Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions

Schaap, Nicolaas; Schattenberg, A.V.M.B.; Bär, B.M.A.M.; Preijers, Frank; Kemenade, E van de Wiel van; Witte, Théo de

doi:10.1038/sj.leu.2402203

Cited by 54 publications

(45 citation statements)

References 48 publications

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“…This has been implemented with some success, particularly in high-risk patients treated with T-cell depleted (TCD) conditioning regimens. [31][32][33][34][35] Immunosuppressant therapy is tapered rapidly and DLI commenced early (1-6 months) and then stopped when a degree of GvHD is present or when a set cell dose is reached.…”

Section: Predicting and Preventing Relapsementioning

confidence: 99%

“…The group included adults and children and the donor was an HLA-identical sibling in 24, unrelated donor in 14 (3 mismatched) and 1 was a mismatched relative. The majority 34 received a myeloablative transplant as the first procedure, 59% including TCD in the protocol. The second allograft was performed using fludarabine-based RIC in most cases.…”

Section: Donor Leucocyte Infusionsmentioning

confidence: 99%

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Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant

Shaw

Russell

2007

Bone Marrow Transplant

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Section: Predicting and Preventing Relapsementioning

confidence: 99%

Section: Donor Leucocyte Infusionsmentioning

confidence: 99%

Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant

Shaw

Russell

2007

Bone Marrow Transplant

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“…The relatively good results of allogeneic BMT (matched related and MUD) compared with conventional chemotherapy are because of the existence of graft-versusleukemia (GVL) effect, 21,22 in addition to the myeloablation obtained with high-dose radio-chemotherapy. Ph+ ALL patients should therefore be considered for allogeneic stem cell transplantation in first CR.…”

Section: Mud Transplantationmentioning

confidence: 99%

“…Several reports have shown a strong association between the existence of post-transplant GVHD and a lower relapse risk 22,64 Therefore, donor lymphocyte infusion has been suggested to augment this antileukemic effect even further. 21,65 Although response following DLI in patients with relapsed ALL is considered to be disappointing, [66][67][68] some recent publications suggest DLI to be effective in some of the patients. 21,65 Schaap et al 21 reported a significant reduction in relapse rate in ALL patients who had an allogeneic BMT followed by pre-emptive DLI therapy.…”

Section: Donor Lymphocyte Infusionmentioning

confidence: 99%

Bone marrow transplant in Ph+ ALL patients

Avivi

Goldstone

2003

Bone Marrow Transplant

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Summary:Although the outcome for Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) with conventional chemotherapy is poor, the outcome after a siblingmatched allogeneic bone marrow transplantation (BMT) seems to be significantly better. The surprising success of allogeneic BMT may be because of disease response to high-dose chemotherapy combined with a graft-versusleukemia effect. However, less than 30% of patients have a matched related donor available, and some of them will be too old/not fit for conventional BMT. While young patients who do not have a matched related donor should be considered for matched unrelated donor (MUD) transplant, older patients may be treated with autologous stem cell transplantation (ASCT) or rarely considered for a low-intensity MUD transplant. The efficacy of autologous BMT compared with chemotherapy is still debatable, although the new tyrosine kinase inhibitor Imatinib may be used for pretransplant purging/posttransplant therapy, aiming to improve autologous and allogeneic BMT results. The advantage of low-intensity sib/MUD allograft compared with chemotherapy is not proven either and is currently under investigation. However, if shown to be curative, low-intensity allograft may significantly improve the outcome of older Ph+ ALL patients, who are not eligible for conventional allograft. Bone Marrow Transplantation (2003Transplantation ( ) 31, 623-632. doi:10.1038 Keywords: autologous; allogeneic bone marrow transplantation; Ph+ ALL The Philadelphia chromosome (Ph) represents the most common cytogenetic abnormality in adult acute lymphoblastic leukemia (ALL). It occurs in fewer than 5% of ALL cases in children, but in around 20-30% of cases in adults, with an increasing incidence with age.

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“…8,9 This approach appears to be effective for patients with CML 10 and may also have a role for patients with acute leukemia. 11 In one trial that included 82 patients with a variety of diseases, pre-emptive DLI resulted in improved 3-year DFS though was complicated by unacceptable GVHD when given at 0.7 Â 10 8 CD3 cells/kg; only eight of 25 patients who received 0.1 m Â 10 8 CD3 cells/kg developed grade I-II acute GVHD. 11 In CML, other successful approaches to minimize GVHD have included the use of low-dose DLI with gradual dose escalation, 12 depletion of CD8-positive cells from the donor product, 13,14 and the use of irradiated (and hence inactivated) DLI.…”

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confidence: 99%

Donor leukocyte infusions in acute myelogenous leukemia

Porter

2003

Leukemia

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The success of allogeneic stem cell transplantation (SCT) is dependent not only on the intensive conditioning therapy, but also on the graft-versus-leukemia (GVL) properties of the donor graft. Unfortunately, despite recent advances, disease relapse remains a major obstacle to successful transplant in patients with acute myeloid leukemia (AML). Patients transplanted in first remission have a 10-20% relapse rate and those with more advanced disease have relapse rates of 40-60%. The treatment options for relapse have generally been limited. Second SCT may cure a minority of these patients but at the expense of extensive morbidity and mortality. A safer and more effective approach to relapse is needed. One such approach is the use of donor leukocyte infusions (DLI) to induce a direct GVL reaction for patients with relapsed AML without the need for additional myeloablative conditioning therapy.Kolb et al 1 first published the effective use of DLI in three patients with relapsed chronic myelogenous leukemia (CML) who all had a complete cytogenetic remission. Subsequent studies have confirmed that DLI is dramatically effective for patients with CML. In all, 70-80% of chronic phase CML patients treated with DLI achieve a complete cytogenetic response, 2,3 and the majority of these patients achieve a molecular remission as well. DLI has been much less effective for patients with acute leukemia. Retrospective data, compiled from two large registries (the North American registry and the European Group for Blood and Marrow Transplantation) indicate that response rates to DLI for relapsed AML range from 15 to 30%. 2,3 Response rates in acute lymphoblastic leukemia (ALL) are even lower, at about 10%.While DLI-induced remissions are achieved in only a small number of AML patients, many of these remissions may be durable. Of 10 patients in the North American registry who had achieved a complete remission (CR) from DLI, only two subsequently relapsed at 1-3 years. At a median follow-up of 1 year, five patients were alive and in CR. The two that relapsed died of disease and three other patients had died of treatmentrelated causes. 4 The effects of DLI appear to be similar in patients receiving unrelated donor transplants, although only small numbers of recipients of unrelated DLI (UDLI) have been reported. In collaboration with the National Marrow Donor Program, we retrospectively identified 23 AML patients who received UDLI for relapsed AML. 5 The median follow-up was 10 weeks (range 4-102 weeks). Of the patients evaluable for response to DLI alone, 42% achieved a CR. However, only 4/23 of all patients (17%) had a durable CR. From this study and others, it is clear that the most significant predictor of survival and disease-free survival (DFS) was the time from transplant to relapse. 6 Of interest, there was no dose-response effect identified in the unrelated donor setting though the majority of patients received more than 1 Â 10 7 mononuclear cells/kg.Although a minority of patients will achieve a durable CR after DLI, one fac...

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Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions

Cited by 54 publications

References 48 publications

Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant

Treatment options for the management of acute leukaemia relapsing following an allogeneic transplant

Bone marrow transplant in Ph+ ALL patients

Donor leukocyte infusions in acute myelogenous leukemia

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