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

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Nội dung Text: 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 or mismatched at only one HLA locus, should be considered for any patient with CML who is a candidate for an HLA-related sibling transplant. Syngeneic BMT in patients with chronic-phase CML results in 7-year disease-free survival in 55% of patients, with a 30% relapse rate. BMT with an HLA-identical sibling in the chronic phase achieves 5-year disease-free survival in 40–70% of patients, with a 25% relapse rate. BMT from an HLA-matched unrelated donor in chronic phase
improved disease-free survival when comparing peripheral blood to bone marrow stem cells. Using matched sibling donors in chronic-phase CML, marrow stem cells led to a higher cumulative incidence of relapse at 3 years, while peripheral blood stem cell recipients had a higher cumulative incidence of chronic GVHD. At the current time, some centers collect bone marrow and some peripheral blood from sibling 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 obtaining a 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 plus cyclophosphamide in the 3-year probabilities of survival, relapse, event-free survival, speed of engraftment, and incidence of venoocclusive disease of the liver. Significantly more patients in the total-body irradiation arm experienced major elevations of creatinine, acute GVHD, longer periods of fever, positive blood cultures, hospital admissions, and longer inpatient hospital stays. However, increased chronic GVHD, obstructive bronchiolitis, and alopecia were noted with
busulphan. Measurement of busulphan levels revealed no significant association between busulphan levels and regimen-related toxicity, but low levels were associated with an increased risk of relapse. Intravenous busulphan allows better control of serum levels. Reduced-intensity transplants in which the preparative regimen is aimed at eliminating host lymphocytes rather than bone marrow have been reported by numerous groups. No randomized trials comparing the two approaches have been published. Retrospective comparisons reveal that reduced-intensity conditioning regimens produce equivalent or acceptable results (in toxicity as well as outcome). Reduced toxicity with preserved antitumor efficacy is the goal, and therefore reduced-intensity transplantation is our recommendation. Development and Type of GVHD Development of grade I GVHD (Chap. 108) decreases the risk of relapse compared to no GVHD. An even lower relapse rate was observed in patients with grade II GVHD but was accompanied by a substantially higher transplant-related mortality rate. The decreased relapse rate may be caused by a GVL effect. Depletion of T lymphocytes from donor marrow can prevent GVHD but results in an increased risk of relapse, which exceeds the relapse rate after syngeneic SCT. Thus, T lymphocytes from the donor marrow mediate a significant antileukemic or
GVL effect, and even syngeneic marrow may exhibit limited GVL activity in CML.