The levels of evidence (I–IV) and strength of evidence (A–C) supporting the recommendations are defined at the end of the "Major Recommendations" field.
Plasma Exchange
- 1-2 procedures, exchanging 1-1½ calculated plasma volumes is advised for the treatment of hyperviscosity syndrome (HVS) in Waldenström's macroglobulinaemia (WM). In patients who are drug resistant this may be indicated as long term management. Level of evidence III, Grade of recommendation B.
Neuropathies
- The evidence supporting plasma exchange for the treatment of peripheral neuropathy associated with an IgM paraprotein is weak. Level of evidence III-IV, Grade of recommendation C.
Cryoglobulinaemia
- Although there are few studies, which consider the role of plasma exchange in the treatment of cryoglobulinaemia, there is a clear rationale for its use. Level of evidence III-IV, Grade of recommendation C. The treatment room should be warm and blood warmers used in the cell separator circuit to prevent precipitation during the procedure.
Combination Chemotherapy
- Alkylating-agent based therapy is appropriate for the initial and subsequent treatment of Waldenstrom's Macroglobulinaemia. Level of evidence IIa, Grade of recommendation B.
Purine Analogues
- Purine analogues are appropriate for the initial and subsequent treatment of Waldenstrom's Macroglobulinaemia. There is no consensus on the duration of treatment with cladribine or fludarabine, or on which purine analogue is superior. Level of Evidence IIa, Recommendation B. Fludarabine is more active than cyclophosphamide, doxorubicin and prednisolone (CAP) as salvage therapy, Level of Evidence Ib, Grade of recommendation A.
Other Treatments
- Rituximab is active in the treatment of WM but associated with the risk of transient exacerbation of clinical effects of the disease and should only be used with caution especially in patients with symptoms of hyperviscosity and/or IgM levels > 40g/L. Level of evidence IIb, Grade of recommendation B.
- Thalidomide is of potential use in the treatment of patients who have previously received alkylating agents, purine analogues and antibody therapy. Other agents are currently only recommended in the context of clinical trials. Level of evidence III, Grade of recommendation B.
High Dose Therapy
- High dose therapy supported by autologous stem-cell transplantation has a role in the management of selected patients with WM with primary refractory or relapsed disease. Level of evidence III, Grade of recommendation B.
Definitions:
Levels of Evidence
Ia Evidence obtained from meta-analysis of randomised controlled trials
Ib Evidence obtained from at least one randomised controlled trial
IIa Evidence obtained from at least one well designed controlled study without randomisation
IIb Evidence obtained from at least one other type of well designed quasi-experimental study
III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case control studies.
IV Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities.
Grades of Recommendations
Grade A
Evidence level Ia and Ib
Required – at least one randomised controlled trial as part of the body of literature of overall good quality and consistency addressing specific recommendation
Grade B
Evidence levels IIa, IIb, and III
Required – availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendation.
Grade C
Evidence level IV
Required – evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities. Indicates absence of directly applicable clinical studies of good quality
