T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma

Kirsty J. Thomson; Emma C. Morris; Don Milligan; Anne N. Parker; Ann E. Hunter; Gordon Cook; Adrian J. C. Bloor; Fiona Clark; Majid Kazmi; David C. Linch; Ronjon Chakraverty; Karl S. Peggs; Stephen Mackinnon

doi:10.1200/JCO.2009.26.9100

T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma

Kirsty J. Thomson^*, Emma C. Morris, Don Milligan, Anne N. Parker, Ann E. Hunter, Gordon Cook, Adrian J. C. Bloor, Fiona Clark, Majid Kazmi, David C. Linch, Ronjon Chakraverty, Karl S. Peggs, Stephen Mackinnon

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

124 Citations (Scopus)

Abstract

Purpose

Follicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored.

Patients and Methods

This study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors.

Results

With a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors).

Conclusion

The excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.

Original language	English
Pages (from-to)	3695-3700
Number of pages	6
Journal	Journal of Clinical Oncology
Volume	28
Issue number	23
DOIs	https://doi.org/10.1200/JCO.2009.26.9100
Publication status	Published - 10 Aug 2010

Keywords

BONE-MARROW-TRANSPLANTATION
NON-HODGKINS-LYMPHOMA
ALLOGENEIC HEMATOPOIETIC TRANSPLANTATION
CHRONIC LYMPHOCYTIC-LEUKEMIA
LOW-GRADE LYMPHOMA
AUTOLOGOUS TRANSPLANTATION
ADOPTIVE IMMUNOTHERAPY
HOST-DISEASE
TOXICITY
MORTALITY

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Thomson, K. J., Morris, E. C., Milligan, D., Parker, A. N., Hunter, A. E., Cook, G., Bloor, A. J. C., Clark, F., Kazmi, M., Linch, D. C., Chakraverty, R., Peggs, K. S., & Mackinnon, S. (2010). T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma. Journal of Clinical Oncology, 28(23), 3695-3700. https://doi.org/10.1200/JCO.2009.26.9100

@article{0219294e43ee48e19541c8ef15171c8d,

title = "T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma",

abstract = "PurposeFollicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored.Patients and MethodsThis study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors.ResultsWith a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors).ConclusionThe excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.",

keywords = "BONE-MARROW-TRANSPLANTATION, NON-HODGKINS-LYMPHOMA, ALLOGENEIC HEMATOPOIETIC TRANSPLANTATION, CHRONIC LYMPHOCYTIC-LEUKEMIA, LOW-GRADE LYMPHOMA, AUTOLOGOUS TRANSPLANTATION, ADOPTIVE IMMUNOTHERAPY, HOST-DISEASE, TOXICITY, MORTALITY",

author = "Thomson, {Kirsty J.} and Morris, {Emma C.} and Don Milligan and Parker, {Anne N.} and Hunter, {Ann E.} and Gordon Cook and Bloor, {Adrian J. C.} and Fiona Clark and Majid Kazmi and Linch, {David C.} and Ronjon Chakraverty and Peggs, {Karl S.} and Stephen Mackinnon",

year = "2010",

month = aug,

day = "10",

doi = "10.1200/JCO.2009.26.9100",

language = "English",

volume = "28",

pages = "3695--3700",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "23",

}

Thomson, KJ, Morris, EC, Milligan, D, Parker, AN, Hunter, AE, Cook, G, Bloor, AJC, Clark, F, Kazmi, M, Linch, DC, Chakraverty, R, Peggs, KS & Mackinnon, S 2010, 'T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma', Journal of Clinical Oncology, vol. 28, no. 23, pp. 3695-3700. https://doi.org/10.1200/JCO.2009.26.9100

T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma. / Thomson, Kirsty J.; Morris, Emma C.; Milligan, Don et al.
In: Journal of Clinical Oncology, Vol. 28, No. 23, 10.08.2010, p. 3695-3700.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma

AU - Thomson, Kirsty J.

AU - Morris, Emma C.

AU - Milligan, Don

AU - Parker, Anne N.

AU - Hunter, Ann E.

AU - Cook, Gordon

AU - Bloor, Adrian J. C.

AU - Clark, Fiona

AU - Kazmi, Majid

AU - Linch, David C.

AU - Chakraverty, Ronjon

AU - Peggs, Karl S.

AU - Mackinnon, Stephen

PY - 2010/8/10

Y1 - 2010/8/10

N2 - PurposeFollicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored.Patients and MethodsThis study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors.ResultsWith a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors).ConclusionThe excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.

AB - PurposeFollicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored.Patients and MethodsThis study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors.ResultsWith a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors).ConclusionThe excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.

KW - BONE-MARROW-TRANSPLANTATION

KW - NON-HODGKINS-LYMPHOMA

KW - ALLOGENEIC HEMATOPOIETIC TRANSPLANTATION

KW - CHRONIC LYMPHOCYTIC-LEUKEMIA

KW - LOW-GRADE LYMPHOMA

KW - AUTOLOGOUS TRANSPLANTATION

KW - ADOPTIVE IMMUNOTHERAPY

KW - HOST-DISEASE

KW - TOXICITY

KW - MORTALITY

U2 - 10.1200/JCO.2009.26.9100

DO - 10.1200/JCO.2009.26.9100

M3 - Article

SN - 0732-183X

VL - 28

SP - 3695

EP - 3700

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 23

ER -

Thomson KJ, Morris EC, Milligan D, Parker AN, Hunter AE, Cook G et al. T-Cell-Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma. Journal of Clinical Oncology. 2010 Aug 10;28(23):3695-3700. doi: 10.1200/JCO.2009.26.9100