Fetomaternal and maternofetal cell transfer have been described. Their clinical relevance is unknown. We hypothesized that firstborn siblings could tolerize their siblings born thereafter through sequential fetomaternal-maternofetal cell transfer. Hence, stem cell transplants within a family from a firstborn sibling (group A) should result more graft-versus-host disease (GvHD) and worse overall survival than transplants to a firstborn donor (group B). Results of a retrospective single center cohort analysis of 321 HLA-identical sibling donor hemopoietic stem cell transplants showed a survival of 48.3% (+/−10.9%) at 10 years in the group with firstborn donors (group A, 110 patients) as compared to 63.2 (+/−10.6%) in the group with firstborn recipients (group B, 105 patients; p<0.02) and a RR of death after adjustment for other risk factors of 2.6 (CI 1.45–4.66; p<0.001) for the group with firstborn donors. These results support the concept of a clinically relevant tolerizing effect of birth order, possibly mediated by fetomaternal cell transfer in man.

Patients characteristics and outcomes

Birth OrderDonor First SiblingRecipient First Sibling
 n 110 105  
Donor Age median (range) 30.1 (4.9–68) 25.4 (0.4–59.1) p=0.005 
Recipient Age median (range) 25.4(3.2–62.1) 30.8 (2.2–63.0)  
Number of Siblings 2 67 69 n.s. 
 3 26 22  
 >3 17 14  
Diagnosis    n.s. 
Acute myeloid leukemia n 33 26  
Acute lymphoblastic leukemia n 24 24  
Chronic myeloid leukemia n 23 23  
Lymphoproliferative disorders n 14 13  
Severe aplastic anemia n 11 12  
Myelodysplastic syndromes n 5 7  
Stem Cell Source    n.s. 
Bone Marrow n 71 73  
PBSCT n 39 32  
Conditioning    n.s. 
With totoal body irradiation n 18 22  
Without total body irradiation n 92 83  
Outcomes     
Survival at 10 yrs % 48.3 63.2 p<0.02 
Relapse at 3 yrs. % 26 20 n.s. 
Acute GvHD    p=0.017 
< Grade II n 46 61  
>= Grade II n 64 44  
Chronic GvHD    n.s. 
none n 28 30  
n.a. n 29 17  
Limited n 32 30  
Extensive n 21 23  
Birth OrderDonor First SiblingRecipient First Sibling
 n 110 105  
Donor Age median (range) 30.1 (4.9–68) 25.4 (0.4–59.1) p=0.005 
Recipient Age median (range) 25.4(3.2–62.1) 30.8 (2.2–63.0)  
Number of Siblings 2 67 69 n.s. 
 3 26 22  
 >3 17 14  
Diagnosis    n.s. 
Acute myeloid leukemia n 33 26  
Acute lymphoblastic leukemia n 24 24  
Chronic myeloid leukemia n 23 23  
Lymphoproliferative disorders n 14 13  
Severe aplastic anemia n 11 12  
Myelodysplastic syndromes n 5 7  
Stem Cell Source    n.s. 
Bone Marrow n 71 73  
PBSCT n 39 32  
Conditioning    n.s. 
With totoal body irradiation n 18 22  
Without total body irradiation n 92 83  
Outcomes     
Survival at 10 yrs % 48.3 63.2 p<0.02 
Relapse at 3 yrs. % 26 20 n.s. 
Acute GvHD    p=0.017 
< Grade II n 46 61  
>= Grade II n 64 44  
Chronic GvHD    n.s. 
none n 28 30  
n.a. n 29 17  
Limited n 32 30  
Extensive n 21 23  
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Figure 1:
Figure 1:. Kaplan Meyer estimate of cumulative survival of groups A(firstborn donor: gray line) and B (firstborn recipient: black line). + indicates censored patient.
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Kaplan Meyer estimate of cumulative survival of groups A(firstborn donor: gray line) and B (firstborn recipient: black line). + indicates censored patient.

Figure 1:
Figure 1:. Kaplan Meyer estimate of cumulative survival of groups A(firstborn donor: gray line) and B (firstborn recipient: black line). + indicates censored patient.
View largeDownload slide

Kaplan Meyer estimate of cumulative survival of groups A(firstborn donor: gray line) and B (firstborn recipient: black line). + indicates censored patient.

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Topics:
birth order, donors, hematopoietic stem cells, human leukocyte antigens, relationship - sibling, transfer technique, graft-versus-host disease, acute lymphocytic leukemia, aplastic anemia, graft-versus-host disease, acute

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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