Treatment of Waldenström macroglobulinaemia – the experience of one centre
Authors:
Z. Adam; L. Pour; M. Krejčí; Z. Kořístek; M. Navrátil; A. Křivanová; L. Zahradová; R. Hájek
Authors‘ workplace:
Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. Jiří Vorlíček, CSc.
Published in:
Vnitř Lék 2009; 55(1): 9-17
Category:
Original Contributions
Overview
Waldenström macroglobulinaemia (WM) is adisease the incidence of which is approximately 10 times lower than that of multiple myeloma. The incidence of WM is reported to be respectively 0.34 per 100,000 men and 0.7 per 100,000 women. It is one of the less aggressive lymphoproliferative diseases in which therapy is indicated only when the disease symptoms start to manifest. We present aretrospective analysis of patients with the symptomatic form of WM who were treated with chemotherapy in our centre over the last 9 years, i.e. 19 WM patients (of which 7 women and 12 men). The median age upon diagnosis of the symptomatic form of WM and start of treatment was 59 (51–78) years. The median follow up for all patients was 31(7–121) months. The most frequent indication for WM treatment was anaemia in 57% (11/19), thrombocytopaenia in 21% (4/19), plasma hyperviscosity in 42% (8/19), symptomatic lymphadenopathy in 15% (3/19), and pathologic osteolysis in 15% (3/19) of cases, respectively. Decrease in immunoglobulin concentration under the lower physiological limit is not referred to as acharacteristic sign of WM, yet it was recorded in 7out of 19patients in our patient group and continued after chemotherapy, with the affected patients suffering from infections in remission more often than those with physiological values of immunoglobulins. 36% (7/19) patients were treated with R‑FC (rituximab+fludarabine+cyclophosphamide) therapy, 15% (3/19) with FC therapy, 15% (3/19) with R‑CHOP concluded by high‑dose chemotherapy with autologous transplantation in 1case, and 5% (1/19) with CHOP therapy. VAD (vancristine, ariamycine and dexamethasone) therapy was used in 10% (2/19) of patients and 10% (2/19) of patients were treated with oral chlorambucil. The first line of treatment achieved complete remission (CR) in 15% cases (3/15). Two patients who achieved CR were treated with R‑FC, and one patient with VAD. Partial remission (PR) was achieved by 63% of patients (12/19). Minor response (MR) was achieved by 10% (2/19), and stable disease (SD) was recorded in 10% of patients (2/19) after initial treatment. The first relaps of the disease was recorded in 5patients (2 of whom had PR and 3 MR) who achieved remission after additional lines of therapy. Thirteen patients are in the first PR. With afollow up median of 31months (7–121), only 2 patients died from other than the underlying disease. Additional malignant disease was diagnosed in 3 patients: 1colon carcinoma, 1acute myeloid leukaemia (AML) and 1myelodysplastic syndrome (MDS). All three received fludarabine and cyclophopsphamide as initial therapy. Of the three patients only the patient with MDS has survived and is now without any evidence of the presence of WM, i.e. in complete remission at 41months after the start of therapy. High‑dose chemotherapy with autologous transplantation was used in 2 cases, once as part of initial therapy and once as part of the therapy for the first relaps resistant to R‑CHOP chemotherapy. It is not possible to determine the median of the first remission or the median of total survival due to the short follow up interval.
Key words:
Waldenström macroglobulinaemia (Morbus Waldenström)– lymphoplasmacytic lymphoma– fludarabine– rituximab– myelodysplastic syndrome– acute myeloid leukaemia
Sources
1. Waldenström J. Incipient myelomatosis or essential hyperglobulinemia with fibrinogenopenia. A new syndrome? Acta Med Scand 1944; 117: 217–247.
2. Owen RG, Treon SP, Al-Katib A et al. Clinicopathological definition of Waldenström’s macroglobulinaemia. Consensus panel recommendation from the Second International Workshop on Waldenström’s macroglobulinemia. Semin Oncol 2003; 30: 567–584.
3. Desikan KR, Li Z, Jaganath S. Waldenströms makroglobulinemia: current therapy and future aproaches. BioDrugs 2002; 16: 201–207.
4. Klán J, Doležalová I, Pelíšková D et al. Waldenströmova makroglobulinémie jako model imunopatologie ve stáří. Geriatria 2004; 10: 18–27.
5. Klán J, Topinková E, Pelíšková D et al. Waldenströmova makroglobulinémie v geriatrické praxi. Čas Geriat Rev 2004; 2: 40–44.
6. Cerna M, Risik K, Jakubikova N. Lymfolazmocytoidní imunocytom – Waldenströmova choroba s postihnutím pluc. Stud Pneumol Phtiseol CS 1989; 49: 198–202.
7. Adam Z, Šmardová J, Ščudla V. Waldenströmova makroglobulinemie – klinické projevy, diferenciální diagnostika a prognóza nemoci. Vnitř Lék 2007; 53: 1325–1337.
8. Malý J, Tichý M, Blaha M et al. A case of acute Waldenström macroglobulinemia. Sbor Ved Praci Lék Fak Univ Karlovy Hrad Kr 1983; 26: 165–173.
9. Pozdechova A, Virsik K, Tichá M et al. Intrathorakalne prejavy Waldenströmovej makroglobulinémie. Stud Pneumol Phtiseol CS 1980; 40: 599–604.
10. Rencová E, Malý J, Bláha M et al. Dynamika sítnicových změn v závislosti na léčbě Waldenströmovy choroby. Čs Oftal 1993; 49: 3–7.
11. Schimonová M, Zatloukal P, Havlíček F et al. Amyloidóza plic při Waldenstromövě chorobě. Stud Pneumol Phtiseol 1998; 58: 72–74.
12. Wicklund MP, Kissel JT. Paraproteinemic neuropaty. Curr Treat Options Neurol 2001; 3: 147–156.
13. Weide R, Heymanns J, Koppler H. The polyneuropathy associated with Waldenström’s macroglobulinaemia can be treated effectively with chemotherapy and anti CD20 monoclonal antibody. Brit J Haematol 2000; 109: 838–841.
14. Gertz MA, Anagostopoulos A, Anderson K et al. Treatment recommendation in Waldström’s macroglobulinaemia. Consensus panel recommendation from the second international workshop on Waldenstöm’s macroglobulinaemia. Semin Oncol 2003; 30: 121–126.
15. Johnson SA, Birchall J, Luckie C et al. Guidelines on management of Waldenström’s macroglobulinemia. Brit J Haematol 2006; 132: 687–697.
16. Adam Z, Ščudla V, Krejčí M et al. Léčba Waldenströmovy makroglobulinemie a léčba nemocí způsobených monoklonálním gamaglobulinem. Vnitř Lék 2008; 54: 68–83.
17. Kimby E, Treon SP, Anagnastopoulos A et al. Update on recommendations for assessing response from the Third International Workshop on Waldenström’s macroglobulinaemia. Clin Lymphoma Myeloma 2006; 6: 380–383.
18. Weber D, Treon SP, Emmanouilides Ch et al. Uniform response criteria in Waldneström’s macroglobulinemia: Consensus panel recommendations from the second international workshop on Waldenström’s macroglobulinemia. Sem Oncol 2003; 30: 127–131.
19. Tichý M. Laboratorní analýza monoklonálních imunoglobulinů (paraproteinů). Český Těšín: Finidr 1997.
20. Ghobrial IR, Fonseca R, Gertz MA et al. Prognostic model for disease specific and overall mortality newly diagnosed symptomatic patients with Waldenström’s macroglobulinaemia. Brit J Haematol 2006; 133: 158–1654.
21. Weber DN, Dimopoulos MA, Dellasale J. 2-chlordeoxyadenosine alone and in combination for previsously untreated Waldenström’s macroglobulinaemia. Semin Oncol 2003; 30, 243–247.
22. Zinzani PL, Gherlinzon F, Bendandi M et al. Fludarabine treatment in resistent Waldenström’s macroglobulinemia. Eur J Haematol 1995; 54: 120–123.
23. Treon SP, Tournihac O, Branagan AR et al. Clinical response to sildenafil in Waldenstöm’s macroglobulinemia. Clin Lymphoma 2004; 5: 205–207.
24. Björkholm M. Treatment options in Waldenström’s macroglobulinemia. Clin Lymphoma 2004; 5: 155–162.
25. Treon SP, Gertz MA, Dimopoulos M et al. Update on treatment recommendations from the Third International Workshop on Waldenström’s macroglobulinaemia. Blood 2006; 107: 3442–3446.
26. Bowcock SJ, Rassam SM, Lim Z et al. High incidence of therapy releated myelodysplasia and acute leukemia in general hematology clinic patients treated with fludarabine and cyclophosphamide for indolent lymphoproliferative disorders. Brit J Haematol 2006; 134: 242–243.
27. Leleu Y, Manning R, Soumerai J et al. Increased incidence of disease transformation and development of MDS/AML in Waldenström’s macroglobulinemia patients treated with nucleoside analogs. Haematologica 2008 (Suppl 2); 95: abstr. WM3.10.
28. Ghobrial IR, Fonseca R, Greipp PR et al. Initial imunoglobulin M flare after rituximab therapy in patients diagnosed with Waldenström’s macroglobulinaemia. Cancer 2004; 101: 2593–2598.
29. Giudice I, Matutes E, Osuji N et al. Deleyed response to fludarabine in lymphoplasmocytic lymphoma/Waldenström’s macroglobulinemia. Hematologia 2005; 90: 268–270.
30. Anagnostopoulos A, Parameswaran N, Waleska HH et al. Autologous or allogeneic stem cell transplantation in patients with Waldenström’s macroglobulinemia. Biology Blood Marrow Transplant 2006; 12: 845–854.
31. Han PN. Autologous and allogeneic stem cell transplantation in patients with Waldenström’s macroglobulinemia. Biol Blood Marrow Transplant 2006; 12: 845–854.
32. Yang L, Wen B, Li H et al. Autologous peripheral stem cell transplantation for Waldenström’s macroglobulinemia. Bone Marrow Transplant 1999; 24: 929–930.
Labels
Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
2009 Issue 1
Most read in this issue
- Adrenal cancer
- Coronary artery ectasia and triple-vessel disease
- Treatment of Waldenström macroglobulinaemia – the experience of one centre
- Cardiovascular rehabilitation today