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Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study

Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study
Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study

Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors. The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003. Cytogenetic data were available for 68% of the patients; of these, at diagnosis, 42% had good risk features, 57% had standard risk features, and 1% had poor risk features. Conditioning regimens varied; autologous rescue was provided with bone marrow (BM) (71%), peripheral blood stem cells (PBSCs) (18%), or both (11%), which were harvested during first complete remission (CR1) and/or second CR (CR2). Median follow-up was 84 months (range, 2-200 months). At 10 years, actuarial overall survival (OS) was 32%, progression-free survival (PFS) was 28%, and relapse rate (RR) was 57%. The 100-day nonrelapse mortality (NRM) was 7%, rising to 11% at 1 year and to 14% at 10 years. OS was significantly related to M3 subtype (5-year OS, 66%; P = .005), patient age at diagnosis (P = .005) and transplantation (P = .026), and length of CR1, with greatest significance if the patient was dichotomized at CR1 duration of < 8 months or > or = 8 months (P = .0001). There was no difference in OS between regimens containing total body irradiation (TBI) and chemotherapy alone (P = .7). In relation to the nature of autologous graft material, there was improved OS (P = .025) and PFS (P = .009) with the use of cells harvested entirely in CR1 compared with cells harvested in CR2 or in both CR1 and CR2. Engraftment times were significantly shortened with the use of PBSCs alone or in combination with BM compared with BM alone (P = .0001), but there was no significant long-term impact on OS, PFS, RR, or NRM. This study provides long-term follow-up data in one of the largest series of patients with standard-risk and good-risk AML in CR2 treated with autologous transplantation and supports earlier observations that long-term survival is achievable in about 1/3 of patients overall and in about 2/3 of patients with M3 with a relatively low NRM. Outcomes are better in patients with CR1 > or = 8 months by use of grafts obtained entirely in CR1 and use of PBSCs. TBI conditioning did not confer an advantage. Randomized studies against unrelated donor transplantation are warranted.

Acute Disease, Adolescent, Adult, Age Factors, Aged, Bone Marrow Transplantation, Busulfan, Cyclophosphamide, Etoposide, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Male, Melphalan, Middle Aged, Peripheral Blood Stem Cell Transplantation, Registries, Remission Induction, Retrospective Studies, Risk Factors, Salvage Therapy, Survival Analysis, Transplantation Conditioning, Transplantation, Autologous, United Kingdom, Whole-Body Irradiation, Journal Article, Research Support, Non-U.S. Gov't
1083-8791
1310-7
Chantry, Andrew D
0c60e4ad-911b-48b9-9e9b-c854c33498b9
Snowden, John A
42b7c449-e6c2-43e0-9a52-af0213fa7cf4
Craddock, Charles
ec80de01-977b-4d16-8538-2ad72303bd7e
Peggs, Karl
a5c55130-46df-4945-9e55-ee15b2fd2f20
Roddie, Claire
a46a9124-80ed-4c65-a7b5-9d315e30dd76
Craig, Jenny I O
39850fea-6b7d-4279-a46d-362939e0ea03
Orchard, Kim
794654ab-d6cc-488a-ac11-c9217433c7a2
Towlson, Keiren E
cf307e17-df48-42c0-923e-c5e841569083
Pearce, Rachel M
52229378-6717-4148-927d-817f72a290ab
Marks, David I
7e83726c-7b1f-4451-ad6c-a5d67c425203
BSBMT Clinical Trials Committee
Chantry, Andrew D
0c60e4ad-911b-48b9-9e9b-c854c33498b9
Snowden, John A
42b7c449-e6c2-43e0-9a52-af0213fa7cf4
Craddock, Charles
ec80de01-977b-4d16-8538-2ad72303bd7e
Peggs, Karl
a5c55130-46df-4945-9e55-ee15b2fd2f20
Roddie, Claire
a46a9124-80ed-4c65-a7b5-9d315e30dd76
Craig, Jenny I O
39850fea-6b7d-4279-a46d-362939e0ea03
Orchard, Kim
794654ab-d6cc-488a-ac11-c9217433c7a2
Towlson, Keiren E
cf307e17-df48-42c0-923e-c5e841569083
Pearce, Rachel M
52229378-6717-4148-927d-817f72a290ab
Marks, David I
7e83726c-7b1f-4451-ad6c-a5d67c425203

Chantry, Andrew D, Snowden, John A, Craddock, Charles, Peggs, Karl, Roddie, Claire, Craig, Jenny I O, Orchard, Kim, Towlson, Keiren E, Pearce, Rachel M and Marks, David I , BSBMT Clinical Trials Committee (2006) Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study. Biology of Blood and Marrow Transplantation, 12 (12), 1310-7. (doi:10.1016/j.bbmt.2006.07.015).

Record type: Article

Abstract

Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors. The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003. Cytogenetic data were available for 68% of the patients; of these, at diagnosis, 42% had good risk features, 57% had standard risk features, and 1% had poor risk features. Conditioning regimens varied; autologous rescue was provided with bone marrow (BM) (71%), peripheral blood stem cells (PBSCs) (18%), or both (11%), which were harvested during first complete remission (CR1) and/or second CR (CR2). Median follow-up was 84 months (range, 2-200 months). At 10 years, actuarial overall survival (OS) was 32%, progression-free survival (PFS) was 28%, and relapse rate (RR) was 57%. The 100-day nonrelapse mortality (NRM) was 7%, rising to 11% at 1 year and to 14% at 10 years. OS was significantly related to M3 subtype (5-year OS, 66%; P = .005), patient age at diagnosis (P = .005) and transplantation (P = .026), and length of CR1, with greatest significance if the patient was dichotomized at CR1 duration of < 8 months or > or = 8 months (P = .0001). There was no difference in OS between regimens containing total body irradiation (TBI) and chemotherapy alone (P = .7). In relation to the nature of autologous graft material, there was improved OS (P = .025) and PFS (P = .009) with the use of cells harvested entirely in CR1 compared with cells harvested in CR2 or in both CR1 and CR2. Engraftment times were significantly shortened with the use of PBSCs alone or in combination with BM compared with BM alone (P = .0001), but there was no significant long-term impact on OS, PFS, RR, or NRM. This study provides long-term follow-up data in one of the largest series of patients with standard-risk and good-risk AML in CR2 treated with autologous transplantation and supports earlier observations that long-term survival is achievable in about 1/3 of patients overall and in about 2/3 of patients with M3 with a relatively low NRM. Outcomes are better in patients with CR1 > or = 8 months by use of grafts obtained entirely in CR1 and use of PBSCs. TBI conditioning did not confer an advantage. Randomized studies against unrelated donor transplantation are warranted.

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More information

Published date: December 2006
Keywords: Acute Disease, Adolescent, Adult, Age Factors, Aged, Bone Marrow Transplantation, Busulfan, Cyclophosphamide, Etoposide, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Male, Melphalan, Middle Aged, Peripheral Blood Stem Cell Transplantation, Registries, Remission Induction, Retrospective Studies, Risk Factors, Salvage Therapy, Survival Analysis, Transplantation Conditioning, Transplantation, Autologous, United Kingdom, Whole-Body Irradiation, Journal Article, Research Support, Non-U.S. Gov't
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 411603
URI: http://eprints.soton.ac.uk/id/eprint/411603
ISSN: 1083-8791
PURE UUID: 7a5ddac2-3461-41f5-9f70-5f97471ea8d9
ORCID for Kim Orchard: ORCID iD orcid.org/0000-0003-2276-3925

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Date deposited: 21 Jun 2017 16:31
Last modified: 17 Dec 2019 01:50

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Contributors

Author: Andrew D Chantry
Author: John A Snowden
Author: Charles Craddock
Author: Karl Peggs
Author: Claire Roddie
Author: Jenny I O Craig
Author: Kim Orchard ORCID iD
Author: Keiren E Towlson
Author: Rachel M Pearce
Author: David I Marks

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