Splenic re-irradiation for waldenstrőm’s macroglobulinemia
© Zhou et al.; licensee BioMed Central Ltd 2012
Received: 27 December 2011
Accepted: 12 April 2012
Published: 12 April 2012
We report on a case of Waldenström’s macroglobulinemia (WM) treated with splenic re-irradiation. To the best of our knowledge this has not been reported before. A 69-year-old Asian female patient with WM received a three-dimensional conformal radiotherapy, with 24 Gy in 12 treatment fractions in the first stage. She tolerated the treatment well, with a 37% reduction of the monoclonal immunoglobulin, an impalpable spleen, and improved hematological laboratory tests for 4 months. She was then treated with splenic re-irradiation up to 24 Gy for tumor progression. She showed no evidence of progression one year after re-irradiation, with a 55% reduction of the monoclonal immunoglobulin. Our experience demonstrates that splenic irradiation is an effective treatment to control the progression of WM.
KeywordsWaldenström’s macroglobulinemia Lymphoma Radiotherapy
Waldenström’s macroglobulinemia (WM) is a lymphoplasmacytic lymphoma, characteristic of monoclonal immunoglobulin M (IgM) production and bone marrow infiltration . Unfortunately, median survival ranges between 60 and 120 months . Most are symptomatic, such as anemia, leukopenia, splenomegaly, or hepatomegalanemia, and therefore require further treatment to control symptoms . Splenic irradiation (SI) can palliate the pain associated with hypersplenism. Localized radiation of the spleen has been most widely accepted in the management of lymphoproliferative and myeloproliferative disorders [4, 5]. However, relatively little has been discussed on the use of SI in the treatment of WM. We report on a case of splenic re-irradiation for treatment of WM progression. To the best of our knowledge this has not been reported before.
The patient was then referred to SI in December 2009. At that time, palpable splenomegaly increases to 5 cm inferior to costal margin (Figure 1C). A three-dimensional conformal radiation therapy (3D-CRT) plan was designed. In the first stage, the dose prescribed was 24 Gy in 12 treatment fractions via a Varian 23EX linear accelerator. Three oblique isocentric photon fields (4°, 103° and 179°) of beam quality 10-MV were delivered. Mean dose to left kidney, right kidney were 617 cGy and 264 cGy, respectively. Maximum dose to spinal cord was 716 cGy. The patient had been completely asymptomatic with impalpable spleen, and normal hematological laboratory tests for 4 months. In February 2010, she showed a 37% reduction of the monoclonal immunoglobulin.
Discussion and Recommendations
In hematological disorders, splenomegaly is often involved with anemia, leukopenia, as well as thrombocytopenia, which increase the risks of splenectomy. At this time, SI is deemed to be another effective treatment of hypersplenism. However, the effects of SI are usually transient. In chronic lymphocytic leukemia, massive splenomegaly is proved to be related to a shorter therapy-free as well as overall survival . WM progressed in our patient after four months’ completely asymptomatic. The mean duration of remission after palliative spleen irradiation reported in most of the studies was 3 to 6 months, although some cases showed sustained periods of responses . Takemori et al.  and Cavanna et al.  reported two cases of WM treated with chemotherapy and SI resulting in a transient remission, while splenectomy achieving a sustained remission for 6 years and 18 years, respectively.
Here, our patient refused to take chemotherapy or splenectomy, so she was treated with splenic re-irradiation for WM progression. She tolerated the treatment of 3D-CRT up to 24 Gy well. With overall doses between 4 and 10 Gy in mostly 1-Gy fractions, symptoms of splenomegaly have been improved in 50–87% of chronic lymphatic leukaemias patients . Although lower dose per fraction and lower total dose radiation have been a standard in the treatment of hematological and myeloproliferative-associated splenomegaly, we advocate higher doses for sustained remission used to patients with WM, especially those who cannot tolerate operation and chemotharapy. SI may remain practicable for the elderly patients, even with total dose of 20 Gy . Re-irradiation for further symptomatic progression is also carried out in other diseases. It was regarded that splenic re-irradiation was feasible without excessive toxicity. We think that our patient can tolerate re-irradiation up to 24 Gy well, partly because of the use of 3D-CRT. The common technique of SI is two parallel opposing anterior-posterior portals encompassing the whole spleen. The use of 3D-CRT is especially beneficial for patients treated with re-irradiation or patients with impaired renal function.
Here, SI reduced spleen size, myelosuppression, as well as high serum IgM level. Based on previous studies on spleen function, we propose that several biological mechanisms are involved in this effect. Firstly, a direct radiation causes the death of circulating lymphoplasmacytoid cells in the spleen. The main radiobiological mechanism of radiation-induced death is mitotic catastrophe, interphase death and terminal growth arrest (senescence) . Secondly, given that the spleen contained abundant IgM-producing lymphocytes, SI impairs the production of monoclonal immunoglobulin. Peripheral blood mononuclear cells are unable to differentiate into immunoglobulin-secreting cells in splenectomized patients . Thirdly, local radiation induces the spleen release of several cytokines, such as TNF-α, INF-γ and IL-2. These cytokines produce an abscopal effect with immunological responses against distant tumor cells . At the same time, SI impairs normal CD8+ T-suppressor cells function . The absence of CD8+ T-suppressor cells enhances anti-tumour response. Fourthly, high dose of radiation may induce spleen fibrosis, which may prevent from recurrent splenomegaly .
Our experience demonstrates that SI is not only a palliative treatment to relieve the pain of splenomegaly, but also an effective treatment to control the progression of WM. In cases of patients who refuse to have a splenectomy for recurrent hypersplenism, splenic re-irradiation may be another treatment. We recommend the use of 3D-CRT in re-irradiation for better renal protection.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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