Table 1.

Microsatellite analysis of colon mucosa













Laser-microdissected crypts
Tetranucleotides
HCT/chemo and patient ID
Age, y/sex
Disease
History of chemo*
Preparative regimen/last chemo
Reason for colon biopsy
D of sampling
Pathology of biopsy
Clinical GI-GvHD stage at sampling
Overall max GvHD§
Whole colon section
THO-1
SEE33
D14S120
Mononucleotides
Allo               
   C1   61/F   AML   Yes   FBM   Diar   18   N   0   0   S   S   S   S   S  
   C2   52/M   AML   Yes   BuCy   Diar   20   I°   I°   I°   S   S   MSI   S   S  
   C3#  53/M   CML   No   BuCy   Diar   30   I°   I°   I°   S   MSI   NE   S   S  
   C4   19/M   ALL   Yes   TBI/VC   Diar   42   I°   II°   III°   S   MSI   MSI   S   S  
   C5   68/M   AML   No   FBM   Diar   46   III°   III°   III°   S   S   MSI   S   S  
   C6   59/M   MM   Yes   2Gy/F   Diar   46   III°   III°   III°   NE   S   MSI   S   S  
   C7   65/M   AML   Yes   FBM   Diar   49   II°   II°   III°   S   S   S   S   S  
   C8   45/F   ALL   Yes   BuCy   Diar   57   III°   III°   IV°   S   MSI   MSI   S   S  
   C9   29/M   CML   Yes   BuCy   Diar   61   II°   II°   IV°   MSI   NE   MSI   S   S  
   C10   61/F   AML   Yes   FBM   Diar   92   I°   I°   III°   MSI   MSI   NE   NE   S  
   C11   20/M   ALL   Yes   TBI/VC   Diar   148   N   0   Ext   S   NE   S   S   S  
   C12   52/M   CML   No   FBM   Diar   175   I°   I°   I°   MSI   S   MSI   NE   S  
   C13   45/M   AML   Yes   BuCy   Diar   182   II°   II°   Ext   S   MSI   MSI   S   S  
   C14   36/M   NHL   Yes   BuCy   FU   277   N   0   0   MSI   MSI   S   MSI   S  
   C15   49/F   CML   No   FBM   Diar   543   I°   I°   Ext   S   MSI   MSI   NE   S  
   C16   45/F   MDS   No   BuCy   Diar   1089   Col   0   Ext   S   S   S   S   S  
Chemo               
   C17   52/F   EsCa   Yes   Vino   Diar   7   N   NA   NA   S   S   S   NE   S  
   C18   20/F   HD   No   HD15   Diar   10   Col   NA   NA   S   NE   S   NE   S  
   C19   72/F   NHL   Yes   Chlor   FU   240   N   NA   NA   S   S   S   S   S  
   C20   66/F   Col Ca   No   5-FU   FU   1805   N   NA   NA   NE   S   S   S   S  
None               
   C21   65/F   HepC   NA   NA   TuScr   NA   N   NA   NA   S   S   S   S   S  
   C22   73/M   Healthy   NA   NA   TuScr   NA   N   NA   NA   S   S   S   S   S  
   C23   48/M   Healthy   NA   NA   TuScr   NA   N   NA   NA   S   S   S   S   S  
   C24   69/F   Divert   NA   NA   TuScr   NA   N   NA   NA   S   S   S   S   S  
   C25   39/F   Col irr   NA   NA   A pain   NA   N   NA   NA   S   S   S   S   S  
   C26   57/F   Divert   NA   NA   A pain   NA   N   NA   NA   S   S   S   S   S  
   C27   83/F   BrCa   No   NA   Bleed   NA   N   NA   NA   S   S   S   NE   S  
   C3#
 
53/M
 
CML
 
No
 
NA
 
A pain
 
NA
 
N
 
NA
 
NA
 
S
 
S
 
NE
 
S
 
S
 












Laser-microdissected crypts
Tetranucleotides
HCT/chemo and patient ID
Age, y/sex
Disease
History of chemo*
Preparative regimen/last chemo
Reason for colon biopsy
D of sampling
Pathology of biopsy
Clinical GI-GvHD stage at sampling
Overall max GvHD§
Whole colon section
THO-1
SEE33
D14S120
Mononucleotides
Allo               
   C1   61/F   AML   Yes   FBM   Diar   18   N   0   0   S   S   S   S   S  
   C2   52/M   AML   Yes   BuCy   Diar   20   I°   I°   I°   S   S   MSI   S   S  
   C3#  53/M   CML   No   BuCy   Diar   30   I°   I°   I°   S   MSI   NE   S   S  
   C4   19/M   ALL   Yes   TBI/VC   Diar   42   I°   II°   III°   S   MSI   MSI   S   S  
   C5   68/M   AML   No   FBM   Diar   46   III°   III°   III°   S   S   MSI   S   S  
   C6   59/M   MM   Yes   2Gy/F   Diar   46   III°   III°   III°   NE   S   MSI   S   S  
   C7   65/M   AML   Yes   FBM   Diar   49   II°   II°   III°   S   S   S   S   S  
   C8   45/F   ALL   Yes   BuCy   Diar   57   III°   III°   IV°   S   MSI   MSI   S   S  
   C9   29/M   CML   Yes   BuCy   Diar   61   II°   II°   IV°   MSI   NE   MSI   S   S  
   C10   61/F   AML   Yes   FBM   Diar   92   I°   I°   III°   MSI   MSI   NE   NE   S  
   C11   20/M   ALL   Yes   TBI/VC   Diar   148   N   0   Ext   S   NE   S   S   S  
   C12   52/M   CML   No   FBM   Diar   175   I°   I°   I°   MSI   S   MSI   NE   S  
   C13   45/M   AML   Yes   BuCy   Diar   182   II°   II°   Ext   S   MSI   MSI   S   S  
   C14   36/M   NHL   Yes   BuCy   FU   277   N   0   0   MSI   MSI   S   MSI   S  
   C15   49/F   CML   No   FBM   Diar   543   I°   I°   Ext   S   MSI   MSI   NE   S  
   C16   45/F   MDS   No   BuCy   Diar   1089   Col   0   Ext   S   S   S   S   S  
Chemo               
   C17   52/F   EsCa   Yes   Vino   Diar   7   N   NA   NA   S   S   S   NE   S  
   C18   20/F   HD   No   HD15   Diar   10   Col   NA   NA   S   NE   S   NE   S  
   C19   72/F   NHL   Yes   Chlor   FU   240   N   NA   NA   S   S   S   S   S  
   C20   66/F   Col Ca   No   5-FU   FU   1805   N   NA   NA   NE   S   S   S   S  
None               
   C21   65/F   HepC   NA   NA   TuScr   NA   N   NA   NA   S   S   S   S   S  
   C22   73/M   Healthy   NA   NA   TuScr   NA   N   NA   NA   S   S   S   S   S  
   C23   48/M   Healthy   NA   NA   TuScr   NA   N   NA   NA   S   S   S   S   S  
   C24   69/F   Divert   NA   NA   TuScr   NA   N   NA   NA   S   S   S   S   S  
   C25   39/F   Col irr   NA   NA   A pain   NA   N   NA   NA   S   S   S   S   S  
   C26   57/F   Divert   NA   NA   A pain   NA   N   NA   NA   S   S   S   S   S  
   C27   83/F   BrCa   No   NA   Bleed   NA   N   NA   NA   S   S   S   NE   S  
   C3#
 
53/M
 
CML
 
No
 
NA
 
A pain
 
NA
 
N
 
NA
 
NA
 
S
 
S
 
NE
 
S
 
S
 

At the time of colon sampling all patients revealed complete donor chimerism in blood (blood chimerism analysis in patients C1 and C2 was done at day 30).

Chemo indicates chemotherapy; HCT, hematopoietic cell transplantation; GI, gastrointestinal; GvHD, graft-versus-host disease; AML, acute myeloid leukemia; Allo, allogeneic HCT; FBM, fludarabine, carmustine, melphalan (reduced intensity conditioning); Diar, diarrhea; S, stable microsatellites; BuCy, busulphan, cyclophosphamide; MSI, microsatellite instability; CML, chronic myeloid leukemia; NE, not evaluable; ALL, acute lymphatic leukemia; TBI/VC, total body irradiation (12 Gy), etoposide phosphate, cyclophosphamide; MM, multiple myeloma; 2Gy/F: low total body irradiation (2 Gy), fludarabine (reduced intensity conditioning); NHL, non-Hodgkin lymphoma; FU, follow-up; MDS, myelodysplastic syndrome; Col, colon; EsCa, esophagus cancer; Vino, vinorelbine; NA, not applicable; HD, Hodgkin disease; HD15, procarbazine, cyclophosphamide, etoposide phosphate, vincristine, bleomycin; Chlor, chlorambucil; Ca, cancer; 5-FU, 5-fluoruracil; HepC, hepatitis C; TuScr, tumor screening; Div, diverticulosis; irr, irritable; A pain, abdominal pain; BrCa, breast cancer.

*

History of multiple (≥ 3) myelosuppressive chemotherapies before HCT

Day after HCT or last chemotherapy

N indicates normal; Col, infectious colitis; I to IV, pathologic grading of GvHD

§

Occurrence of graft-versus-host disease (GvHD) any time after HCT, maximal grade; 0 indicates no GvHD; I-IV, grade acute GvHD; Ext, extensive chronic GvHD

Microsatellite PCR using as template DNA extracted from the whole colon section. In these cases, MSI denotes MSI in at least one marker and S no MSI in all markers

ZP3, BAT26, SRY

#

A gastric biopsy obtained from patient C3 before transplantation showed no MSI. This patient developed squamous cancer of his tongue 3.5 years after allogeneic HCT (see Table 3)

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