Chapter 108. Hematopoietic Cell Transplantation (Part 9)

Chronic Leukemia Allogeneic hematopoietic cell transplantation is the only therapy shown to cure a substantial portion of patients with chronic myeloid leukemia (CML). Fiveyear disease-free survival rates are 15–20% for patients transplanted for blast crisis, 25–50% for accelerated-phase patients, and 60–70% for chronic phase patients, with cure rates as high as 80% at selected centers. Use of unrelated donors results in more GVHD and slightly worse survival than seen with matched siblings, although 3-year disease-free survival rates of 70% have been reported at some large centers. The timing of transplantation in CML has become more complicated with the introduction...
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Chapter 108. Hematopoietic Cell Transplantation (Part 9) Chapter 108. Hematopoietic Cell Transplantation (Part 9) Chronic Leukemia Allogeneic hematopoietic cell transplantation is the only therapy shown tocure a substantial portion of patients with chronic myeloid leukemia (CML). Five-year disease-free survival rates are 15–20% for patients transplanted for blastcrisis, 25–50% for accelerated-phase patients, and 60–70% for chronic phasepatients, with cure rates as high as 80% at selected centers. Use of unrelateddonors results in more GVHD and slightly worse survival than seen with matchedsiblings, although 3-year disease-free survival rates of 70% have been reported atsome large centers. The timing of transplantation in CML has become morecomplicated with the introduction of imatinib mesylate, a remarkably effective,relatively nontoxic oral agent. Even though imatinib is not generally regarded ascurative, given its favorable toxicity profile, most physicians favor its use as initialtherapy for CML, with transplantation being reserved for those who fail to achievea complete cytogenetic response with imatinib, relapse after an initial response, orare intolerant of the drug (Chap. 104). Allogeneic transplantation has been used to only a limited extent forchronic lymphocytic leukemia, in large part because of the chronic nature of thedisease and because of the age profile of patients. With allogeneic transplantation,complete remissions have been achieved in the majority of patients so far reported,with disease-free survival rates of ~50% at 3 years. However, treatment-relatedmortality has been substantial, and further follow-up is needed. Encouragingresults have been seen using reduced intensity preparative regimens beforeallogeneic transplantation. Myelodysplasia Between 40 and 50% of patients with myelodysplasia appear to be curedwith allogeneic transplantation. Results are better among younger patients andthose with less-advanced disease. However, some patients with myelodysplasiacan live for extended periods without intervention, and so transplantation isgenerally recommended only for patients with disease categorized as intermediaterisk I or greater according to the International Prognostic Scoring System (Chap.102). Lymphoma Patients with disseminated intermediate- or high-grade non-Hodgkinslymphoma who have not been cured by first-line chemotherapy and aretransplanted in first relapse or second remission can still be cured in 40–50% ofcases. This represents a clear advantage over results obtained with conventional-dose salvage chemotherapy. It is unsettled whether patients with high-risk diseasebenefit from transplantation in first remission. Most experts favor the use ofautologous rather than allogeneic transplantation for patients with intermediate orhigh grade non-Hodgkins lymphoma, because fewer complications occur with thisapproach and survival appears equivalent. For patients with recurrent disseminatedindolent non-Hodgkins lymphoma, autologous transplantation results in highresponse rates and improved progression-free survival compared to salvagechemotherapy. However, late relapses are seen after transplantation. The role ofautologous transplantation in the initial treatment of patients is under study.Nonmyeloablative preparative regimens followed by allogeneic transplantationresult in high response rates in patients with indolent lymphomas, but the exactrole of this approach remains to be defined. The role of transplantation in Hodgkins disease is similar to that inintermediate- and high-grade non-Hodgkins lymphoma. With transplantation, 5-year disease-free survival is 20–30% in patients who never achieve a firstremission with standard chemotherapy and up to 70% for those transplanted insecond remission. Transplantation has no defined role in first remission inHodgkins disease. Myeloma Patients with myeloma who have progressed on first-line therapy cansometimes benefit from allogeneic or autologous transplantation. Autologoustransplantation has been studied as part of the initial therapy of patients, and bothdisease-free survival as well as overall survival were improved with this approachin randomized trials. The use of autologous transplantation followed bynonmyeloablative allogeneic transplantation has shown encouraging results. Solid Tumors Among women with metastatic breast cancer, 15–20% disease-free survivalrates at 3 years have been reported, with better results seen in younger patientswho have responded completely to standard-dose therapy before undergoingtransplantation. Randomized trials have not shown superior survival for patientstreated for metastatic disease wit ...