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

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 ph

Chapter 104 Acute and Chronic

Myeloid Leukemia

(Part 14)

The Patient

Patients should have acceptable end-organ function, be <70 years, and have

a healthy, histocompatible donor Furthermore, survival after SCT in the accelerated and blastic phases of the disease is significantly diminished and is associated with high rates of relapse Bone marrow transplantation (BMT) early in the chronic phase (1–2 years from diagnosis) is superior to later BMT In the imatinib era, allogeneic transplantation should be used when possible for patients with accelerated/blastic phases of the disease or those whose disease fails to respond or progresses on imatinib

The Donor

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 <1 year from diagnosis and

<30 years of age results in 5-year disease-free survival similar to matched-sibling donor transplantation

For all other groups, patients receiving BMT from unrelated donors have higher rates of graft failure and acute and chronic GVHD and prolonged convalescence after treatment, compared to those who receive allogeneic transplants from related donors

Sex mismatch has an adverse effect on transplantation, with worse outcome associated with a female donor and male recipient This has been attributed to GVHD against the male histocompatibility Y antigen

Peripheral blood is now being studied as a source of hematopoietic progenitor cells; it may offer rapid engraftment and less risk for the donor With unrelated donors, some studies demonstrated no difference in GVHD and

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