Prognostic role of PET scanning before and after reduced-intensity allogeneic stem cell transplantation for lymphoma

Lambert, Jonathan; Bomanji, Jamshed; Peggs, Karl S.; Thomson, Kirsty; Chakraverty, Ronjon; Fielding, Adele K.; Kottaridis, Panagiotis D.; Roughton, Michael; Morris, Emma; Goldstone, Anthony H.; Linch, David C.; Ell, Peter J.; Mackinnon, Stephen

doi:10.1182/blood-2009-11-255182

Cited by 54 publications

(48 citation statements)

References 21 publications

(25 reference statements)

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“…Although a positive PET/CT scan immediately before the high-dose chemotherapy does predict a lower likelihood of cure, at least 7%-56% of patients with a positive scan remain free of subsequent relapse in the studies that have been reported. [32][33][34][35][36][37] With no alternative reliably curative treatment available, it would not be prudent to abandon high-dose chemotherapy for these patients. Whether a strategy of turning to a different potentially non-cross-resistant chemotherapy regimen in another attempt to induce a negative PET/CT scan will lead to improved outcomes is untested.…”

Section: Monitoring For Evidence Of Relapse After Completion Of Plannmentioning

confidence: 99%

Positron Emission Tomography in the Management of Hodgkin Lymphoma

Connors

2011

Hematology

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Accurate imaging of lymphoma is essential for optimal management. Positron emission tomography (PET), by providing both anatomic and functional information, is fundamentally altering staging, monitoring of response, response assessment, and choice of treatment modality for lymphomas, including Hodgkin lymphoma. This imaging technique, when used carefully in conjunction with standard testing, increases the sensitivity of lesion detection, provides an opportunity to monitor the quality of response during treatment, permits separation of fibronecrotic scar tissue from viable tumor, and adds prognostic information. PET has become integral to modern lymphoma management, but as a relatively new diagnostic technique, it is still being studied and neither its full potential nor its major limitations are fully understood. Discussed herein are recent observations from clinical trials and single-center experiences with PET to explore its advantages and limitations from a clinician's point of view.

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Section: Monitoring For Evidence Of Relapse After Completion Of Plannmentioning

confidence: 99%

Positron Emission Tomography in the Management of Hodgkin Lymphoma

Connors

2011

Hematology

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“…[1][2][3][4] However, the risk of progressive disease or relapse is considerably greater if the recipient is in partial remission at the time of transplantation or if mixed rather than complete chimerism develops when nonmyeloablative conditioning is used. [5][6][7][8] The goal of the current study was to identify a freshly isolated subset of donor T cells with potent antilymphoma activity that could promote complete chimerism without inducing severe graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) in mice.…”

Section: Introductionmentioning

confidence: 99%

CD8+CD44hi but not CD4+CD44hi memory T cells mediate potent graft antilymphoma activity without GVHD

Dutt¹,

Baker²,

Kohrt³

et al. 2011

Blood

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Allogeneic hematopoietic cell transplantation can be curative in patients with leukemia and lymphoma. However, progressive growth of malignant cells, relapse after transplantation, and graft-versushost disease (GVHD) remain important problems. The goal of the current murine study was to select a freshly isolated donor T-cell subset for infusion that separates antilymphoma activity from GVHD, and to determine whether the selected subset could effectively prevent or treat progressive growth of a naturally occurring B-cell lymphoma (BCL 1 ) without GVHD after recipients were given T cell-depleted bone marrow transplantations from major histocompatibility complex-mismatched donors. Lethal GVHD was observed when total T cells, naive CD4 ؉ T cells, or naive CD8 ؉ T cells were used. Memory CD4 ؉ CD44 hi and CD8 ؉ CD44 hi T cells containing both central and effector memory cells did not induce lethal GVHD, but only memory CD8 ؉ T cells had potent antilymphoma activity and promoted complete chimerism. Infusion of CD8 ؉ memory T cells after transplantation was able to eradicate the BCL 1 lymphoma even after progressive growth without inducing severe GVHD. In conclusion, the memory CD8 ؉ T-cell subset separated graft antilymphoma activity from GVHD more effectively than naive T cells, memory CD4 ؉ T cells, or memory total T cells. (Blood. 2011;117(11):3230-3239)

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“…Furthermore, early interventions with therapeutic DLI directed by serial flurodeoxyglucose positron emission tomographic imaging are also linked with long-term disease control (Lambert et al, 2010). In these settings, directed delivery of pre-emptive or therapeutic DLI is associated with a low incidence of GVHD (Lambert et al, 2010;Thomson et al, 2010;Peggs et al, 2011).…”

mentioning

confidence: 99%

Risk‐stratified adoptive cellular therapy following allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukaemia

et al. 2013

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SummaryFollowing reduced intensity-conditioned allogeneic stem cell transplantation (RIC allo-SCT) for chronic lymphocytic leukaemia (CLL), there is an inverse relationship between relapse and extensive chronic graft-versus-host disease (GVHD). We evaluated outcomes in 50 consecutive patients with CLL using the approach of alemtuzumab-based RIC allo-SCT and preemptive donor lymphocyte infusions (DLI) for mixed chimerism or minimal residual disease (MRD), with the intention of reducing the risk of GVHD. Forty two patients had high-risk disease, including 30% with 17p deletion (17pÀ). Of patients who were not in complete remission (CR) entering transplant, 83% subsequently achieved MRD-negative CR. Both MRD detection and uncorrected mixed chimerism were associated with greater risks of treatment failure. Nine of sixteen patients receiving DLI for persistent or relapsed disease subsequently attained MRD-negative CR. With a median follow-up of 4Á3 years, 4-year current progression-free survival was 65% and overall survival was 75% (60% and 61% in respectively, patients with 17pÀ). DLI was associated with a 29% cumulative incidence of severe GVHD and mortality of 6Á4%. At last follow-up, 83% of patients in CR were off all immunosuppressive treatment. In conclusion, the directed delivery of allogeneic cellular therapy has the potential to induce durable remissions in high-risk CLL without incurring excessive GVHD.

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Prognostic role of PET scanning before and after reduced-intensity allogeneic stem cell transplantation for lymphoma

Cited by 54 publications

References 21 publications

Positron Emission Tomography in the Management of Hodgkin Lymphoma

Positron Emission Tomography in the Management of Hodgkin Lymphoma

CD8+CD44hi but not CD4+CD44hi memory T cells mediate potent graft antilymphoma activity without GVHD

Risk‐stratified adoptive cellular therapy following allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukaemia

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