Chapter 108. Hematopoietic Cell Transplantation (Part 9)

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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) Chronic Leukemia Allogeneic hematopoietic cell transplantation is the only therapy shown to cure a substantial portion of patients with chronic myeloid leukemia (CML). Five- year 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 of imatinib mesylate, a remarkably effective,
relatively nontoxic oral agent. Even though imatinib is not generally regarded as curative, given its favorable toxicity profile, most physicians favor its use as initial therapy for CML, with transplantation being reserved for those who fail to achieve a complete cytogenetic response with imatinib, relapse after an initial response, or are intolerant of the drug (Chap. 104). Allogeneic transplantation has been used to only a limited extent for chronic lymphocytic leukemia, in large part because of the chronic nature of the disease 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-related mortality has been substantial, and further follow-up is needed. Encouraging results have been seen using reduced intensity preparative regimens before allogeneic transplantation. Myelodysplasia Between 40 and 50% of patients with myelodysplasia appear to be cured with allogeneic transplantation. Results are better among younger patients and those with less-advanced disease. However, some patients with myelodysplasia can live for extended periods without intervention, and so transplantation is generally recommended only for patients with disease categorized as intermediate
risk I or greater according to the International Prognostic Scoring System (Chap. 102). Lymphoma Patients with disseminated intermediate- or high-grade non-Hodgkin's lymphoma who have not been cured by first-line chemotherapy and are transplanted in first relapse or second remission can still be cured in 40–50% of cases. This represents a clear advantage over results obtained with conventional- dose salvage chemotherapy. It is unsettled whether patients with high-risk disease benefit from transplantation in first remission. Most experts favor the use of autologous rather than allogeneic transplantation for patients with intermediate or high grade non-Hodgkin's lymphoma, because fewer complications occur with this approach and survival appears equivalent. For patients with recurrent disseminated indolent non-Hodgkin's lymphoma, autologous transplantation results in high response rates and improved progression-free survival compared to salvage chemotherapy. However, late relapses are seen after transplantation. The role of autologous transplantation in the initial treatment of patients is under study. Nonmyeloablative preparative regimens followed by allogeneic transplantation result in high response rates in patients with indolent lymphomas, but the exact role of this approach remains to be defined.
The role of transplantation in Hodgkin's disease is similar to that in intermediate- and high-grade non-Hodgkin's lymphoma. With transplantation, 5- year disease-free survival is 20–30% in patients who never achieve a first remission with standard chemotherapy and up to 70% for those transplanted in second remission. Transplantation has no defined role in first remission in Hodgkin's disease. Myeloma Patients with myeloma who have progressed on first-line therapy can sometimes benefit from allogeneic or autologous transplantation. Autologous transplantation has been studied as part of the initial therapy of patients, and both disease-free survival as well as overall survival were improved with this approach in randomized trials. The use of autologous transplantation followed by nonmyeloablative allogeneic transplantation has shown encouraging results. Solid Tumors Among women with metastatic breast cancer, 15–20% disease-free survival rates at 3 years have been reported, with better results seen in younger patients who have responded completely to standard-dose therapy before undergoing transplantation. Randomized trials have not shown superior survival for patients treated for metastatic disease with high-dose chemotherapy plus stem cell support. Randomized trials evaluating transplantation as treatment for primary breast
cancer have yielded mixed results. No role for autologous transplantation has been established in the treatment of breast cancer. Patients with testicular cancer who have failed first-line chemotherapy have been treated with autologous transplantation; ~10–20% of such patients apparently have been cured with this approach. The use of high-dose chemotherapy with autologous stem cell support is being studied for several other solid tumors, including ovarian cancer, small cell lung cancer, neuroblastoma, and pediatric sarcomas. As in most other settings, the best results have been obtained in patients with limited amounts of disease and where the remaining tumor remains sensitive to conventional-dose chemotherapy. Few randomized trials of transplantation in these diseases have been completed. Partial and complete responses have been reported following nonmyeloablative allogeneic transplantation for some solid tumors, most notably renal cell cancers. The GVT effect, well documented in the treatment of hematologic malignancies, may apply to selected solid tumors under certain circumstances. Posttransplant Relapse Patients who relapse following autologous transplantation sometimes respond to further chemotherapy, particularly if the remission following
transplantation was long. More options are available for patients who relapse following allogeneic transplantation. Of particular interest are the response rates seen with infusion of unirradiated donor lymphocytes. Complete responses in as many as 75% of patients with chronic myeloid leukemia, 40% in myelodysplasia, 25% in AML, and 15% in myeloma have been reported. Major complications of donor lymphocyte infusions include transient myelosuppression and the development of GVHD. These complications depend on the number of donor lymphocytes given and the schedule of infusions, with less GVHD seen with lower dose, fractionated schedules. Further Readings Appelbaum FR: Haematopoietic cell transplantation as immunotherapy. Nature 411:385, 2001 [PMID: 11357147] Baron F, Storb R: Hematopoietic stem cell transplantation after reduced- intensity conditioning for older adults with acute myeloid leukemia. Curr Opin Hematol 14:145, 2007 [PMID: 17255792] Bensinger WI et al: Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic
cancers. N Engl J Med 344:175, 2001 [PMID: 11172139] Copelan EA: Hematopoietic stem-cell transplantation. N Engl J Med 354:1813, 2006 [PMID: 16641398] Petersdorf EW et al: Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation. N Engl J Med 345:1794, 2001 [PMID: 11752355] Bibliography Child JA et al: High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 348:1875, 2003. [PMID: 12736280] Grunebaum Eet al: Bone marrow transplantation for severe combined immune deficiency. JAMA 295:508, 2006 [PMID: 16449616] Rubinstein P et al: Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 339:1565, 1998 [PMID: 9828244]
Schmitz N et al: Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: A randomized trial. Lancet 359:2065, 2002 [PMID: 12086759] Schouten HC et al: High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: Results from the randomized European CUP trial. J Clin Oncol 21:3918, 2003 [PMID: 14517188] Syrjala KL et al: Recovery and long-term function after hematopoietic cell transplantation for leukemia or lymphoma. JAMA 291:2335, 2004 [PMID: 15150205]