High-dose chemotherapy: Autologous bone marrow or peripheral stem cell transplantation
Evidence (high-dose chemotherapy: autologous bone marrow or peripheral stem cell transplantation):
The failure of conventional therapy to cure the disease has led investigators to test the effectiveness of much higher doses of drugs such as melphalan. The development of techniques for harvesting hemopoietic stem cells, from marrow aspirates or the peripheral blood of the patient, and infusing these cells to promote hemopoietic recovery made it possible for investigators to test very large doses of chemotherapy.
Based on the experience of treating thousands of patients in this way, it is possible to draw a few conclusions, including the following:
- The risk of early death caused by treatment-related toxic effects has been reduced to less than 3% in highly selected populations.
- Chemotherapy patients can now be treated as outpatients.
- Extensive prior chemotherapy, especially with alkylating agents, compromises marrow hemopoiesis and may make the harvesting of adequate numbers of hemopoietic stem cells impossible.
- Younger patients in good health tolerate high-dose therapy better than patients with a poor performance status.[81,82,83]
- Upon review of eight updated trials encompassing more than 3,100 patients, at 10 years' follow-up, there was a 10% to 35% event-free survival (EFS) rate and a 20% to 50% OS rate. New monoclonal gammopathies of an isotype (heavy and/or light chain) distinct from the original clone can emerge in long-term follow-up.
Single autologous bone marrow or peripheral stem cell transplantation
Evidence (single autologous bone marrow or peripheral stem cell transplantation):
While some prospective randomized trials, such as the U.S. Intergroup trial (SWOG-9321 [NCT00602641]), showed improved survival for patients who received autologous peripheral stem cell or bone marrow transplantation after induction chemotherapy versus chemotherapy alone,[86,87,88][Level of evidence: 1iiA] other trials have not shown any survival advantage.[89,90,91,92][Level of evidence: 1iiA]
Two meta-analyses of almost 3,000 patients showed no survival advantage.[93,94][Level of evidence: 1iiA]
Even the trials suggesting improved survival showed no signs of a slowing in the relapse rate or a plateau to suggest that any of these patients had been cured.[86,87,88,95] The role of ASCT has also been questioned with the advent of novel induction therapies with high complete-remission rates.[96,97]