FLT3/ITD+ patients. The suggestion is made that detection of a FLT3/ITD should be included as a routine test at diagnosis and evaluated for therapeutic management.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2001
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    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
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  • 9
    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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  • 10
    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:
    RVK:
    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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