Stem cell transplantation for chronic myeloid leukaemia: the role of infused marrow cell dose.
BACKGROUND
Allogeneic stem cell transplantation is a potentially curative option for patients with CML. The optimal donor is an HLA-identical sibling but transplants using unrelated volunteers can also be successful. The factors influencing survival after allogeneic SCT for CML are reasonably well defined. Recently however, the Seattle group have emphasised the influence of a high marrow cell dose on outcome following volunteer unrelated donor SCT for high risk acute leukaemia.


METHODS
We have sought to define factors impacting on transplant related mortality (TRM) in a population of CML patients after allografting with matched sibling or alternative stem cell donors at a single centre over a 20-year period, with emphasis on infused marrow cell dose. Factors entered into a multivariate analysis were: recipient age, recipient CMV serostatus, disease phase, donor sex, cell dose and frequency of CTLP reactivity.


RESULTS
In multivariate analysis four factors had an adverse effect on TRM when using a VUD: low marrow cell dose (<3.65 x 10(8) TNC/kg, relative risk 2.05, CI 1.08-3.90, P = 0.029), late disease phase (relative risk 1.68, CI 1.03-2.74, P = 0.038), patient CMV seropositivity (relative risk 1.98, CI 1.25-3.13, P = 0.004) and high frequency of CTLP (relative risk 1.93, CI 1.18-3.13, P = 0.008). For HLA-identical sibling donor transplants the only factor that adversely impacted on TRM was late disease phase (P = 0.0004 in univariate analysis).


CONCLUSIONS
High infused cell dose is a new modifiable factor associated with reduced TRM following allogeneic SCT using an unrelated donor for the treatment of CML. The data support the recommendation that bone marrow harvest teams should aim to collect the highest possible number of nucleated cells for recipients of unrelated donor transplants.
Pocock
C
C
Department of Haematology, Hammersmith Hospital, Imperial College School of Medicine, London, UK.
Szydlo
R
R
Davis
J
J
de La Fuente
J
J
Craddock
C
C
Cwynarski
K
K
Olavarria
E
E
Rezvani
K
K
Kanfer
E
E
Apperley
J
J
Goldman
J
J
D000328:Adult; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods* / Q000401:mortality; D002452:Cell Count; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy*; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome