Plasmacytoma High-Dose Melphalan Followed by Radical Radiotherapy for the Treatment of Massive Plasmacytoma of the Chest Wall

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Plasmacytoma High-dose melphalan followed by radical radiotherapy for the treatment of massive plasmacytoma of the chest wall

EP Das-Gupta1, GM Sidra1, EM Bessell2, RJ Lush1, JL Byrne1 and NH Russell1

1Department of Haematology, Nottingham City Hospital, Nottingham, UK; and 2Department of Clinical Oncology, Nottingham City Hospital, Nottingham, UK

Summary: affecting his right upper chest in June 1994. A CT scan of his chest revealed two very large soft tissue masses We report three cases of massive chest wall plasma- involving the right chest wall and extending into the lung; cytoma, each greater than 10 cm in diameter, without the larger of the two was 11 cm in diameter. Within the evidence of overt myeloma, whom we treated with a mass, the ribs were abnormal and destroyed. The medial combination of VAD chemotherapy consolidated by high- border of the mass extended to lie adjacent to the right side dose melphalan and autologous peripheral blood stem cell of the upper thoracic vertebrae. CT guided biopsy of the transplantation and radical radiotherapy. All three patients mass demonstrated that this was a plasmacytoma. A 62- completed all components of their therapy without expe- year-old man (patient 2) presented in April 1997 with riencing any major side effects and one patient has had a weight loss and recurrent chest infections. Physical durable remission. The other two patients have had disease examination revealed a palpable swelling with dilated veins progression but at sites other than the original tumour. on his right chest wall. A chest X-ray demonstrated Bone Marrow Transplantation (2003) 32, 759–761. expansion and destruction of the right 7th and 8th ribs doi:10.1038/sj.bmt.1704221 associated with a moderate pleural effusion, and a CT scan Keywords: plasmacytoma; stem cell transplantation; confirmed a mass measuring 13.5 Â 10 Â 15 cm (Figure 1) melphalan; myeloma; high dose therapy arising from the right lower chest wall. Biopsy showed this to be a plasmacytoma with k light chain restriction. The final patient (patient 3), a 51-year-old man, presented with Chest wall plasmacytomas are not unusual in multiple chest pain in February 1998 and was found to have a large myeloma, reflecting the ease with which extraosseous exten- tumour measuring 12 Â 9 Â 7 cm involving his right 3rd rib. sion occurs with rib deposits. Occasionally these masses Biopsy showed a plasmacytoma. The laboratory features of become very large with no evidence of disseminated disease each of these patients at diagnosis are given in Table 1. elsewhere. It has previously been noted that those patients Only patient 3had an excess of plasma cells (7%) in the whose tumour measured 5 cm or more in diameter at bone marrow. diagnosis had a higher risk of treatment failure when managed The plan for all three patients was to debulk the tumour 2 with local radiotherapy alone.1 Although plasmacytomas are with VAD chemotherapy followed by high-dose melphalan generally responsive to VAD-based treatment2 followed by supported by PBSC and to treat the residual mass with radical radiotherapy (35–40 Gy in 20 fractions over 4 weeks), radical radiotherapy as the final treatment (Table 2). One of larger tumours of greater than 10 cm diameter are difficult to the objectives of the initial chemotherapy and high-dose control with this approach. We describe three patients whom therapy was to reduce the field size for radiotherapy and we treated with a combination of VAD chemotherapy thus minimise toxicity to normal lung tissue. In patient 3, consolidated by high-dose melphalan and autologous peri- the treatment plan was modified due to a poor response to pheral blood stem cell transplantation (PBSCT) and radical VAD and the radiotherapy was given prior to the high-dose radiotherapy, one of whom had a durable remission. melphalan for symptom control. Following their VAD chemotherapy, patients underwent stem cell mobilisation using cyclophosphamide 3g/m 2 followed by autologous 2 Patients and methods PBSCT using melphalan 200 mg/m as conditioning chemotherapy. All patients completed the components of the A 50-year-old man (patient 1) presented with a 2-week treatment plan without any major side effects. history of right shoulder discomfort and paraesthesiae

Results

Correspondence: Dr EP Das-Gupta, Academic Haematology, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road, Notting- Currently, patient 2 remains well with normal blood ham NG5 1PB, UK. E-mail: [email protected] counts, calcium and renal function and no detectable Received 14 July 2002; accepted 24 April 2003 paraprotein at 5 years following completion of therapy. HDT of massive plasmacytomas EP Das-Gupta et al 760 He has shown no evidence of local disease recurrence with cervical lymphadenopathy, and biopsy indicated the although he has a residual calciﬁed mass measuring development of an immunoblastic high-grade lymphoma 10 Â 6 Â 13cm. Patient 1 was assessed to be in complete composed of sheets of plasmacytoid cells again showing remission post transplant with no residual mass on CT scan l light chain restriction. He was treated with further and no detectable paraprotein by immunoﬁxation. How- chemotherapy followed by a second autologous stem cell ever, in July 1995, 8 months post transplant, he presented transplant using stem cells harvested in 1994, but he rapidly relapsed and died of progressive disease in August 1997. Patient 3suffered recurrent neck and shoulder pains and in April 2002 was found to have new large lytic lesions in C4, C6 and T1 vertebrae, which required surgical stabilisation. His bone marrow biopsy did not show evidence of progression to myeloma and no serum paraprotein was found. He received radiotherapy and further chemotherapy (cyclophosphamide, thalidomide and dexamethasone) and is now maintained on low-dose thalidomide.

Discussion

Published data on prognostic factors associated with poor overall survival or progression to myeloma for patients with solitary plasmacytoma include advanced age, axial lesions, osteopenia, low levels of uninvolved immuno- Figure 1 CT scan demonstrating a plasmacytoma arising from the right globulins, high paraprotein levels and persistence of 8–10 lower chest wall (outlined by arrows) in patient 2. The plasmacytoma paraprotein after radiotherapy. . Relatively few studies involves and destroys a rib and contains thin linear areas of calciﬁcation. have addressed the impact of tumour size on treatment

Table 1 Laboratory and radiographic features at diagnosis

Patient

12 3

Hb (g/dl) 14.4 14.313.2 WBC ( Â 109/l) 7.5 4.94 12.2 Platelets ( Â 109/l) 215 272 326 Creatinine (mmol/l) 112 17398 Calcium (mmol/l) 2.4 2.28 3.36

b2 microglobulin (mg/l) 2.6 5.5 1.4 Serum paraprotein l free light chains 4.2 g/l 22 g/l IgGk None detectable Urinary paraprotein l free light chains 4.4 g/l 0.004 g/l of free k light chains. 1.47 g/l of IgGk None detectable Skeletal survey Negative Negative Negative Plasma cells in bone marrow No excess No excess 7%

Table 2 Summary of treatment regimens

Patient Treatment Response to VAD Radiotherapy

1 Four cycles of VAD2 2/3reduction in tumour size and disappearance 35 Gy in 20 fractions over 4 weeks. Cyclophosphamide 3g/m 2 of the paraprotein. Planned volume to chest wall 10 Melphalan 200 mg/m2 and PBSCT MV X-rays

2 Four cycles of VAD 2 Reduction in paraprotein from 22 to 2 g/l and 40 Gy in 20 fractions over 4 weeks Cyclophosphamide 3g/m 2 reduction in the size of the mass to using anterior and posterior ﬁelds. Melphalan 200 mg/m2 and PBSCT 12 Â 8 Â 14 cm 5 MV X-rays. Hepatic shielding

3Four cycles of VAD 2 No reduction in tumour size Phase I: 30 Gy in 10 fractions over 2 Since no response to initial treatment, Increasing pain weeks. 6 MV X rays. further chemotherapy was administered in Phase II: 30 Gy in 15 fractions over the form of two cycles of IVE3. Peripheral 3weeks. 5 MV X rays. blood stem cells were mobilised from the Anterior and posterior ﬁelds ﬁrst cycle of chemotherapy. Melphalan 200 mg/m2 and PBSCT

Bone Marrow Transplantation HDT of massive plasmacytomas EP Das-Gupta et al 761 outcome for plasmacytoma. Holland et al7 reported that and one of these patients had evidence of dissemination the size of the primary lesion had prognostic significance in with a low-level plasma cell infiltrate at diagnosis. We predicting conversion to multiple myeloma. In this study conclude that this approach is feasible and may result in of 46 cases of solitary plasmacytoma treated with radio- long-term disease control in a proportion of patients. therapy, the median lesion size for those patients in whom disease progression to myeloma occurred was 7 cm, compared to 3.75 cm for those remaining myeloma-free. Furthermore, 9/11 (82%) of those patients with conversion References to myeloma had lesions that were 5 cm or larger, compared to 5/18 patients (28%) who remained myeloma-free.7 In a 1 Tsang RW, Gospodarowicz MK, Pintilie M et al. Solitary second report of 46 patients with solitary plasmacytoma plasmacytoma treated with radiotherapy: impact of tumor size treated with radiotherapy alone, Tsang et al noted that on outcome. Int J Radiat Oncol Biol Phys 2001; 50: 113–120. those patients whose tumour measured 5 cm or more in 2 Barlogie B, Smith L, Alexanian R. Effective management of advanced multiple myeloma refractory to alkylating agents. N diameter at diagnosis had a higher risk of treatment Engl J Med 1984; 310: 1353–1356. 1 failure. In particular, 5/6 patients with tumours of this size 3McQuaker IG, Haynes AP, Stainer C et al. Stem cell treated with p35 Gy experienced failure of local control. mobilization in resistant or relapsed lymphoma: superior yield Four of these, developed multiple myeloma whereas this of progenitor cells following a salvage regimen comprising radiation dose was found to be adequate for smaller ifosphamide, etoposide and epirubicin compared to intermedi- plasmacytomas, with only 1/14 patients experiencing local ate-dose cyclophosphamide. Br J Haematol 1997; 98: 228–233. treatment failure. Radiotherapy is the recommended 4 Bataille R, Sany J. Solitary myeloma: clinical and prognostic primary treatment modality for solitary plasmacytomas. factors of a review of 114 cases. Cancer 1981; 48: 845–851. Some studies have shown no benefit from adjuvant 5 Jackson A, Scarffe JH. Prognostic significance of osteopenia and immunoparesis at presentation in patients with solitary chemotherapy7 although other reports have suggested that myeloma of bone. Eur J Cancer 1990; 26: 363–371. this may prevent progression of solitary plasmacytoma to 6 Leibross R, Ha C, Cox J et al. Clinical course of solitary 8 myeloma following radiotherapy. The published data extramedullary plasmacytoma. Radiother Oncol 1999; 52: relating to the role of high-dose therapy are restricted to 245–249. a few isolated case reports of patients with multiple 7 Holland J, Trenkner DA, Wasserman TH, Fineberg B. plasmacytomas, which do not address the issue of tumour Plasmacytoma. Treatment results and conversion to myeloma. size.9,10 In the light of studies demonstrating that for Cancer 1992; 69: 1513–1517. patients who present with massive plasmacytomas, radio- 8 Avile´ s A, Huerta-Guzman J, Delgado S et al. Improved therapy alone is unlikely to result in local control or cure, outcome in solitary bone plasmacytomata with combined we employed a treatment strategy incorporating the use of therapy. Hematol Oncol 1996; 14: 111–117. initial VAD chemotherapy, usually reserved for the 9 Vianelli N, Tosi P. The irreplaceable image: plasmacytoma with cutaneous and pleural involvement. Haematologica 1999; treatment of multiple myeloma, followed by high-dose 84: 559. chemotherapy and finally radiotherapy to encompass any 10 Fernandez LA, Couban S, Sy R, Miller R. An unusual residual mass. This treatment was well tolerated and presentation of extramedullary plasmacytoma occurring se- produced a durable remission in one patient. The other quentially in the testis, subcutaneous tissue, and heart. Am J two patients relapsed in new sites not previously involved Hematol 2001; 67: 194–196.

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