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a survey on diagnostic methods and treatment
strategies used in patients with Waldenström's
macroglobulinaemia in the netherlands
S. Klodzinska1, J.M.I. Vos2, M.J. Kersten3, P. Wijermans4, M.C. Minnema1*
1Department of Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands, 2Department of Internal Medicine/Haematology, St. Antonius Hospital, Nieuwegein, the Netherlands, 3Department of Haematology, Academic Medical Centre, Amsterdam, the Netherlands, 4Department of Hematology, HagaHospital, The Hague, the Netherlands, *corresponding author: tel: +31 (0) 88-7557230, fax: +31 (0)88-7553741, e-mail: m.c.minnema@umcutrecht.nl a B s t r a C t
Background: Waldenström's macroglobulinaemia
addressed in clinical research and guidelines to improve (WM) is defined as a lymphoplasmacytic lymphoma care for WM patients in the Netherlands.
primarily located in the bone marrow, accompanied by an immunoglobulin M (IgM) monoclonal protein in the serum. The symptoms are highly variable, which K e y W o r d s
can sometimes lead to a diagnostic delay. Currently, there is a wide range of therapeutic options used for the Waldenström's macroglobulinaemia, M-protein, immuno- management of WM but no approved therapeutic agents are available specifically for this disease.
Methods: An online survey was prepared and sent out to haematologists and haemato-oncologists in the Netherlands, together with an invitational letter to participate. Information was gathered about the preferred Waldenström's macroglobulinaemia (WM) is a methods of diagnosing and treating patients with WM in non-Hodgkin's lymphoma, characterised by infiltration general, and about the last WM patient diagnosed in their of the bone marrow with small lymphocytes, lymphoplasmacytic cells and plasma cells, accompanied Results: 83 (31.8%) responses were obtained, out of which by secretion of monoclonal immunoglobulin M (IgM) 68 (81.9%) contained responses to all three parts of the protein in the serum.1 WM is a rare disease, with an survey. The respondents most commonly used either overall incidence of approximately 3 per million people rituximab-CVP or chlorambucil as first-line treatment, per year and about 75-100 newly diagnosed patients in the whereas rituximab in combination with purine analogues Netherlands per year. The clinical presentation is variable was the most frequently applied second-line treatment. among patients, and around 30% of WM patients are The prevention of an IgM ‘flare' was managed by the asymptomatic and do not require therapy at diagnosis.2 respondents in various ways, and rituximab maintenance According to current standards, treatment should be treatment was not commonly used. initiated only when lymphoma-related clinical symptoms Conclusion: This survey indicates that in general the or at least one of the following parameters are present: diagnostic methods and treatment options for WM haemoglobin <6.2 mmol/l, platelets <100 x 109/l, are well known to a representative number of Dutch significant organomegaly or adenopathy, hyperviscosity, haematologists. The areas of uncertainty are knowledge cryoglobulinaemia, cold agglutinin disease or amyloidosis.3 about asymptomatic vs symptomatic disease, risk of Until recently, no treatment recommendations were hyperviscosity in relation to IgM level, and the occurrence available for WM patients in the Netherlands. Even and prevention of an IgM ‘flare'. These issues should be internationally, there is no consensus on the standard of Van Zuiden Communications B.V. All rights reserved.
first-line treatment.4 Additionally, there are no approved Basic information about the physician and the hospital
therapeutic agents specifically for this disease. The The single largest group of respondents was between drugs used most often are alkylating agents, such as age 45 and 55 (44.6%), and 62.7% of the respondents chlorambucil and cyclophosphamide, purine analogues, were 45 years or older. Most worked at an academic rituximab and corticosteroids. Many aspects must be taken hospital (38.6%) or at a HOVON level C (31.3%) hospital, into account when deciding on a certain treatment regimen which represents hospitals equipped to give intensive for a WM patient, which may be recognised as quite a treatment. Out of the ten referral regions, the responses complex process by practising clinicians. were mostly gathered from haematologists based in the In order to examine the currently used diagnostic and VU University Medical Center and Isala region (18.1%), therapeutic management of patients with WM, a survey University Medical Centre Nijmegen St Radboud region was carried out amongst Dutch haematologists and (16.9%), University Hospital Maastricht region (15.7%) and haemato-oncologists, investigating the strategies used in the Erasmus Medical Centre (15.7%). Most of the diagnostic general as well as the specific methods used in their last tools, including CT scan, protein electrophoresis and bone patient diagnosed with WM.
marrow morphology and histology were readily available in all Dutch hospitals. Tests for cryoglobulins and cold agglutinins were available to 94 and 92% of respondents respectively. Tests with low availability were serum blood viscosity measurement and anti-MAG antibody titre test, An online questionnaire in Dutch containing 24 questions available to 7.5% and 5.6% of respondents respectively.
was prepared, and a link to this survey was sent out to all known haematologists and haemato-oncologists in diagnostic methods used in patients with WM
the Netherlands (n=261) (see Appendix). A reminder was The most frequently used diagnostic methods are the sent after one month. The questionnaires were answered level of the M-protein in the serum as assessed by protein electrophoresis (88%), bone marrow biopsy with In the first part of the survey, physicians were asked immunohistochemistry (84.3%), bone marrow aspirate questions relating to the type of hospital (HOVON level, morphology (77.1%), serum total IgM level (73.5%) and multiparameter flow cytometry of the bone marrow they work at and the consultation region it belongs to, as aspirate (72.3%) ( figure 1). Furthermore, 43.4% of well as the availability of various diagnostic methods. respondents reported use of the free light chains (FLC) HOVON level A hospitals are academic hospitals equipped assay. Imaging techniques were less commonly applied, a to perform both allogeneic and autologous stem cell CT scan was selected by 60.2% of respondents, followed transplants (SCTs). Level B and C hospitals may administer intensive therapy, for example treatment of acute leukaemia, but only level B hospitals perform autologous SCTs, and level D hospitals do not treat patients requiring figure 1. Which diagnostic methods do you use to
intensive haematological care.
diagnose WM? In the second part the questions were focused on the preferred diagnostic methods for diagnosing WM and the line of treatment preferred for newly diagnosed as well as relapsed patients. In the third part, physicians were asked about their last patient diagnosed with WM, the symptoms that led to the suspicion of WM, the therapeutic management of that patient and the time before a response was detected. Most answers were multiple choice and more than one answer was possible if appropriate. Ultrasound of the abdomen Eighty-three surveys (31.8% of total) were completed, Morphology of bone cytometry; bone ….
Multiparameter flow Quantitative IgM leve out of which 15 (18.1% of responses) were incomplete, because the questions in the third part of the survey were Commonly used diagnostic methods in dutch hospitals for diagnosing
left unanswered. All of the percentages are given as a WM. More than one answer was possible. numbers are given as absolute
percentage of respondents who answered the question.
value of the responses received.
Vos et al. Waldenström's macroglobulinaemia in the Netherlands.
by chest X-ray and ultrasound of the abdomen, chosen (1.2%) and an autologous stem cell transplant (4.8%) were by 32.5% and 28.9% of respondents, respectively. An all indicated as possible second-line treatments ( figure 2). FDG-PET scan was used by only 4.8% of respondents. Respondents indicated on average two (range 1-8) possible For diagnosing and staging of WM a combination of tests options for second-line treatment. is necessary and the respondents used on average seven Subsequently, respondents were asked about any diagnostic methods (range 2-9). One respondent chose a precautionary actions used to reduce the risk of combination of only two diagnostic methods but no one hyperviscosity syndrome due to an IgM ‘flare' reaction opted for only one diagnostic method. when treating patients with rituximab. Twenty-one of the Although demonstrating the presence of monoclonal IgM respondents (29.6%) did not use any preventive actions, M-protein is essential for the diagnosis of WM, it was not whereas 22 (31%) stated that as a precautionary measure chosen by 12% of respondents. We looked whether these they avoided using rituximab in the first treatment cycle. respondents chose the total IgM level as an alternative test, The remaining 28 (39.4%) of the respondents stated that in but this was not the case.
some cases they would use plasmapheresis before starting treatment or do not use rituximab in the first treatment treatment preferences in patients with WM
cycle. As a follow-up question respondents were asked Two treatment options were preferred in the first line: at which level of M-protein or IgM they would apply this rituximab-CVP (cyclophosphamide, vincristine, strategy. The mean reported level was 40 g/l with a range prednisone) in 26 (36.1%) of the respondents, and from 20 g/l up to >90g/l (n=15).
rituximab in combination with other alkylating agents When asked about the use of maintenance therapy 52 in 24 (33.3%) ( figure 2). In total, 81.9% of the respondents (74.3%) of the respondents answered that maintenance chose a combination of rituximab and chemotherapy therapy is not indicated, whereas 16 (22.9%) of the as the preferred first line of treatment. Monotherapy respondents indicated rituximab as best maintenance with an alkylating agent was the preferred first-line therapy. One respondent indicated bortezomib and one treatment in only 10 (13.9%) of the respondents. None respondent indicated thalidomide as best option.
of the respondents indicated rituximab monotherapy, The next series of questions concerned the symptoms bortezomib, bendamustine or thalidomide as their which prompted the start of treatment in patients recommended first line of treatment. previously diagnosed as asymptomatic. Multiple answers As preferred second-line treatment, respondents indicated were possible and the most frequent were anaemia (85.5%), the use of rituximab in combination with purine analogues symptoms of hyperviscosity (84.3%) and occurrence of B (55.4%). Additionally, rituximab monotherapy (9.6%), symptoms (79.5%) (figure 3). Nineteen respondents (22.9%) bortezomib (18.1%), bendamustine (21.7%), thalidomide reported that a specific level of M-protein or IgM was the figure 2. Which of the given treatment options do you prefer as a first and second line of treatment?
First line of treatmentSecond line of treatment Alkylating agents alkylating agents Preferred first and second line of treatment for WM. More than one answer was possible. numbers are given as absolute value of the responses
received.

Vos et al. Waldenström's macroglobulinaemia in the Netherlands.
figure 3. Variables evaluated in follow up of
progression by increase in the level of IgM or M-protein' (16.2%) and ‘development of B symptoms'(9.9%). Ten respondents (15.4%) stated that they began treatment as soon as the patient was diagnosed. The most commonly used first-line therapy to treat the last patient with WM was R-CVP (33.3%). Alkylating agents such as chlorambucil were also commonly used (30.3%). In total, 56% of respondents used rituximab in combination with any chemotherapy, while 4 (6%) gave rituximab monotherapy as first-line treatment to their last patient. Furthermore, respondents choosing a combination of rituximab and chemotherapy as first-line treatment also more often reported (59.5%) that the patient responded to the treatment (defined as a >25% decrease in the M-protein level) within three months of the initiation of treatment, B-symptom r, weight, …) hepato- or ….
compared with the other first-line treatment options A specific level of IgM or M protein (41.7%). In general, the maximum response was reported to occur in the first part of treatment (cycle 1 to 3-4) in 17 Variables evaluated in follow up of asymptomatic patients. More than
one answer was possible. numbers are given as absolute value of the

patients (30.4%), in the last part of treatment (cycles 3-4 to responses received.
6-8) in 27 patients (48.2%), and after stopping treatment in12 patients (21.4%). In 38 patients (64.4%) second-line treatment had not yet been necessary, in 14 (23.7%) second-line therapy was started between 1 and 4 years main reason to start treatment, at a median M-protein level after first-line therapy and in 4 (6%) patients after 4 years. of 30 g/l (range 20 - >60g/l).
Three patients (5.1%) needed second line of treatment within one year of the last dose of the first-line treatment. Most recent experience with diagnosis and treatment of a
Five respondents (8.5%) reported that they used rituximab WM patient
maintenance therapy for their last patient.
To this section 68 responses (81.9% of all responses) were gathered. The questions concerned the number of patients the respondents currently have under observation or treatment, and the diagnostic and treatment methods which were used on their last patient with WM. The survey had a response rate of 31.8%. Responses Twenty-five (36.8%) respondents stated that they currently were evenly spread among all of the ten haematological have 5-8 patients with WM on follow-up or under consultation regions in the Netherlands. The majority treatment, whereas 20 (29.4%) stated that they have more of respondents were experienced haematologists, but than 8 patients. Twenty respondents (29.4%) have between selection bias is of course always present in this type of 2 and 4 patients and the remaining 3 (4.4%) respondents research. Respondents may be haematologists with a stated that they have 1 or no patients under control or specific interest in WM and answers may be partly guessed treatment. When asked about the number of patients due to lack of memory of details or answers may be given actively being treated the most frequent response was 0-1 that are the ‘expected correct' answers instead of reflecting patient (48.5%) or 2-4 patients (45.6%). The age of the daily practice.
last treated patient was ‘between 60 and 70' in 39.7% and Many of the diagnostic methods important for the ‘more than 70 years of age' in 38.2% of the respondents. diagnosis of WM are easily accessible in Dutch hospitals. Only 4 respondents (5.6%) indicated that the age of the last As expected, most respondents use a combination of tests patient was less than 50 years. to confirm the diagnosis. The five methods used most The most common symptoms leading to the diagnosis frequently were blood tests assessing the M-protein and of WM in their last treated patient were anaemia (51.8%) total IgM levels, bone marrow biopsy with immunohisto- and weakness and fatigue (15.9%) and many respondents chemistry, as well as multiparameter flow cytometry and selected both answers.
morphology of the bone marrow aspirate. Surprisingly, Anaemia was also the most frequently indicated reason to many respondents (72.3%) chose multiparameter flow start treatment in 43 (52.9%) of cases. Other indications for cytometry as one of the diagnostic methods, which is the start of therapy included ‘evidence of problems caused indeed very helpful but is not mentioned in international by the M-protein'(29.4%) as well as ‘evidence of disease guidelines as a required test.5 The FLC assay was chosen Vos et al. Waldenström's macroglobulinaemia in the Netherlands.
by 43.4% of the respondents, although this method has not indication of uncertainty and the need for more defined shown to have additive value in patients with WM. guidelines to prevent an IgM ‘flare'.
The preferred first line of treatment according to most Indications for starting treatment were mostly aneamia, respondents (81.9%) was immunochemotherapy. Although symptoms of hyperviscosity and B symptoms, such as rituximab is registered for treatment of non-Hodgkin weakness, fatigue, weight loss and anorexia. Nineteen lymphomas (NHL), it is not registered specifically for WM (22.9%) of the respondents stated that they initiate treatment. Since WM is considered a type of NHL, and treatment when a certain level of IgM or M-protein is effectiveness has been shown in one randomised trial, present, usually between 30g/l and 50 g/l. In general, the its use has become common practice.6 However, when level of IgM or M-protein itself is not an indication for asked for first-line treatment used in their last diagnosed treatment initiation, unless symptoms of hyperviscosity patient only 56% had prescribed immunochemotherapy, and chlorambucil monotherapy was still used in 30% of The last part of the survey asked about personal experience the patients. This discrepancy might reflect transition of with WM patients. As expected for an indolent disease, treatment preferences in the last years, comorbidity of the most patients were not receiving active treatment (‘wait and last treated patient, difference between daily practice and see' policy) and were older than 60 years. The majority of given ‘expected' answers or it may be due to the fact that respondents did not have many patients in their practice less haematologists responded to the last part of the survey.
which may imply they have limited experience in treating When deciding on a second-line treatment, many WM patients. When deciding on treatment initiation, the respondents indicated that several options were possible. most important symptoms were anaemia, development Rituximab in combination with purine analogues was the of symptoms of hyperviscosity and progression of disease preferred second line of treatment (55.4%), and additionally although an increase in IgM or M-protein levels was also R-CVP, bendamustine, bortezomib and rituximab monotherapy were chosen. Rituximab maintenance Because WM is a disease in which treatment responses therapy is seldom applied but a recent retrospective are often delayed, respondents were asked what their analysis suggests that it may also be beneficial in experience was with time to first response. Combinations WM patients.7 Results of an ongoing randomised trial of rituximab and chemotherapy seem to induce the fastest performed by the Studiengruppe Indolente Lymphome in responses. In about 20% of patients responses were Germany are eagerly awaited.
only obtained after treatment was stopped. This is also a Subsequently, the respondents were asked about the well-known phenomenon: responses occurring until one precautions taken to prevent an IgM ‘flare' reaction year after the end of treatment have been reported and this when a rituximab-containing treatment was started. may be due to longer survival of the clonal plasma cells, The IgM ‘flare' is the occurrence of an initial increase in which produce the M-protein, after anti B-cell directed the IgM level that usually occurs within 15-30 days after initiation of treatment which can cause hyperviscosity syndrome in patients who already had a high IgM level.8 The increased level of IgM can remain elevated C o n C l U s i o n
for three to four months and is not an indication of treatment failure. The IgM ‘flare' arises in approximately Most oncologists and haematologists participating in this half of the WM patients treated with rituximab survey showed excellent understanding of the diagnostic monotherapy, and is generally seen less frequently when methods and treatment options in WM. The level of rituximab is combined with fast-acting chemotherapy M-protein at which symptoms may be expected is always such as fludarabine or bortezomib.9,10 In the DRC a subjective clinical judgement and some physicians wait (Dexamethasone-Cyclophosphamide-Rituximab) trial, in until symptoms occur while others start treatment if IgM which no preventive actions were taken, an IgM ‘flare' levels increase. The areas of uncertainty mostly concern was observed in 32% of patients, and 11% experienced an the risk of hyperviscosity and its relationship with IgM >25% IgM increase.11 However, this did not lead to signs levels, and the occurrence and prevention of IgM ‘flare'. or symptoms of hyperviscosity syndrome in any of the These issues, among others, are addressed in the Dutch patients. Respondents were given three possible options guidelines for WM, which are published in this same and had a slight preference to select patients in whom issue of the Netherlands Journal of Medicine and hopefully they would omit rituximab in the first cycle and/or use will contribute to improved care for WM patients in the plasmapheresis. As a follow-up question, the last group of respondents were asked at which level of IgM they would take preventive measures, which varied from >20g/l up Grants or conflict of interest: none reported to >90g/l. This disparity in the responses might be an Vos et al. Waldenström's macroglobulinaemia in the Netherlands.
r e f e r e n C e s
7. Treon SP, Hanzis C, Manning RJ, et al. Maintenance Rituximab is associated with improved clinical outcome in rituximab naive patients with Waldenstrom Macroglobulinaemia who respond to a rituximab-containing regimen. Br J Haematol. 2011;154:357-62.
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2. Gertz MA, Fonseca R, Rajkumar SV. Waldenstrom's macroglobulinemia. 9. Dhodapkar MV, Jacobson JL, Gertz MA, et al. Prognostic factors and response to fludarabine therapy in patients with Waldenstrom macroglob- 3. Kyle RA, Treon SP, Alexanian R, et al. Prognostic markers and criteria ulinemia: results of United States intergroup trial (Southwest Oncology to initiate therapy in Waldenstrom's macroglobulinemia: consensus Group S9003). Blood. 2001;98:41-8.
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recommendations from the Third International Workshop on Waldenstrom's macroglobulinemia. Blood. 2006;107:3442-6.
11. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, et al. Primary treatment of Waldenstrom macroglobulinemia with dexamethasone, 5. Kimby E, Treon SP, Anagnostopoulos A, et al. Update on rituximab, and cyclophosphamide. J Clin Oncol. 2007;25:3344-9.
recommendations for assessing response from the Third International Workshop on Waldenstrom's Macroglobulinemia. Clin Lymphoma 12. Vos JMI, Minnema MC, Wijermans PW, et al. Guideline for diagnosis and treatment of Waldenström's macroglobulinaemia. Neth J Me. 2013:71:54-62.
6. Buske C, Hoster E, Dreyling M, et al. The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Leukemia. 2009;23:153-61.
a P P e n d i x
a survey on diagnostic methods and treatment strategies used in patients with Waldenström's macroglobulinaemia
Basic information about the haematologist and the type of work Diagnosis and treatment of Waldenström's macroglobulinaemia 5. Which diagnostic tools do you use to diagnose WM? (multiple 1. What is your age? answers possible) a. Younger than 25 e. Between 40 and 45 a. Ultrasound of the abdomen g. Multiparameter flow b. Between 25 and 30 f. Between 45 and 50 cytometry of bone marrow c. Between 30 and 35 g. Between 50 and 55 d. Between 35 and 40 h. Blood tests to determine IgM e. Bone marrow biopsy with 2. What is the HOVON level (‘Echelon') of your hospital? i. Blood tests to determine f. Morphology of bone marrow M-protein levels j. Serum free light chain assay k. Other, namely… 3. In the Netherlands the haematological care is organised around 10 consultation centres. Which one is your consulta- 6. What is, in your opinion, the preferred first-line treatment for symptomatic WM patients? b. UMCN St Radboud b. Alkylating agents such as g. DRC regimen (dexa- cyclophosphamide and methasone, rituximab, c. Purine analogues such as h. Bortezomib (in combination) fludarabine and cladribine i. Bendamustine (in 4. Which diagnostic methods are available in your hospital? d. Rituximab in combination (multiple answers possible) with alkylating agents j. Thalidomide (in f. Serum free light chain assay e. Rituximab in combination g. Viscosity measurement with purine analogues k. Other, namely… c. Multiparameter flow h. Cryoglobulin analysis 7. The administration of rituximab is associated with an ‘IgM d. Total IgM levels i. Cold agglutinin test flare' in 50% of the patients. Do you take precautionary e. Total M protein levels j. Anti-MAG antibodies test a. No, the IgM flare rarely c. In some cases I take precau- tionary measures such as b. Yes, in the first cycle I do not plasmapheresis or I give the first cycle without rituximab Vos et al. Waldenström's macroglobulinaemia in the Netherlands.
8. If your answer to question 7 was ‘In some cases I take precau- 18.When did you start treatment? (multiple answers possible) tionary measures such as plasmapheresis or I give the first a. As soon as the patient was d. As soon as development of cycle without rituximab': at what level of IgM protein do you B-symptoms occurred decide to take precautionary measures? (give your answer in b. As soon as there was evidence of problems caused f. Not applicable, no treatment by the M protein (hypervis- 9. If you decide to follow a wait-and-see policy (no treatment), cosity, neuropathy, amyloido- g. Other, namely… which of these diagnostic results are an indication for you to sis, cryoglobulinaemia) start treatment? (multiple answers possible) c. As soon as there was a. A certain level of IgM or M f. Development of evidence of disease progres- sion caused by a rise in the M b. Anaemia or other g. Development of splenomeg- protein or IgM levels c. Symptoms of hyperviscosity aly or hepatomegaly h. Other, namely… 19.What was the first-line treatment that you used in this patient? e. Progression of g. DRC regimen (dexa- b. Alkylating agents such as methasone, rituximab, cyclophosphamide and cyclophosphamide) 10.If your answer to question 9 was : ‘A certain level of IgM or M h. Bortezomib (in combination) protein': what level of IgM or M protein is important for you to c. Purine analogues such as i. Bendamustine (in start the treatment? (give your answer in g/l)… fludarabine and cladribine d. Rituximab in combination j. Thalidomide (in 11. What do you think are preferred second-line treatments? with alkylating agents (multiple answers possible) e. Rituximab in combination k. Autologous stem cell g. DRC regimen (dexa- with purine analogues b. Alkylating agents such as methasone, rituximab, l. Other, namely… cyclophosphamide and cyclophosphamide) h. Bortezomib (in combination) 20.How soon after the start of treatment did the patients show a c. Purine analogues such as i. Bendamustine (in response (defined as >25% reduction in M-protein levels)? fludarabine and cladribine a. Less than 3 months c. Between 6 months and 1 year d. Rituximab in combination j. Thalidomide (in b. Between 3 and 6 months d. No response to first line of with alkylating agents e. Rituximab in combination k. Autologous stem cell with purine analogues 21.When was the maximum (best) response achieved? l. Other, namely… a. In the first part of the c. After the treatment was treatment (cycle 1 to 3-4) 12.What do you think is the best maintenance therapy? b. In the last part of the d. Insufficient or no response, treatment (cycles 3-4 to 6-8) switched to another e. Other, namely… treatment, namely… 22.How long after the last dose of the first-line treatment did you Most recent experience with the diagnosis and treatment of a patient begin with second-line treatment? with Waldenström's macroglobulinaemia a. Second line of treatment was c. Between 1 and 2 years d. Between 2-4 years 13.Do you treat patients with WM in your clinic? b. Less than 1 year e. More than 4 years 23.If applicable, what was the second line of treatment that you 14.How many patients are you currently seeing (follow-up and in a. Not applicable h. DRC regimen (dexa- c. Alkylating agents such as methasone, rituximab, cyclophosphamide and cyclophosphamide) 15.How many patients are you currently treating? i. Bortezomib (in combination) d. Purine analogues such as j. Bendamustine (in fludarabine and cladribine e. Rituximab in combination k. Thalidomide (in 16.What was the age of the last patient with WM that you treated? with alkylating agents a. Less than 50 years c. Between 60 and 70 f. Rituximab in combination l. Autologous stem cell b. Between 50 and 60 d. More than 70 years with purine analogues m.Other, namely… 17.What was/were the first symptom(s) of this patient, which resulted in the diagnosis of WM? (multiple answers possible) 24.Did you use maintenance treatment in this patient? a. None, patient was g. Lymphadenopathy a. Yes, in the first line, and I e. Yes, in the second line, and I b. Weakness and fatigue b. Yes, in the first line, and I f. Yes, in the second line, and I used thalidomide d. Weight loss and/or anorexia k. Vasculitis/skin lesions c. Yes, in the first line, and I used thalidomide h. Other, namely… f. Elevated erythrocyte sedi- m.Other, namely… d. Yes, in the second line, and I Vos et al. Waldenström's macroglobulinaemia in the Netherlands.

Source: http://waldenstrom.eu/documenten/newsletter/2013-03-28_Minnema_Survey_WM_in_NL.pdf

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A. Les McDonald, Founding CNAC Executive Director (Editor's Note: The following article appeared in the Globe & Mail "Lives Lived" section on April 3, 2008. It waswritten by Les' good friend, Ron Jette. I am pleased to share it with you. It's hard for me to believe it has already beensix months. Ron really captured Les' spirit and made me hear my good friend's laugh one more time.Thanks Ron. – Cheryl)

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CURRICULUM VITAE TERRI ELIZABETH WEAVER, PH.D., RN, FAAN BUSINESS ADDRESS HOME ADDRESS University of Illinois at Chicago - College of Nursing 814 Franklin Avenue River Forest, IL 60305 Chicago, IL 60612-7350 708/771/5623 (home) 312/919/5978 (cell) 610-293-4598 (fax) Penntw@yahoo.com 312/413/4399 (fax)