Bone Marrow Transplantation in Leukemia

Pa, Rowlings; Rp, Gale; Horowitz, M.; Bortin, Mortimer M.

doi:10.1089/scd.1.1994.3.235

Cited by 5 publications

(1 citation statement)

References 16 publications

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“…Allogeneic immune responses that drive GVHD, which may not be directed specifically at tumor or tumor tissue-derived antigens, may nonetheless heighten overall immunity by increasing chemokine or cytokine expression [231], thereby indirectly driving GVT [232]. This mechanism is supported by the clinical observation that GVT often occurs in the setting of GVHD [233, 234]. Therefore, rather than excluding GVHD patients from clinical vaccine trials, the heightened immunity from low-grade GVHD might produce a more favorable milieu for eliciting GVT by vaccination in patients that don’t require steroids, for example.…”

Section: The Role Of Vaccination In the Prevention Of Relapsementioning

confidence: 99%

NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies

Alyea

DeAngelo

Moldrem

et al. 2010

Biology of Blood and Marrow Transplantation

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Prevention of relapse after allogeneic hematopoietic stem cell transplantation is the most likely approach to improve survival of patients treated for hematologic malignancies. Herein we review the limits of currently available transplant therapies and the innovative strategies being developed to overcome resistance to therapy or to fill therapeutic modalities not currently available. These novel strategies include nonimmunologic therapies, such as targeted preparative regimens and posttransplant drug therapy, as well as immunologic interventions, including graft engineering, donor lymphocyte infusions, T cell engineering, vaccination and dendritic cell-based approaches. Several aspects of the biology of the malignant cells as well as the host have been identified that obviate success of even these newer strategies. To maximize the potential for success, we recommend pursuing research to develop additional targeted therapies to be used in the preparative regimen or as maintenance post-transplant, better characterize the T-cell and dendritic cells subsets involved in graft-versus-host disease and the graft-versus-leukemia/tumor effect, identify strategies for timing immunologic or nonimmunologic therapies to eliminate the noncycling cancer stem cell, identify more targets for immunotherapies, develop new vaccines that will not be limited by HLA, and develop methods to identify population at very high risk for relapse in order to accelerate clinical development and avoid toxicity in patients not at risk for relapse.

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Section: The Role Of Vaccination In the Prevention Of Relapsementioning

confidence: 99%

NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies

Alyea

DeAngelo

Moldrem

et al. 2010

Biology of Blood and Marrow Transplantation

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Autologous bone marrow transplantation for high risk acute lymphoblastic leukemia: clinical relevance of ex vivo bone marrow purging with monoclonal antibodies and complement

Grañena

Castellsagué

Badell

et al. 1999

Bone Marrow Transplant

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Summary:Herein we describe our experience with 75 consecutive autologous BM transplants for patients with high-risk ALL, with special attention to the clinical impact of BM purging. Fifty-two patients received purged BM using monoclonal antibody (MoAb) cocktails and complement, and 23 patients received untreated BM. The distribution of prognostic factors was similar in both groups. Hemopoietic reconstitution was adequate and did not differ in the two groups. Transplant-related mortality was 9.6% and 13% in 'purged' and 'unpurged' groups. Median follow up was 11 months (2-71) and overall actuarial probability of disease-free survival (DFS) at 5 years was 40% (53% relapse probability). We found a beneficial effect of purging in patients over 15 years of age and in patients needing more than 1 month to reach CR1. Patients in CR1 receiving purged marrow had a longer DFS and a lower relapse probability (52% vs 12%, P = 0.02 and 35% vs 86%, P = 0.005, respectively) which were related to the efficacy of the purging procedure (more or less than one log of depletion). In further CR, no advantage of purging has been found. Our data strongly suggest the clinical relevance of BM purging in autologous BMT in high-risk ALL patients and support the need for prospective randomized studies. Keywords: autologous BMT; acute lymphocytic leukemia; bone marrow purging Therapy for acute leukemia has become more and more efficient during the past decade. Most children with acute lymphoblastic leukemia (ALL) can be cured with current chemotherapy strategies. 1-3 Similarly, the majority of patients with acute myeloid leukemia (AML), regardless of their age, can achieve a complete remission (CR) using combined chemotherapy with anthracyclines, cytosine arab- inoside, etoposide, carboplatinum and other drugs in different combinations. [4][5][6] However, many of these AML patients and high-risk ALL patients will never be cured with chemotherapy due to the high incidence of relapse. 5,6 Bone marrow transplantation (BMT) technologies have improved significantly over the past 15-20 years and now constitute a regular therapeutic approach for poor-risk ALL patients. 7,8 Although allogeneic BMT is currently curative for approximately 50% of the patients, [8][9][10][11][12] unfortunately, this kind of transplant can only be applied to those patients having an HLA-identical donor, either family related or unrelated. The probability of finding an HLA-matched donor in a family with at least two children is 25-30%, and unrelated donors can be found for 50% of patients who do not have a family donor. Also the probability of being in CR rapidly decreases during the first 4 to 5 months, which is the median time necessary for a successful search for an unrelated donor. Thus 40-50% of patients will not be eligible for this potentially curative therapeutic option.Autologous BMT is an alternative to allogeneic BMT for many of these patients. 13,14 There are at least two factors that make autologous BMT less likely to be curative when compared to allogeneic t...

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Use of Partially Mismatched Related Donors Extends Access to Allogeneic Marrow Transplant

Henslee‐Downey

Abhyankar

Parrish

et al. 1997

Blood

196

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Most patients requiring allogeneic bone marrow transplant (allo-BMT) do not have an HLA-matched sibling donor. A phenotypically matched unrelated donor graft has been made available for approximately 50% of Caucasians and less than 10% of ethnic and racial minorities in need. However, almost all patients have a readily available partially mismatched related donor (PMRD). We summarize our experience with 72 patients who ranged from 1 to 50 years of age (median, 16 years) and who were recipients of a PMRD allo-BMT from haploidentical family members following conditioning therapy using total body irradiation (TBI) and multiagent, high-dose chemotherapy. T-cell depletion and post-BMT immunosuppression were combined for graft-versus-host disease (GVHD) prophylaxis. The probability of engraftment was 0.88 at 32 days. Six of 10 patients who failed to engraft achieved engraftment after secondary transplant. Grade II to IV acute GVHD was seen in 9 of 58 (16%) evaluable patients; extensive chronic GVHD was seen in 4 of 48 (8%) evaluable patients. There was a statistically significant difference in 2-year survival probability between low-risk and high-risk patients (0.55 v 0.27, P = .048). Prognostic factors that affected outcomes in multivariate analysis were (1) a lower TBI dose and 3-antigen rejection mismatch decreased stable engraftment (P = .005 and P = .002, respectively); (2) a higher T-cell dose increased acute GVHD (P = .058); (3) a higher TBI dose increased chronic GVHD (P = .016); and (4) a high-risk disease category increased treatment failure from relapse or death (P = .037). A PMRD transplant can be performed with acceptable rates of graft failure and GVHD. Using sequential immunomodulation, the disease status at the time of transplant is the only prognostic factor significantly associated with long-term successful outcome after PMRD allo-BMT. When allogeneic rather than autologous BMT is indicated, progression in disease status before transplant can be avoided using a PMRD with equal inclusion of all ethnic or racial groups.

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Bone Marrow Transplantation in Leukemia

Cited by 5 publications

References 16 publications

NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies

NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies

Autologous bone marrow transplantation for high risk acute lymphoblastic leukemia: clinical relevance of ex vivo bone marrow purging with monoclonal antibodies and complement

Use of Partially Mismatched Related Donors Extends Access to Allogeneic Marrow Transplant

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