Autologous Stem Cell Transplantation as a Care Option in Waldenstrom's Macroglobulinemia

Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72205-7199, USA.
Clinical lymphoma, myeloma & leukemia (Impact Factor: 2.02). 02/2011; 11(1):139-42. DOI: 10.3816/CLML.2011.n.032
Source: PubMed


The optimal management of Waldenstrom's macroglobulinemia (WM) is in evolution, especially since the introduction of novel agents for its sister disease, multiple myeloma. Literature on the utility of autologous stem cell transplantation (ASCT) in WM, albeit mostly retrospective, supports its efficacy for symptomatic disease in eligible patients. Here, we present the experience of managing WM at our single institution. We report that ASCT improved OS/EFS in both treatment-naive and previously treated WM patients. Elevated LDH emerged as a poor prognostic factor in both univariate and multivariate analyses. Based on these data and other series of autologous SCT experience, it may be feasible to employ this strategy upfront in transplant eligible WM patients when they require a therapeutic intervention for symptomatic disease.

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    • "Autologous stem cell transplantation produces durable responses with a low treatment-related mortality rate (Kyriakou et al, 2010; Usmani et al, 2011). Although no randomized clinical trials have addressed autologous stem cell transplantation in the first-line setting, it may be considered in transplant-eligible patients with high WM stage and increased lactate dehydrogenase level (i.e, patients with highrisk disease) (Bachanova & Burns, 2012). "
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    ABSTRACT: In this review, the key issues that pertain to Waldenström disease are discussed in a concise question-and-answer format. Diagnosis, prognosis, and indications for state-of-the-art therapy are updated. Current therapies presented at the 7th International Workshop for Waldenström Macroglobulinaemia are included.
    British Journal of Haematology 05/2013; 162(3). DOI:10.1111/bjh.12367 · 4.71 Impact Factor
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    ABSTRACT: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. The presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. Age, hemoglobin level, platelet count, β2 microglobulin, and monoclonal IgM concentrations are characteristics required for prognosis. Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-based therapy is used in virtually all US patients with WM and can be combined with alkylating agent or purine nucleoside analog (or both). The preferred Mayo Clinic nonstudy therapeutic induction is rituximab, cyclophosphamide, and dexamethasone. Future stem cell transplantation should be considered in induction therapy selection. Bortezomib, thalidomide, everolimus, lenalidomide, and bendamustine have all been shown to have activity in WM. Given WM's natural history, reduction of complications will be a priority for future treatment trials. Am. J. Hematol. 88:703–711, 2013.
    American Journal of Hematology 05/2012; 87(5):503-10. DOI:10.1002/ajh.23192 · 3.80 Impact Factor
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    ABSTRACT: Acquired autoimmune haemolytic anaemia is divided according to the characteristics of immunoglobulin causing haemolysis. The most frequent are haemolytic anaemia with thermal antibodies. They bind to erythrocytes and initiate their destruction in the reticuloendothelial system cells, leading to extravascular haemolysis. Cold agglutinin disease differs significantly from haemolytic anaemia with thermal antibodies. Agglutination is caused by monoclonal antibodies, in most cases class IgM and very rarely class IgG. Under cold conditions they bind to erythrocytes and cause their agglutination and subsequent disorder of blood circulation in body parts with a lower temperature. Agglutinins binding initiate the binding of the complement to the erythrocytes. Under warm conditions the binding becomes loose but the parts of the complement, which are already bound, cause haemolysis, which is mainly of an intravascular nature. The loose haemoglobin causes haemoglobinuria. Description of a patient with the disease. The 1st symptoms of the disease, i.e. anaemia + circulatory disorders in the acral parts of the body, disappearing under warm conditions followed with haemoglobinuria, led to the dia-gnosis of cold agglutinin disease. The 1st line treatment, prednison, did not show any response. The 2nd line treatment used was rituximab and dexametazon. Rituximab was administered in doses of 500 mg/ m2 to 4 times in a row in weekly intervals. Dexametazon was administered in doses of 40 mg from 1st to 4th day and from 15th to 18th day of the cycle. This treatment, however, did not show any response either. Therefore this article brings an overview of all publications regarding the disease treatment with the aim of choosing the most effective treatment options in the case of failure of the monotherapy using rituximab. The 1st line treatment for cold agglutinin disease is rituximab in monotherapy, usually administered once per week at least for 4 weeks. This treatment shows a response in about one half of treated patients and the remission duration median after rituximab administration is 11 months. A combination of rituximab with fludarabin was more effective, though more toxic; this combination, in a clinical study, led to 75% of patients responding to treatment, including 20% experiencing complete remission. The treatment response median reached over 66 months. In a small study (10 patients) an increase in the amount of rituximab administrations from 4 to 8 led to a treatment response in 6 patients in whom administration of 4 doses of rituximab had no response. When treating Waldenström macroglobulinemia, effectiveness of the following drugs and their combinations was proven: rituximab, chlorambucil, cyclophosphamide, fludarabin, bortezomib, lenalidomid, bendamustin and alemtuzumab. The same drugs and treatment procedures are used for the treatment of the cold agglutinin disease as for Waldenström macroglobulinemia. Successful treatment with vortezomibem, combinations of rituximab + bendamustin, rituximab + cyclophosphamide or rituximab + fludarabin + cyclophosphamide, were recorded in the form of a description as regards the cold agglutinin disease treatment. An important benefit is also shown through treatment with the monoclonal antibody antiC5, eculizumab, which is otherwise used for the treatment of paroxysmal nocturnal haemoglobinuria. Eculizumab blocks the C5 element of the component and thus stops haemolysis in a patient with cold agglutinin disease. As cold agglutinin disease is very rare, there are only a few clinical studies and when treating this rare disease we have no other option than to take into account the information contained in the descriptions of the particular cases of cold agglutinin disease and the experience of Waldenström macroglobulinemia disease treatment. The discussion seeks to solve the issue regarding what 3rd line treatment option to use in the described patient. Key words: cold agglutinin disease - autoimmune haemolytic anaemia - Waldenström macroglobulinemia - rituximab - fludarabin - bortezomib - bendamustin - cyclophosphamide - eculizumab.
    Vnitr̆ní lékar̆ství 09/2013; 59(9):828-840.
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