Pocket Oncology (Pocket Notebook Series), 1st Ed.

ALLOGENEIC TRANSPLANTATION

Anita Kumar and Miguel-Angel Perales

Description

• Goal of Rx: Disease eradication via graft-vs.-tumor effect → therapeutic immune rxn of the grafted donor T lymphocytes against the recipient’s malignancy → offers a chance for cure or long-term remission (NEJM 1957;157(11):491)

• Tx w/chemotherapy and/or RT (conditioning) → followed by infusion of donor HSCs (Stem Cells 2001:9;108)

• In general, indicated for diseases that would not benefit from additional standard tx w/or are resistant to chemotherapy, includes malignant & non-malignant conditions (JAMA 2010;303:1617)

Conditioning Regimens

Chemotherapy and/or radiation prior to transplant to eradicate recipient’s disease & achieve immunosuppression (reducing the risk of graft rejection) prior to transplant

• Myeloablative regimens: Expected to destroy hematopoietic cells in the BM → result in pancytopenia that is long-lasting, usu irreversible, & in most instances fatal unless hematopoiesis is restored by infusion of HSCs

• Egs: TBI ≥5 Gy in a single dose or busulfan >8 mg/kg orally

• Nonmyeloablative regimens: Cause min. cytopenia but significant lymphopenia; following administration of allogeneic HSCs → engrafting donor T-cells will eventually eliminate host hematopoietic cells allowing establishment of donor hematopoiesis (JCO 2005;23:1993)

• Egs: Fludarabine plus cyclophosphamide w/or w/o antithymocyte globulin or TBI ≤2 Gy w/or w/o a purine analog

• Reduced-intensity regimens: Intermediate in intensity, result in cytopenias w/c may be prolonged & result in significant morbidity & mortality

• Egs: ≤9 mg/kg of oral busulfan or ≤140 mg/m2 of melphalan

Engraftment

• Expansion of HSC in recipient BM results in (1) normalization of blood counts, (2) recovery of the immune system that is donor-derived

• Time to engraftment depends on conditioning regimen: Ablative vs. nonablative, HSC graft source & characteristics (longer time to engraftment w/cord blood grafts)

Complications and Outcomes of Allogeneic Transplantation*

*Blood 2009;113:3604

Prognosis

• Relapse: In addition to frequent clinical/lab follow-up BM aspiration/bx is done at 1, 3, 6, 12, & 18 mos post-transplant to determine chimerism & r/o relapsed disease

• DLI may be administered for mixed chimerism or relapse

• Prognosis varies dependent upon disease type, stage, stem cell source, HLA-matched status, & conditioning regimens

• Mortality for allogeneic SCT can be estimated using the HCT-CI (Blood 2005;106:2912).