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Hematological Oncology

Hematol Oncol 2013; 31: 218220

Published online 22 April 2013 in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/hon.2048

Case Report

Successful treatment of non-Hodgkin lymphoma associated

immune thrombocytopenia with involved eld radiotherapy
Tanya Berrang1, Caroline Holloway1, Jason Hart2, Adrian Yee2, Brian Berry3 and Rami Kotb2*
Radiation Therapy Program, BC Cancer Agency Vancouver Island Centre, Victoria, BC, Canada
Department of Systemic Therapy, BC Cancer Agency Vancouver Island Centre, Victoria, BC, Canada
Department of Pathology, BC Cancer Agency Vancouver Island Centre, Victoria, BC, Canada

*Correspondence to: Rami Kotb, Abstract

MD, BC Cancer Agency Vancouver
Island Centre 2411, Lee Ave, Immune thrombocytopenia complicates the course and impacts the outcome of non-Hodgkin
Victoria, BC, Canada V8R6V5. lymphoma (NHL-ITP, non-Hodgkin lymphomaimmune thrombocytopenic purpura). The
E-mail: rami.kotb@bccancer.bc.ca response to corticosteroids and/or intravenous immune globulins is usually short lasting, but
NHL-ITP usually responds to anti-lymphoma chemotherapy. It is not clear if this success is due
to the elimination of the lymphomatous tissue or to the immunosuppressor/immunomodulator
effect of chemotherapy. Myelosuppressive anti-lymphoma chemotherapy carries the risk of severe
thrombocytopenia that may not respond adequately to platelet transfusion support. We report on a
patient with recurrent diffuse large B-cell lymphoma that coincided with immune thrombocytopenia.
Both diseases completely responded to involved eld radiation therapy. This supports the hypothesis
that at least in some cases of NHL-ITP, the lymphomatous clone secretes the anti-platelet antibodies.
Received 27 December 2012 This supports the therapeutic decision making for these patients. Copyright 2013 John Wiley &
Revised 6 February 2013 Sons, Ltd.
Accepted 8 February 2013
Keywords: immune thrombocytopenia; non-Hodgkin lymphoma; radiotherapy

Introduction negative). Six cycles of CHOP-R (cyclophosphamide,

adriamycin, vincristine, prednisone and rituximab) chemotherapy
Immune thrombocytopenia (ITP) is a common problem for induced a complete remission of 13 months. (Figure 1)
patients with lymphoproliferative disorders. ITP complicates A rst cervical lymph node relapse of DLBCL was con-
the disease course of about 1% of patients with non-Hodgkin rmed by ne needle aspiration and ow cytometry.
lymphoma (NHL) (excluding chronic lymphocytic leukaemia) Restaging imaging and bone marrow biopsy conrmed stage
[non-Hodgkin lymphomaimmune thrombocytopenic purpura II-A disease. Six cycles of CEOPR (cyclophosphamide,
(NHL-ITP)]. Corticosteroids and /or intravenous immune glob- etoposide, vincristine, prednisone and rituximab) induced a
ulins are standard rst-line therapy for patients with ITP outside second complete remission of 8 months.
the context of lymphoproliferation; however, they rarely induce At the time of his second relapse, he was still in good
a durable response in NHL-ITP or NHL. NHL-ITP usually general condition, ECOG-1, with rapidly enlarging cervical
responds to anti-NHL chemotherapy, such as cyclophosphamide, lymphadenopathy. PET/CT scan conrmed disease
vinca alkaloids and the monoclonal anti-CD 20 antibody localized to the neck and nasopharynx (stage II-A) with the
rituximab. These agents are also frequently used in steroid- largest lymph node measuring up to 3.2 cm. Fine needle
refractory ITP. It is not clear if the success of such treatment in aspiration and ow cytometry of a cervical lymph node
NHL-ITP is due to its efcacy eliminating the lymphomatous was positive for malignant large B-cell lymphoma. Labora-
tumour or to better immune suppressive / immune modulating tory work-up, including haemoglobin, red blood cell indices,
effect as in other refractory ITP patients. white blood cell, electrolytes, renal function tests, liver
We report on a patient with recurrent diffuse large B-cell function tests, serum protein, albumin and serum protein
lymphoma (DLBCL) that coincided with immune thrombo- electrophoresis were all normal except for a mild thrombocy-
cytopenia. Both diseases completely responded to involved topenia at 93  109/L (previously 200  109/L) and a lactate
eld radiation therapy. dehydrogenase level at the upper limit of normal. Repeated
Case presentation complete blood counts over a few weeks showed a progres-
sive decline in the platelet counts to 51  109/L. The
An 80-year-old man presented with stage II-A DLBCL involving haemoglobin, the red blood cell and the white blood
the nasopharynx and the cervical lymph nodes (bone marrow cell counts remained normal. The blood smear was

Copyright 2013 John Wiley & Sons, Ltd.

Immune thrombocytopenianon-Hodgkin lymphomaradiotherapy 219

1A 1B transfusion support, clinicians may decrease the initial dose

of myelosuppressive chemotherapy or prioritize the use of
drugs commonly used for refractory ITP. This may have a
signicant impact on the lymphoma outcome. The problem
became more evident with second or third line anti-
DLBCL therapies that are more myelosuppressants and
not commonly used for refractory ITP.
As the spleen is a major site of antibody production and
2A 2B of sequestration of platelets, splenic irradiation has been
described as a potential alternative to splenectomy in
selected ITP patients. Such treatment was never reported
in NHL-ITP [11].
Our case report adds an important insight to the patho-
genesis of this disease by showing that direct targeting of
the lymphoma tissue with a local treatment can improve
associated ITP without associated systemic steroid or im-
Figure 1. Preradiotherapy CT scan at level of the nasopharynx munosuppressive chemotherapy. Our data support a previ-
(1A) and upper neck (1B) with arrows indicating disease. Repeat ous report of NHL-ITP with the production of IgM anti-
CT scan 4 months post-radiotherapy at the same levels (2A, 2B)
platelet antibodies by aggressive lymphoma cells [12]
and two other reports of improved NHL-ITP after surgical
unremarkable. The patient had no bleeding manifestations, removal [13] or radical radiotherapy [14] for indolent lym-
fever, sign of infection or change in prescription or nonpre- phoma. All these data support the concept that in some
scription medications. The reticulated platelet count assay cases of NHL-ITP, the anti-platelet antibody is produced
by ow cytometry was increased to 10.7%, suggesting by lymphoma tissue itself.
increased platelet turnover. Bone marrow biopsy was To our knowledge, no other case reported the improve-
normal, with mild hyperplasia of the megakaryocytic lineage. ment of NHL-ITP using involved eld radiotherapy
There was no dysplasia or bone marrow inltration. The alone. This case improves our understanding of NHL-ITP
diagnosis of immune thrombocytopenia was considered. The and may aid in future therapeutic decision making for
patient received involved eld radiotherapy (20 Gray in ve these patients.
fractions) with excellent tumour response and recovery of the
platelet count to above 230 G/L 2 weeks post-radiotherapy. References
Discussion 1. Smedby KE, Hjalgrim H, Askling J, et al. Autoimmune and
chronic inammatory disorders and risk of non-Hodgkin lym-
Non-Hodgkin lymphomaimmune thrombocytopenic pur- phoma by subtype. J Natl Cancer Inst 2006; 98: 5160.
pura complicates the course of about 1% of patients with 2. Jardin F, Levesque H, Tilly H. Auto-immune manifestations in
NHL and may considerably affect the therapeutic decisions Non-Hodgkins lymphoma. Rev Med Interne 2005; 26: 55771.
3. Wohrer S, Troch M, Streubel B, et al. MALT lymphoma in
[16]. The pathogenesis of NHL-ITP is not fully under- patients with autoimmune diseases: a comparative analysis of
stood and may differ from that of ITP in non-NHL popula- characteristics and clinical course. Leukemia 2007; 21: 18128.
tion. Thrombocytopenia can present before, at or after 4. Hauswirth AW, Skrabs C, Schtzinger C, et al. Autoimmune
diagnosis of NHL and is more frequent in men, contrasting thrombocytopenia in non-Hodgkins lymphomas. Haematologica
the female predominance of ITP [4,5]. 2008 Mar; 93(3): 447450.
5. Varoczy L, Gergely L, Zeher M, Szegedi G, Illes A. Malignant
Corticosteroids, with or without intravenous immune lymphoma-associated autoimmune diseases--a descriptive epide-
globulins, are the rst-line treatment for ITP and chronic miological study. Rheumatol Int 2002; 22: 2337.
lymphocytic leukaemia-associated immune cytopenias. 6. Al-Nawakil C, Park S, Chapuis N, et al. Salvage therapy of
However, NHL-ITP usually has a poor and non-sustained autoimmune thrombocytopenic purpura revealing non-Hodgkin
platelet response to these treatments [710]. A durable lymphoma by the thrombopoietin receptor agonist romiplostim.
Br J Haematol 2012; 156: 1457.
platelet response is usually obtained with effective anti- 7. Bachmeyer C, Audouin J, Bouillot JL, et al. Immune thrombocy-
NHL chemotherapy. It is still unclear if this treatment topenic purpura as the presenting feature of gastric MALT lym-
works by eliminating the lymphoma clone or as many of phoma. Am J Gastroenterol 2000; 95: 1599600.
rst-line anti-NHL agents, including cyclophosphamide, 8. Sakalli H, Akcali Z, Kayaselcuk F, Ozyilkan O. MALTOMA
vincristine, and rituximab are also known immunosuppres- presenting with thrombocytopenia. Am J Clin Oncol 2005; 28: 3212.
9. Magagnoli M, Balzarotti M, Castagna L, et al. Idiopathic
sants/immunomodulators used in steroid-refractory ITP. thrombocytopenic purpura and splenic marginal-zone B-cell
Treating NHL-ITP is challenging. Because of the throm- lymphoma: a casual correlation? Leuk Lymphoma 2003; 44:
bocytopenia that may not respond adequately to platelet 163940.

Copyright 2013 John Wiley & Sons, Ltd. Hematol Oncol 2013; 31: 218220
DOI: 10.1002/hon
220 T Berrang et al.

10. Fink K, Al-Mondhiry H. Idiopathic thrombocytopenic purpura in 13. Noda M, Mori N, Nomura K, et al. Regression of idiopathic
lymphoma. Cancer 1976; 37: 19992004. thrombocytopenic purpura after endoscopic mucosal resection
11. Caulier MT, Darloy F, Rose C, et al. Splenic irradiation for chronic of gastric mucosa associated lymphoid tissue lymphoma. Gut
autoimmune thrombocytopenic purpura in patients with contra- 2004; 53: 1698700.
indications to splenectomy. Br J Haematol 1995; 91: 20811. 14. Watanabe T, Kurihara H, Magarisawa S, Shimoda S, Yoshida K,
12. Nobuoka A, Sakamaki S, Kogawa K, et al. A case of malignant Ishiuchi S. Resolution of immune thrombocytopenic purpura
lymphoma producing autoantibody against platelet glycoprotein associated with extranodal B-cell lymphoma of the petroclival
Ib. Int J Hematol 1999; 70: 2006. region after radiotherapy. Surg Neurol Int 2010; 1: 76.

Copyright 2013 John Wiley & Sons, Ltd. Hematol Oncol 2013; 31: 218220
DOI: 10.1002/hon