Impact of T Cell Chimerism on Clinical Outcome in 117 Patients Who Underwent Allogeneic Stem Cell Transplantation with a Busulfan-Containing Reduced-Intensity Conditioning Regimen

Bungo Saito, Takahiro Fukuda, Hiroki Yokoyama, Saiko Kurosawa, Toshihiro Takahashi, Shigeo Fuji, Noriko Takahashi, Kinuko Tajima, Sung Won Kim, Shin ichiro Mori, Ryuji Tanosaki, Yoichi Takaue, Yuji Heike

Research output: Contribution to journalArticle

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Abstract

Within the concept of reduced-intensity stem cell transplantation (RIST) there is a wide range of different regimens used, and little information is available on the clinical impact of chimerism status in patients conditioned with a busulfan-containing regimen. Therefore, we retrospectively reviewed lineage-specific chimerism and the subsequent clinical outcome in 117 patients (median age, 55 years; range: 29-68) who underwent busulfan-containing RIST. The conditioning regimen consisted of busulfan (oral 8 mg/kg or i.v. 6.4 mg/kg) and fludarabine (180 mg/m 2, n = 64) or cladribine (0.66 mg/kg, n = 53), with or without 2-4 Gy total-body irridiation (TBI) (n = 26) or antihuman T-lymphocyte immunoglobulin (ATG; 5-10 mg/kg; n = 31). Chimerism was evaluated with peripheral blood samples taken on days 30, 60, and 90 after transplantation by polymerase chain reaction (PCR)-based amplification of polymorphic short tandem repeat regions. The median follow-up of surviving patients was 1039 days (153-2535). The percent donor-chimerism was significantly higher in granulocyte than T cell fraction throughout the entire course, and the median (mean) values were, respectively, 100% (96%) versus 95% (83%), 100% (98%) versus 100% (89%), and 100% (98%) versus 100% (91%) at days 30, 60, and 90 after RIST. In a multivariate analysis, having received <2 types of chemotherapy regimens before RIST was the only factor that was significantly associated with low donor T cell chimerism (<60%) at day 30 (hazard ratio [HR]: 6.1; 95% confidence interval [CI], 2.1-18.4; P < .01). The median percentage of donor T cell chimerism at day 30 was 9% (0%-63%) in 5 patients who experienced graft failure, which was significantly lower than that (97%; 15%-100%) in the rest of the patients (P < .01). No correlation was found between the kinetics of T cell chimerism and the occurrence of acute or chronic GVHD (aGVHD, cGVHD). The stem cell source and the addition of TBI or ATG were not associated with the degree of T cell chimerism, overall survival (OS) or event-free survival (EFS). In a Cox proportional hazard model, low donor T cell chimerism of <60% at day 30 was associated with both poor OS (HR: 2.2; 95% CI, 1.1-4.5; P = .02) and EFS (HR: 2.0; 95% CI, 1.1-3.8; P = .02). In conclusion, we found that 43% of the patients retained mixed donor T cell chimerism (<90% donor) at day 30, whereas 92% achieved complete chimerism in granulocyte fraction. Low donor T cell chimerism of <60% at day 30 may predict a poor outcome, and a prospective study to examine the value of early intervention based on chimerism data is warranted.

Original languageEnglish
Pages (from-to)1148-1155
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume14
Issue number10
DOIs
Publication statusPublished - 2008 Oct
Externally publishedYes

Fingerprint

Busulfan
Chimerism
Stem Cell Transplantation
T-Lymphocytes
Tissue Donors
Confidence Intervals
Granulocytes
Disease-Free Survival
Cladribine
Survival
Proportional Hazards Models
Microsatellite Repeats
Immunoglobulins

Keywords

  • Busulfan
  • Chimerism
  • Reduced-intensity stem cell transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Impact of T Cell Chimerism on Clinical Outcome in 117 Patients Who Underwent Allogeneic Stem Cell Transplantation with a Busulfan-Containing Reduced-Intensity Conditioning Regimen. / Saito, Bungo; Fukuda, Takahiro; Yokoyama, Hiroki; Kurosawa, Saiko; Takahashi, Toshihiro; Fuji, Shigeo; Takahashi, Noriko; Tajima, Kinuko; Kim, Sung Won; Mori, Shin ichiro; Tanosaki, Ryuji; Takaue, Yoichi; Heike, Yuji.

In: Biology of Blood and Marrow Transplantation, Vol. 14, No. 10, 10.2008, p. 1148-1155.

Research output: Contribution to journalArticle

Saito, Bungo ; Fukuda, Takahiro ; Yokoyama, Hiroki ; Kurosawa, Saiko ; Takahashi, Toshihiro ; Fuji, Shigeo ; Takahashi, Noriko ; Tajima, Kinuko ; Kim, Sung Won ; Mori, Shin ichiro ; Tanosaki, Ryuji ; Takaue, Yoichi ; Heike, Yuji. / Impact of T Cell Chimerism on Clinical Outcome in 117 Patients Who Underwent Allogeneic Stem Cell Transplantation with a Busulfan-Containing Reduced-Intensity Conditioning Regimen. In: Biology of Blood and Marrow Transplantation. 2008 ; Vol. 14, No. 10. pp. 1148-1155.
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abstract = "Within the concept of reduced-intensity stem cell transplantation (RIST) there is a wide range of different regimens used, and little information is available on the clinical impact of chimerism status in patients conditioned with a busulfan-containing regimen. Therefore, we retrospectively reviewed lineage-specific chimerism and the subsequent clinical outcome in 117 patients (median age, 55 years; range: 29-68) who underwent busulfan-containing RIST. The conditioning regimen consisted of busulfan (oral 8 mg/kg or i.v. 6.4 mg/kg) and fludarabine (180 mg/m 2, n = 64) or cladribine (0.66 mg/kg, n = 53), with or without 2-4 Gy total-body irridiation (TBI) (n = 26) or antihuman T-lymphocyte immunoglobulin (ATG; 5-10 mg/kg; n = 31). Chimerism was evaluated with peripheral blood samples taken on days 30, 60, and 90 after transplantation by polymerase chain reaction (PCR)-based amplification of polymorphic short tandem repeat regions. The median follow-up of surviving patients was 1039 days (153-2535). The percent donor-chimerism was significantly higher in granulocyte than T cell fraction throughout the entire course, and the median (mean) values were, respectively, 100{\%} (96{\%}) versus 95{\%} (83{\%}), 100{\%} (98{\%}) versus 100{\%} (89{\%}), and 100{\%} (98{\%}) versus 100{\%} (91{\%}) at days 30, 60, and 90 after RIST. In a multivariate analysis, having received <2 types of chemotherapy regimens before RIST was the only factor that was significantly associated with low donor T cell chimerism (<60{\%}) at day 30 (hazard ratio [HR]: 6.1; 95{\%} confidence interval [CI], 2.1-18.4; P < .01). The median percentage of donor T cell chimerism at day 30 was 9{\%} (0{\%}-63{\%}) in 5 patients who experienced graft failure, which was significantly lower than that (97{\%}; 15{\%}-100{\%}) in the rest of the patients (P < .01). No correlation was found between the kinetics of T cell chimerism and the occurrence of acute or chronic GVHD (aGVHD, cGVHD). The stem cell source and the addition of TBI or ATG were not associated with the degree of T cell chimerism, overall survival (OS) or event-free survival (EFS). In a Cox proportional hazard model, low donor T cell chimerism of <60{\%} at day 30 was associated with both poor OS (HR: 2.2; 95{\%} CI, 1.1-4.5; P = .02) and EFS (HR: 2.0; 95{\%} CI, 1.1-3.8; P = .02). In conclusion, we found that 43{\%} of the patients retained mixed donor T cell chimerism (<90{\%} donor) at day 30, whereas 92{\%} achieved complete chimerism in granulocyte fraction. Low donor T cell chimerism of <60{\%} at day 30 may predict a poor outcome, and a prospective study to examine the value of early intervention based on chimerism data is warranted.",
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T1 - Impact of T Cell Chimerism on Clinical Outcome in 117 Patients Who Underwent Allogeneic Stem Cell Transplantation with a Busulfan-Containing Reduced-Intensity Conditioning Regimen

AU - Saito, Bungo

AU - Fukuda, Takahiro

AU - Yokoyama, Hiroki

AU - Kurosawa, Saiko

AU - Takahashi, Toshihiro

AU - Fuji, Shigeo

AU - Takahashi, Noriko

AU - Tajima, Kinuko

AU - Kim, Sung Won

AU - Mori, Shin ichiro

AU - Tanosaki, Ryuji

AU - Takaue, Yoichi

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N2 - Within the concept of reduced-intensity stem cell transplantation (RIST) there is a wide range of different regimens used, and little information is available on the clinical impact of chimerism status in patients conditioned with a busulfan-containing regimen. Therefore, we retrospectively reviewed lineage-specific chimerism and the subsequent clinical outcome in 117 patients (median age, 55 years; range: 29-68) who underwent busulfan-containing RIST. The conditioning regimen consisted of busulfan (oral 8 mg/kg or i.v. 6.4 mg/kg) and fludarabine (180 mg/m 2, n = 64) or cladribine (0.66 mg/kg, n = 53), with or without 2-4 Gy total-body irridiation (TBI) (n = 26) or antihuman T-lymphocyte immunoglobulin (ATG; 5-10 mg/kg; n = 31). Chimerism was evaluated with peripheral blood samples taken on days 30, 60, and 90 after transplantation by polymerase chain reaction (PCR)-based amplification of polymorphic short tandem repeat regions. The median follow-up of surviving patients was 1039 days (153-2535). The percent donor-chimerism was significantly higher in granulocyte than T cell fraction throughout the entire course, and the median (mean) values were, respectively, 100% (96%) versus 95% (83%), 100% (98%) versus 100% (89%), and 100% (98%) versus 100% (91%) at days 30, 60, and 90 after RIST. In a multivariate analysis, having received <2 types of chemotherapy regimens before RIST was the only factor that was significantly associated with low donor T cell chimerism (<60%) at day 30 (hazard ratio [HR]: 6.1; 95% confidence interval [CI], 2.1-18.4; P < .01). The median percentage of donor T cell chimerism at day 30 was 9% (0%-63%) in 5 patients who experienced graft failure, which was significantly lower than that (97%; 15%-100%) in the rest of the patients (P < .01). No correlation was found between the kinetics of T cell chimerism and the occurrence of acute or chronic GVHD (aGVHD, cGVHD). The stem cell source and the addition of TBI or ATG were not associated with the degree of T cell chimerism, overall survival (OS) or event-free survival (EFS). In a Cox proportional hazard model, low donor T cell chimerism of <60% at day 30 was associated with both poor OS (HR: 2.2; 95% CI, 1.1-4.5; P = .02) and EFS (HR: 2.0; 95% CI, 1.1-3.8; P = .02). In conclusion, we found that 43% of the patients retained mixed donor T cell chimerism (<90% donor) at day 30, whereas 92% achieved complete chimerism in granulocyte fraction. Low donor T cell chimerism of <60% at day 30 may predict a poor outcome, and a prospective study to examine the value of early intervention based on chimerism data is warranted.

AB - Within the concept of reduced-intensity stem cell transplantation (RIST) there is a wide range of different regimens used, and little information is available on the clinical impact of chimerism status in patients conditioned with a busulfan-containing regimen. Therefore, we retrospectively reviewed lineage-specific chimerism and the subsequent clinical outcome in 117 patients (median age, 55 years; range: 29-68) who underwent busulfan-containing RIST. The conditioning regimen consisted of busulfan (oral 8 mg/kg or i.v. 6.4 mg/kg) and fludarabine (180 mg/m 2, n = 64) or cladribine (0.66 mg/kg, n = 53), with or without 2-4 Gy total-body irridiation (TBI) (n = 26) or antihuman T-lymphocyte immunoglobulin (ATG; 5-10 mg/kg; n = 31). Chimerism was evaluated with peripheral blood samples taken on days 30, 60, and 90 after transplantation by polymerase chain reaction (PCR)-based amplification of polymorphic short tandem repeat regions. The median follow-up of surviving patients was 1039 days (153-2535). The percent donor-chimerism was significantly higher in granulocyte than T cell fraction throughout the entire course, and the median (mean) values were, respectively, 100% (96%) versus 95% (83%), 100% (98%) versus 100% (89%), and 100% (98%) versus 100% (91%) at days 30, 60, and 90 after RIST. In a multivariate analysis, having received <2 types of chemotherapy regimens before RIST was the only factor that was significantly associated with low donor T cell chimerism (<60%) at day 30 (hazard ratio [HR]: 6.1; 95% confidence interval [CI], 2.1-18.4; P < .01). The median percentage of donor T cell chimerism at day 30 was 9% (0%-63%) in 5 patients who experienced graft failure, which was significantly lower than that (97%; 15%-100%) in the rest of the patients (P < .01). No correlation was found between the kinetics of T cell chimerism and the occurrence of acute or chronic GVHD (aGVHD, cGVHD). The stem cell source and the addition of TBI or ATG were not associated with the degree of T cell chimerism, overall survival (OS) or event-free survival (EFS). In a Cox proportional hazard model, low donor T cell chimerism of <60% at day 30 was associated with both poor OS (HR: 2.2; 95% CI, 1.1-4.5; P = .02) and EFS (HR: 2.0; 95% CI, 1.1-3.8; P = .02). In conclusion, we found that 43% of the patients retained mixed donor T cell chimerism (<90% donor) at day 30, whereas 92% achieved complete chimerism in granulocyte fraction. Low donor T cell chimerism of <60% at day 30 may predict a poor outcome, and a prospective study to examine the value of early intervention based on chimerism data is warranted.

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