Chapter 104. Acute and Chronic Myeloid Leukemia (Part 14)

Tham khảo tài liệu chapter 104. acute and chronic myeloid leukemia (part 14), y tế - sức khoẻ, y học thường thức phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 14) Chapter 104. Acute and Chronic Myeloid Leukemia (Part 14) The Patient Patients should have acceptable end-organ function, be Transplantation from a family donor, who is either fully matched ormismatched at only one HLA locus, should be considered for any patient withCML who is a candidate for an HLA-related sibling transplant. Syngeneic BMT inpatients with chronic-phase CML results in 7-year disease-free survival in 55% ofpatients, with a 30% relapse rate. BMT with an HLA-identical sibling in the chronic phase achieves 5-yeardisease-free survival in 40–70% of patients, with a 25% relapse rate. BMT froman HLA-matched unrelated donor in chronic phase improved disease-free survival when comparing peripheral blood to bone marrowstem cells. Using matched sibling donors in chronic-phase CML, marrow stem cellsled to a higher cumulative incidence of relapse at 3 years, while peripheral bloodstem cell recipients had a higher cumulative incidence of chronic GVHD. At thecurrent time, some centers collect bone marrow and some peripheral blood fromsibling donors for newly diagnosed chronic-phase CML patients. Patients with more advanced stages are offered peripheral blood SCT.Umbilical-cord blood may permit mismatched SCT with notably less GVHD;GVL effects do not appear to be impaired. A problem with cord blood is obtaininga sufficient number of progenitor cells to reconstitute hematopoiesis in an adult. Preparative Regimens Myeloablative regimens have been studied by several groups.Cyclophosphamide plus total-body irradiation is comparable to busulphan pluscyclophosphamide in the 3-year probabilities of survival, relapse, event-freesurvival, speed of engraftment, and incidence of venoocclusive disease of theliver. Significantly more patients in the total-body irradiation arm experiencedmajor elevations of creatinine, acute GVHD, longer periods of fever, positiveblood cultures, hospital admissions, and longer inpatient hospital stays. However,increased chronic GVHD, obstructive bronchiolitis, and alopecia were noted withbusulphan. Measurement of busulphan levels revealed no significant associationbetween busulphan levels and regimen-related toxicity, but low levels wereassociated with an increased risk of relapse. Intravenous busulphan allows bettercontrol of serum levels. Reduced-intensity transplants in which the preparative regimen is aimed ateliminating host lymphocytes rather than bone marrow have been reported bynumerous groups. No randomized trials comparing the two approaches have beenpublished. Retrospective comparisons reveal that reduced-intensity conditioningregimens produce equivalent or acceptable results (in toxicity as well as outcome).Reduced toxicity with preserved antitumor efficacy is the goal, and thereforereduced-intensity transplantation is our recommendation. Development and Type of GVHD Development of grade I GVHD (Chap. 108) decreases the risk of relapsecompared to no GVHD. An even lower relapse rate was observed in patients withgrade II GVHD but was accompanied by a substantially higher transplant-relatedmortality rate. The decreased relapse rate may be caused by a GVL effect.Depletion of T lymphocytes from donor marrow can prevent GVHD but results inan increased risk of relapse, which exceeds the relapse rate after syngeneic SCT.Thus, T lymphocytes from the donor marrow mediate a significant antileukemic orGVL effect, and even syngeneic marrow may exhibit limited GVL activity inCML.