The American Society for Blood and Marrow Transplantation (ASBMT) grades its recommendations (1-6) and the quality of the supporting evidence (1-4). The definitions of these grades can be found at the end of the "Major Recommendations" field.
Recommendations for stem cell transplantation (SCT) as an effective therapy for multiple myeloma (MM) include the following:
- SCT is preferred to standard chemotherapy as de novo therapy.
- SCT is preferred as de novo rather than salvage therapy.
- Autologous peripheral blood stem cell transplantation (PBSCT) is preferred to bone marrow transplantation (BMT).
- Melphalan is preferred to melphalan plus total body irradiation as the conditioning regimen for autologous SCT.
Recommendations that SCT is not effective include the following:
Current purging techniques of bone marrow
Recommendations of equivalence include the following:
PBSCT using CD34+ selected or unselected stem cells.
No recommendation is made for indications or transplantation techniques that have not been adequately studied, including the following:
- SCT versus standard chemotherapy as salvage therapy
- Tandem autologous SCT
- Autologous or allogeneic SCT as a high-dose sequential regimen
- Allogeneic BMT versus PBSCT
- A preferred allogeneic myeloablative or nonmyeloablative conditioning regimen
- Maintenance therapy post–autologous SCT with interferon alpha
post-SCT
Table. Summary of Treatment Recommendations Made by the Expert Panel for Multiple Myeloma
| Indication for SCT |
Treatment Recommendation |
Highest Level of Evidence |
Reference* |
Comments |
| SCT vs. standard chemotherapy as de novo therapy |
1 |
1 |
Attal et al., 1996 |
Ongoing trials may change the recommendation. |
| SCT vs. standard chemotherapy as salvage therapy |
5 |
2 |
Alexanian et al., 1994 |
There is only 1 non-randomized study that applies. |
| SCT as de novo vs. salvage therapy |
2 |
1 |
Fermand et al., 1998 |
These are equivalent in terms of overall survival, however, SCT as de novo is preferred because it may avoid the inconvenience, cost, and risk of myelodysplasia from conventional alkylating
agent therapy. |
| Autologous vs. allogeneic SCT |
2 |
2 |
Lokhorst et al., 1999; Seiden et al., 1995; Anderson et al., 1993; Anderson et al., 1991; Björkstrand et al., 1996; Varterasian et al., 1997; Reynolds et al., 2001; Couban et al., 1997 |
Autologous SCT is recommended over a meyloablative allogeneic SCT. |
| Autologous PBSCT vs. BMT |
1 |
2, 3 |
Raje et al., 1997; Harousseau et al., 1995 |
PBSCT is preferred based on level 2 evidence regarding engraftment, not survival, outcomes.
PBSCT is also the accepted standard based on expert opinion.
|
| Autologous CD34+ selected vs. unselected PBSCT |
4 |
1 |
Stewart et al., 2001; Vescio et al., 1999 |
|
| Autologous purged BMT |
3 |
2 |
Reece et al., 1993; Lemoli et al., 1999; Rasmussen et al., 2002; Barbui et al., 2002 |
|
| Tandem autologous PBSCT |
6 |
4 |
|
A level 1 evidence study has been conducted and will soon be published to address this critical question. |
| Preferred autologous SCT myeloablative conditioning regimen |
1 |
1 |
Moreau et al., 2002 |
Mel is preferred to Mel plus TBI based on toxicity not efficacy, however, there is no level 1 evidence comparing Mel or Mel plus TBI with other conditioning regimens (eg, BuCy, BuMelTt). |
| Autologous high-dose sequential regimen |
6 |
4 |
Palumbo et al., 2000; Palumbo et al., 1997 |
|
| Allogeneic BMT vs. PBSCT |
6 |
2 |
Gahrton et al., 2001 |
|
| Preferred allogeneic SCT myeloablative conditioning regimen |
5 |
4 |
Cavo et al., 1998 |
There is only 1 feasibility study with a small sample size and no comparison group.
|
| Allogeneic SCT nonmyeloablative regimen |
5 |
4 |
Badros et al., 2002 |
There is only 1 feasibility study with a small sample size and no comparison group.
|
| Allogeneic high-dose sequential regimen |
6 |
|
|
No evidence. |
| Autologous SCT followed by allogeneic SCT |
5 |
|
|
No evidence published. A study is in progress to address this question. |
| Maintenance therapy post-autologous SCT with IFNa vs. none |
5 |
4 |
Cunningham et al., 1998 |
Early survival advantage (4-5 y) that is lost over time; problems with study methodology. |
| Maintenance therapy post-autologous SCT with IFNa vs. other therapies (i.e., corticosteroids, thalidomide, or its derivatives) |
5 |
|
|
No evidence. |
*The references listed represent the highest level of evidence used to make the treatment recommendation and are not inclusive of all evidence described in the review.
Abbreviations: SCT, stem cell transplantation; PBSCT, peripheral blood stem cell transplantation; BMT, bone marrow transplantation; Mel, melphalan; TBI, total body irradiation; IFNa, interferon alpha
Definitions:
Grading the Strength of the Treatment Recommendations
1
Effective treatment
2
Marginally effective treatment
3
Not an effective treatment
4
Equivalent treatments (no statistical or clinical difference between therapies)
5
Inadequately evaluated treatment and recommended for comparative study
6
Inadequately evaluated treatment but not recommended for comparative study
Grading the Quality of the Evidence
1
Evidence obtained from at least one properly randomized controlled trial
2-1
Evidence obtained from well-designated, controlled trials without
randomization
2-2
Evidence obtained from well-designated, cohort or case-controlled analytic studies, preferably from more than one center or research group
2-3
Evidence obtained from multiple timed series with or without the intervention, or from dramatic results in uncontrolled experiments
3
Opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees
4
Evidence inadequate owing to problems of methodology, e.g., sample size, length or comprehensiveness of follow-up, or conflict in evidence
