High-dose chemotherapy and is usually not successful. Since 1992, three patients with relapsed primary nasal T/NK cell lymphoma have autologous stem cell ...
Bone Marrow Transplantation, (1997) 19, 91–93 1997 Stockton Press All rights reserved 0268–3369/97 $12.00
Case report Autologous bone marrow transplantation for primary nasal T/NK cell lymphoma R Liang1, F Chen1, CK Lee1, YL Kwong1, CS Chim1, CC Yau2 and E Chiu1 Departments of 1Medicine and 2Radiation Oncology, University of Hong Kong, Queen Mary Hospital, Hong Kong
Summary: Primary nasal T or NK cell lymphoma is rarely seen in the Western population but is more common in the Orientals. Although it often presents with localized disease, the prognosis is generally poor. Long-term remission is seen in only 50% of patients with stage I disease despite aggressive treatment with chemotherapy and radiotherapy, and is invariably fatal if disseminated. Conventional chemotherapy for relapsed disease is usually not successful. Since 1992, three patients with relapsed primary nasal T/NK cell lymphoma have received high-dose chemotherapy with autologous bone marrow rescue at Queen Mary Hospital, Hong Kong. High-dose cyclophosphamide, BCNU and etoposide were used for conditioning. Two of them had a favourable response and remained in complete remission at 12 and 44 months post-transplant. The third patient unfortunately had a systemic relapse 6 months after the transplant. It appears from this experience that, like other aggressive non-Hodgkin’s lymphomas, high-dose chemotherapy and autologous bone marrow rescue is an effective treatment for relapsed primary nasal lymphoma following failure of conventional chemotherapy and radiotherapy. Keywords: nasal lymphoma; autologous bone marrow transplantation
Primary nasal lymphoma is extremely uncommon in the Western population. When it occurs, it often affects the nasal sinuses and is usually of B cell origin. On the other hand, it is much more common in the Orientals.1–4 The reason for the discrepancy remains obscure. Primary nasal lymphoma accounts for at least 5% of all non-Hodgkin’s lymphoma seen in Hong Kong Chinese.2 The tumour tends to affect the mid-line nasal cavity.3 It has the histological features of angiocentric lymphoma which is characterised by prominent angio-invasion by tumour cells.4 The malignant cells often carry T cell and/or NK cell markers but clonal rearrangement of the T cell receptor genes is consistCorrespondence: Professor R Liang, Department of Medicine, Queen Mary Hospital, Hong Kong Received 20 May 1996; accepted 22 August 1996
ently negative.5–7 Furthermore, clonal Epstein–Barr viral infection has been documented in many of these cases.6 Patients with primary nasal lymphoma usually present with local nasal symptoms and the tumour is often clinically localised.3,8 However, the prognosis is generally poor as compared with their nodal counterparts.8 Durable remission is only seen in around 50% of stage I patients and the disease is invariably fatal if disseminated. For patients with relapsed disease, the prognosis is also dismal as they almost all die with progressive disease within 1 year from the time of relapse. High-dose chemotherapy and autologous stem cell rescue has been shown to be an effective therapy for patients with relapsed aggressive nonHodgkin’s lymphoma.9 We report our experience of using the approach to manage three patients with relapsed primary nasal lymphoma. Case report Since 1992, three Chinese patients with relapsed primary nasal T/NK cell lymphoma have received high-dose chemotherapy and autologous bone marrow rescue at the Bone Marrow Transplantation Unit of Queen Mary Hospital, Hong Kong. Their clinical characteristics are shown in Table 1. The conditioning regimen consisted of cyclophosphamide 1.8 g/m2/day for 4 days, BCNU 100 mg/m2/day for 3 days and etoposide 400 mg/m2 12 h for six doses. The first patient was a 30-year-old woman. She presented with a nasal mass and symptoms of nasal obstruction in February 1992. Biopsy of the tumour revealed a primary nasal lymphoma (CD2+, CD56+). Staging investigations confirmed that she had disease localised to the nasal cavity. A complete remission was achieved after three courses of ProMACE-CytaBOM chemotherapy, which consisted of cyclophosphamide 650 mg/m2 IVI day 1, doxorubicin 25 mg/m2 IVI day 1, etoposide 120 mg/m2 IVI day 1, prednisolone 60 mg/m2 orally day 1 to 14, cytosine arabinoside 300 mg/m2 IVI day 8, bleomycin 5 mg/m2 IVI day 8, vincristine 2 mg IVI day 8 and methotrexate 120 mg/m2 IVI day 8 (with folinic acid rescue). Local radiotherapy was planned but the tumour recurred locally before it was given. She was reinduced with local radiotherapy and IMVP-16 chemotherapy consisting of ifosfamide 1 g/m2 days 1 to 5, methotrexate 30 mg/m2 IMI days 3 and 10, and etoposide 100 mg/m2 IVI days 1 to 3. Only a partial remission was
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Table 1
Clinical characteristics 1st patient
2nd patient
3rd patient
Sex
female
female
female
Age (years)
30
34
20
Ann Arbor stage
I
I
I
Histology (Working Formulation)
diffuse large cell
diffuse mixed small and large cell
diffuse mixed small and large cell
Immunophenotype
CD2, CD56+ B markers−
CD2, CD56+ B markers−
CD2, CD56+ B markers−
B symptoms
No
No
No
Bulky tumour
Yes
No
No
Response to initial therapy
Complete remission
Complete remission
Complete remission
Duration of first remission
3 months
16 years
7 months
achieved after three courses of IMVP-16. High-dose chemotherapy with autologous marrow rescue was given in September 1992, which resulted in complete remission. She tolerated the procedure well except for one episode of neutropenic fever that responded to antibiotic therapy. The patient remains well and free of disease 44 months posttransplantation. The second patient was a 34-year-old woman. She presented with nasal bleeding in 1978 and was diagnosed to have a clinically localised primary nasal lymphoma (CD2+, CD56+). A complete remission was achieved with local radiotherapy alone. Unfortunately, the tumour recurred locally in 1994. She was reinduced with CEOP chemotherapy consisting of cyclophosphamide 750 mg/m2 IVI day 1, epirubicin 60 mg/m2 IVI day 1, vincristine 2 mg IVI day 1 and prednisolone 100 mg/m2 orally days 1 to 5 and only a partial remission was achieved after three courses. Residual tumour cells persisted even after a further three courses of IMVP-16 chemotherapy (schedule identical to that for the first patient). High-dose chemotherapy with autologous marrow rescue was given in June 1995, resulting in complete remission. She tolerated the procedure well. The patient remains well and free of disease 12 months post-transplantation. The third patient was a 20-year-old female. She presented with nasal bleeding and symptoms of nasal obstruction in February 1993. Biopsy of the nasal tumour revealed a primary nasal lymphoma (CD2+, CD56+). Staging investigations confirmed that she had disease localised to the nasal cavity. A complete remission was achieved after six courses of m-BACOD chemotherapy consisting of bleomycin 4 mg/m2 IVI day 1, doxorubicin 45 mg/m2 IVI day 1, cyclophosphamide 600 mg IVI day 1, vincristine 2 mg IVI day 1, dexamethasone 6 mg/m2 orally days 1 to 5 and methotrexate 200 mg/m2 IVI days 8 and 15 (with folinic acid rescue). It was further consolidated by local radiotherapy. Unfortunately, the tumour recurred locally in November 1993. A second complete remission was achieved with three courses of IMVP-16 chemotherapy (schedule identical to that for the first and second patient). High-dose chemotherapy with autologous marrow rescue was given in June 1994. She had an episode of neutropenic fever during the procedure that responded to antibiotic therapy. The
tumour unfortunately relapsed 6 months post-transplantation. The patient eventually died of progressive disease.
Discussion Primary nasal T/NK cell lymphoma is often classified as an angiocentric lymphoma which is characterised by angiocentric and angio-destructive lymphoid infiltrates admixed with plasma cells, eosinophils and histiocytes.4 As a result of the angio-invasion, tissue ischaemia and necrosis are usually prominent. Together with its anatomical location, adequate biopsy tissue for diagnosis is often difficult to obtain. The ischaemic nature of the tumour may also partly explain its poor response to chemotherapy and radiotherapy.8 Local tumour recurrence is common following treatment. It has been demonstrated that high-dose chemotherapy with marrow or stem cell rescue is an effective treatment for relapsed non-Hodgkin’s lymphoma. 9,10 Durable longterm remission can be achieved in a significant proportion of these patients and favourable results have been seen in a group of patients with chemo-sensitive disease. We are interested in exploring the effectiveness of this treatment for patients with relapsed primary nasal lymphoma. All three patients with primary nasal lymphoma who had highdose chemotherapy and autologous bone marrow transplant in our hospital had either partial or complete remission following salvage chemotherapy before transplant. Durable complete remission was observed in two of them. It appears from this initial experience that high-dose chemotherapy and autologous bone marrow transplantation is an effective treatment for relapse primary nasal T/NK cell lymphoma following failure of conventional chemotherapy.
Acknowledgement We wish to thank Professor Faith Ho for reviewing the biopsy specimens of the patients.
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