Outcome of Donor Lymphocyte Infusion after T Cell-depleted Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes

Pramila Krishnamurthy; Victoria T Potter; Linda D Barber; Austin G Kulasekararaj; Zi Yi Lim; Rachel M Pearce; Hugues de Lavallade; Michelle Kenyon; Robin Ireland; Judith C W Marsh; Stephen Devereux; Antonio Pagliuca; Ghulam J Mufti

doi:10.1016/j.bbmt.2012.12.013

Outcome of Donor Lymphocyte Infusion after T Cell-depleted Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes

Pramila Krishnamurthy, Victoria T Potter, Linda D Barber, Austin G Kulasekararaj, Zi Yi Lim, Rachel M Pearce, Hugues de Lavallade, Michelle Kenyon, Robin Ireland, Judith C W Marsh, Stephen Devereux, Antonio Pagliuca, Ghulam J Mufti

King's College London

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

75 Citations (Scopus)

Abstract

Relapse occurs in 30%-50% of recipients of T cell-depleted (TCD) reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Despite limited published supportive data, donor lymphocyte infusion (DLI) is used preemptively (pDLI) to improve donor chimerism and prevent relapse, and therapeutically (tDLI) after disease recurrence. We evaluated the efficacy and toxicity of pDLI and tDLI in 113 patients after TCD (alemtuzumab, n = 99; antithymocyte globulin, n = 14) RIC HSCT for AML or MDS. Recipients of pDLI (n = 62) had an estimated 5-year overall survival (OS) of 80% and an event-free survival of 65%. More than one-half (52%; n = 32) of the patients received pDLI within 6 months post-HSCT; despite this, the 5-year incidence of graft-versus-host disease was only 31% (95% confidence interval [CI], 19%-43%). Recipients of tDLI (n = 51) had an estimated 5-year OS of 40% and a 5-year relapse/progression rate of 69% (95% CI, 54%-81%). Recipients of tDLI at >6 months post-HSCT had a significantly superior 5-year OS after tDLI compared with those treated earlier (P = .008). The cumulative incidence of graft-versus-host disease at 5 years after tDLI was 45% (95% CI, 23%-65%). We demonstrate that pDLI safely promotes durable remission after TCD RIC HSCT for AML or MDS, and that tDLI salvages patients after late relapse with greater efficacy.

Original language	English
Pages (from-to)	562-568
Number of pages	7
Journal	BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume	19
Issue number	4
DOIs	https://doi.org/10.1016/j.bbmt.2012.12.013
Publication status	Published - Apr 2013

Keywords

Adult
Aged
Antibodies, Monoclonal, Humanized
Antilymphocyte Serum
Antineoplastic Agents
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Lymphocyte Depletion
Male
Middle Aged
Myelodysplastic Syndromes
Recurrence
Survival Analysis
T-Lymphocytes
Transplantation Conditioning
Transplantation, Homologous
Treatment Outcome

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10.1016/j.bbmt.2012.12.013

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Krishnamurthy, P., Potter, V. T., Barber, L. D., Kulasekararaj, A. G., Lim, Z. Y., Pearce, R. M., de Lavallade, H., Kenyon, M., Ireland, R., Marsh, J. C. W., Devereux, S., Pagliuca, A., & Mufti, G. J. (2013). Outcome of Donor Lymphocyte Infusion after T Cell-depleted Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 19(4), 562-568. https://doi.org/10.1016/j.bbmt.2012.12.013

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title = "Outcome of Donor Lymphocyte Infusion after T Cell-depleted Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes",

abstract = "Relapse occurs in 30%-50% of recipients of T cell-depleted (TCD) reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Despite limited published supportive data, donor lymphocyte infusion (DLI) is used preemptively (pDLI) to improve donor chimerism and prevent relapse, and therapeutically (tDLI) after disease recurrence. We evaluated the efficacy and toxicity of pDLI and tDLI in 113 patients after TCD (alemtuzumab, n = 99; antithymocyte globulin, n = 14) RIC HSCT for AML or MDS. Recipients of pDLI (n = 62) had an estimated 5-year overall survival (OS) of 80% and an event-free survival of 65%. More than one-half (52%; n = 32) of the patients received pDLI within 6 months post-HSCT; despite this, the 5-year incidence of graft-versus-host disease was only 31% (95% confidence interval [CI], 19%-43%). Recipients of tDLI (n = 51) had an estimated 5-year OS of 40% and a 5-year relapse/progression rate of 69% (95% CI, 54%-81%). Recipients of tDLI at >6 months post-HSCT had a significantly superior 5-year OS after tDLI compared with those treated earlier (P = .008). The cumulative incidence of graft-versus-host disease at 5 years after tDLI was 45% (95% CI, 23%-65%). We demonstrate that pDLI safely promotes durable remission after TCD RIC HSCT for AML or MDS, and that tDLI salvages patients after late relapse with greater efficacy.",

keywords = "Adult, Aged, Antibodies, Monoclonal, Humanized, Antilymphocyte Serum, Antineoplastic Agents, Female, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute, Lymphocyte Depletion, Male, Middle Aged, Myelodysplastic Syndromes, Recurrence, Survival Analysis, T-Lymphocytes, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome",

author = "Pramila Krishnamurthy and Potter, {Victoria T} and Barber, {Linda D} and Kulasekararaj, {Austin G} and Lim, {Zi Yi} and Pearce, {Rachel M} and {de Lavallade}, Hugues and Michelle Kenyon and Robin Ireland and Marsh, {Judith C W} and Stephen Devereux and Antonio Pagliuca and Mufti, {Ghulam J}",

year = "2013",

month = apr,

doi = "10.1016/j.bbmt.2012.12.013",

language = "English",

volume = "19",

pages = "562--568",

journal = "BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION",

issn = "1083-8791",

publisher = "Elsevier Inc.",

number = "4",

}

Krishnamurthy, P , Potter, VT , Barber, LD, Kulasekararaj, AG, Lim, ZY, Pearce, RM, de Lavallade, H, Kenyon, M, Ireland, R , Marsh, JCW , Devereux, S, Pagliuca, A & Mufti, GJ 2013, 'Outcome of Donor Lymphocyte Infusion after T Cell-depleted Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes', BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, vol. 19, no. 4, pp. 562-568. https://doi.org/10.1016/j.bbmt.2012.12.013

Outcome of Donor Lymphocyte Infusion after T Cell-depleted Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes. / Krishnamurthy, Pramila ; Potter, Victoria T ; Barber, Linda D et al.
In: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, Vol. 19, No. 4, 04.2013, p. 562-568.

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

TY - JOUR

T1 - Outcome of Donor Lymphocyte Infusion after T Cell-depleted Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes

AU - Krishnamurthy, Pramila

AU - Potter, Victoria T

AU - Barber, Linda D

AU - Kulasekararaj, Austin G

AU - Lim, Zi Yi

AU - Pearce, Rachel M

AU - de Lavallade, Hugues

AU - Kenyon, Michelle

AU - Ireland, Robin

AU - Marsh, Judith C W

AU - Devereux, Stephen

AU - Pagliuca, Antonio

AU - Mufti, Ghulam J

PY - 2013/4

Y1 - 2013/4

N2 - Relapse occurs in 30%-50% of recipients of T cell-depleted (TCD) reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Despite limited published supportive data, donor lymphocyte infusion (DLI) is used preemptively (pDLI) to improve donor chimerism and prevent relapse, and therapeutically (tDLI) after disease recurrence. We evaluated the efficacy and toxicity of pDLI and tDLI in 113 patients after TCD (alemtuzumab, n = 99; antithymocyte globulin, n = 14) RIC HSCT for AML or MDS. Recipients of pDLI (n = 62) had an estimated 5-year overall survival (OS) of 80% and an event-free survival of 65%. More than one-half (52%; n = 32) of the patients received pDLI within 6 months post-HSCT; despite this, the 5-year incidence of graft-versus-host disease was only 31% (95% confidence interval [CI], 19%-43%). Recipients of tDLI (n = 51) had an estimated 5-year OS of 40% and a 5-year relapse/progression rate of 69% (95% CI, 54%-81%). Recipients of tDLI at >6 months post-HSCT had a significantly superior 5-year OS after tDLI compared with those treated earlier (P = .008). The cumulative incidence of graft-versus-host disease at 5 years after tDLI was 45% (95% CI, 23%-65%). We demonstrate that pDLI safely promotes durable remission after TCD RIC HSCT for AML or MDS, and that tDLI salvages patients after late relapse with greater efficacy.

AB - Relapse occurs in 30%-50% of recipients of T cell-depleted (TCD) reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Despite limited published supportive data, donor lymphocyte infusion (DLI) is used preemptively (pDLI) to improve donor chimerism and prevent relapse, and therapeutically (tDLI) after disease recurrence. We evaluated the efficacy and toxicity of pDLI and tDLI in 113 patients after TCD (alemtuzumab, n = 99; antithymocyte globulin, n = 14) RIC HSCT for AML or MDS. Recipients of pDLI (n = 62) had an estimated 5-year overall survival (OS) of 80% and an event-free survival of 65%. More than one-half (52%; n = 32) of the patients received pDLI within 6 months post-HSCT; despite this, the 5-year incidence of graft-versus-host disease was only 31% (95% confidence interval [CI], 19%-43%). Recipients of tDLI (n = 51) had an estimated 5-year OS of 40% and a 5-year relapse/progression rate of 69% (95% CI, 54%-81%). Recipients of tDLI at >6 months post-HSCT had a significantly superior 5-year OS after tDLI compared with those treated earlier (P = .008). The cumulative incidence of graft-versus-host disease at 5 years after tDLI was 45% (95% CI, 23%-65%). We demonstrate that pDLI safely promotes durable remission after TCD RIC HSCT for AML or MDS, and that tDLI salvages patients after late relapse with greater efficacy.

KW - Adult

KW - Aged

KW - Antibodies, Monoclonal, Humanized

KW - Antilymphocyte Serum

KW - Antineoplastic Agents

KW - Female

KW - Graft vs Host Disease

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Leukemia, Myeloid, Acute

KW - Lymphocyte Depletion

KW - Male

KW - Middle Aged

KW - Myelodysplastic Syndromes

KW - Recurrence

KW - Survival Analysis

KW - T-Lymphocytes

KW - Transplantation Conditioning

KW - Transplantation, Homologous

KW - Treatment Outcome

U2 - 10.1016/j.bbmt.2012.12.013

DO - 10.1016/j.bbmt.2012.12.013

M3 - Article

C2 - 23266740

SN - 1083-8791

VL - 19

SP - 562

EP - 568

JO - BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

JF - BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION

IS - 4

ER -

Outcome of Donor Lymphocyte Infusion after T Cell-depleted Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myelogenous Leukemia and Myelodysplastic Syndromes

Abstract

Keywords

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