The impact of acute and chronic graft-versus-host disease on normal and malignant B-lymphoid precursors after allogeneic stem cell transplantation for B-lineage acute lymphoblastic leukemia.
OBJECTIVE
The development of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT) for B-lineage acute lymphoblastic leukemia (B-ALL) is associated with a lower probability of leukemia relapse. However, mechanisms by which this GVHD-associated graft-versus-leukemia effect is exerted are poorly understood. In this study, we simultaneously traced the kinetics of normal donor-derived and leukemic recipient-derived B-lymphopoiesis comparing patients with or without GVHD.


METHODS
We used multiparameter flow-cytometry to quantify pro-B (CD19+CD10+CD34+), pre-B (CD19+CD10+CD34-) precursors and malignant lymphoblasts identified by leukemia-associated markers in 161 prospective marrow samples from 39 consecutive B-ALL patients after allogeneic SCT. Chimerism analysis was performed by quantitative real-time polymerase chain reaction of null alleles and insertion/deletion (indel) polymorphisms.


RESULTS
Acute GVHD of grades II-IV is associated with a strong inhibition of normal donor-derived pro-B and pre-B precursors at days +30 and +60 post-SCT. Patients who develop chronic GVHD have lower percentages of marrow B-cell precursors during the first year after SCT. Likewise, recipient-derived leukemia B cells were absent at days +30 and +60 in patients with acute GVHD grades II-IV and were less likely to be detected in patients with chronic GVHD. Induction of GVHD as treatment of increasing amounts of leukemia cells causes inhibition of both normal and malignant B compartments even in the absence of steroid therapy.


CONCLUSIONS
We conclude that the development of GVHD after allogeneic SCT is associated with a non-specific inhibition of B-lymphopoiesis.
Hematology and Bone Marrow transplantation Department, University Hospital Reina Sofía, Avda. Menendez Pidal s/n, 14004 Córdoba, Spain. joaquin.sanchez@cheerful.com
Joaquín
J
Sánchez-García
Josefina
J
Serrano
Pedro
P
Gómez
Francisco
F
Martínez
Carmen
C
Martín
José
J
Román-Gómez
Antonia
A
Rodríguez
Concepción
C
Herrera
José M
JM
García
Miguel A
MA
Alvarez
Antonio
A
Torres
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002051:Burkitt Lymphoma / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000276:immunology / Q000601:surgery; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous