Multiple Myeloma, Tandem vs Second Transplants and Total Therapy – pro

Lay Summary: I review the current status of tandem versus second transplant and Total Therapy.

One needs to differentiate between tandem transplants, a planned sequence of two high dose treatments with HSCT salvage, and a second transplant, an approach of consolidating the first autologous HSCT with another HSCT ONLY if the first one appears partially effective.

A tandem autologous transplant, also known as a double autologous transplant, requires the patient to undergo two planned autologous stem cell transplants within 6 months. Stem cells are collected once before the initial transplant and half are used for each procedure. The followup transplant is performed after recovery from the first procedure whatever the results of the initial transplant. Tandem transplant is now NCCN recommended but only as 2a recommendation. On the other hand, for patients who have not responded completely, NCCN recommends second transplant.

Various strategies are being evaluated to improve the outcome of tandem transplants. One such strategy is intensification of therapy, such as that implemented in the Total Therapy program (see below), which is showing promising results. Another strategy is the incorporation of novel agents, such as thalidomide, Velcade, or Revlimid, into the treatment regimen either before or after transplant. A second transplant is an intensification approach.

Two hundred thirty-one patients with symptomatic myeloma were enrolled in Total Therapy I between 1990 and 1995 (Barlogie et al. Blood. 1997;89(3):789-793; Barlogie et al. Blood. 1999;93:55-65.) The Total Therapy I regimen included induction therapy with 3 cycles of VAD (vincristine, doxorubicin, dexamethasone). High-dose cyclophosphamide plus granulocyte-macrophage colony-stimulating factor (GM-CSF) was then used to mobilize stem cells prior to peripheral blood stem cell (PBSC) collection. After stem cell collection, EDAP (etoposide, dexamethasone, cytarabine, cisplatin) was given to enhance reduction of tumor cells prior to high-dose therapy (melphalan 200 mg/m²) and autologous transplant. The second course of high-dose therapy and transplant was performed 3 to 6 months later. Patients then received interferon maintenance until disease recurrence. There are now trials up to Total Therapy 5.
The final analysis of the landmark French IFM-94 trial demonstrated that double transplantation led to improved survival compared with single transplantation in patients with previously untreated myeloma. (Attal et al. N Engl J Med. 2003;349(26):2495-2502.) Boith of these studies suggested benefit; however, the benefits were not apparent for several years and the overall suvival remained a paltry 20% at 7 years.

Preliminary results of several randomized trials comparing tandem and single autologous transplants, which have not been followed as long, have also shown superior event-free survival with the tandem regimen in most studies. In one study (Bologna 96), significantly improved event-free survival with double transplants was seen among patients <60 years of age, particularly those who had not achieved a near CR after the first transplant. However, only the IFM-94 study has demonstrated improvement in overall survival with the tandem approach. The designs of these studies vary, so comparisons are difficult. In addition, it has yet to be determined which patients benefit most from a tandem transplant. It appears that in patients with poor prognostic features, outcome is not improved with tandem transplants, so additional strategies need to be evaluated in this patient population. Many of these studies are reviewed at

The issue of allogeneic after autologous transplant is reviewed under a separate heading.

Nordic –

Chemotherapy and stem-cell transplantation in patients with multiple myeloma: a practice guideline of the Cancer Care Ontario Practice Guidelines Initiative. Annals of Internal Medicine. 2002;136:619-629

Nordic –, Multiple Myeloma

Revised: 2/20/08

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