Primitive bone lymphoma: Tunisian multicentre retrospective study about 32 cases.
Summary
Goal: Studying the epidemiological and clinical characteristics, treatment modalities, and prognosis of the primitive bone Lymphoma (LOP) on a Tunisian retrospective series.
Patients and methods: we collected cases of LOP histologically confirmed in three departments of medical oncology of the North and center of the Tunisia and we analyzed their epidemiological characteristics, the treatment protocol and the results.
Results: We have compiled from January 1990 to July 2014, 32 patients whose median age was 53 years. The LOP touched especially the long bones, femurs, tibiae and humerus with a plurifocale breach in case 3/32. It was most of the stages early I and II and in 91% of B Lymphoma large cell. All the patients had chemotherapy (CT) in majority of type CHOP, associated with rituximab for the 9 most recent cases. 14 patients/32 patients received radiotherapy of loco-regional and one patient had a surgical resection of type resection and reconstruction. The clinical-radiological objective responses after TB rate was 90%. With a median follow-up of 38.5 months (months 1-192), the 5-year overall survival (OS) rate was 63%, 14 patients are living in remission and 18 have presented relapses loco-regional or systemic.
Conclusion: The LOP remain rare, even belatedly diagnosed disease in Tunisia. However, the majority of patients are diagnosed in early stages. The progress of the CT, especially since the introduction of Rituximab, allow obtaining a high objective response rate and an improvement in survival.
Key words
Lymphoma, non Hodgkin, primitive, os, classification, stage, chemotherapy, objective response, survival.
Article
Introduction
Primary non Hodgkin lymphomas of bone gold PBL are rare, accounting for less than 1-2% of adult Non Hodgkin Lymphomas (NHL) and less than 7-10% of primary bone tumors (1,2). PBL is defined as a localized lymphoma in year osseous site without evidence of disease elsewhere for at least 6 months. The presence of regional lymph nodes does not exclude the diagnosis of PBL [1]. Treatment is based on chemotherapy (CT), with Rituximab for B-cell lymphomas (AMLD), goal loco-regional radiotherapy (LRT) and more rarely orthopedic reconstructive surgery could be indicated.
We report the results of a retrospective study concerning patients treated in three hospitals in Tunisia, with histologically confirmed PBL during university has 24 years period.
Patients and methods
We collected patients with histologically-confirmed PBL treated over has 24years period at northern and central Tunisia (1990-2014) in Tunis from Salah site Institute, Abderrahman Mami Hospital and in Sousse from Farhat Samantha university hospital. Staging investigations included: physical examination, performance status, laboratory tests (complete blood count, lactate dehydrogenase (LDH) and complete metabolic profile), best abdominal computed tomography (CT scan) and bone marrow biopsy. PBL cases were classified according to Ann Arbor: internship I consisted in single localized bone lesion, stage II consisted in bone lesion with lymph node involvement on the same side of the diaphragm, stage III consisted in bone lesion with remote lymph nodes involvement and internship IV included multiple bone lesions or a single large bone lesion. All patients assigned a score using the Age Adjusted International prognosis Index (IPI) system including 3 of the above factors: internship, LDH and Performance status, the sum of the points allotted correlates with the following risk groups: Low risk (0 points). Low-intermediate risk (1 point), High-intermediate risk (2 points) and High risk at 3 points. We grouped patients by IPI score into group 1 including those with scores 0-2 and group 2 for those with scores > 2. All patients received CT mainly by CHOP (Doxorubicin, Cyclophosphamide, Vincristine and Prednisone) or CHOP-like protocols such as ACVBP (Adriamycin, Cyclophosphamide, Vincristine, Prednisone and Bleomycin) and relapsing patients ICE (Ifosfamide, Carboplatin and Etoposide) and DHAP(Dexamethasone, Cisplatin, high dose Aractyin). Since its availability in 2004, patients with AMLD received Rituximab in addition to CT. Radiotherapy (RT) was prescribed in emergencies at a dose of 30 Gy in 10sessions in case of severe pain and/or spinal cord compression) or in stage I diseaseat doses from 46 to 54 Gy in 15 to 27 sessions. Surgery was performed in situation of pathologic fractures. Response to CT and/or CT was evaluated clinically and radiologically at the end of the protocol.Complete response was defined as total control of bone bread, normal LDH level and disappearance of bones lesions with reconstruction. Partial response was defined as control of bone pain and regression of more than 50% of bone lesions. We analyzed the epidemiological, clinical, histological features, treatment protocols and therapeutic results.
Results
We collected thirty-two (32) patients, with a median age of 53 years (20 to 87 years) and a 1.6 ratio. Bone pain was the major symptom (53% of patients) andmean time to diagnosis was 9 months (2-24 months). PBL predominates in long bones (66%), while axial rental was seen in 13 boxes; being were exclusively osteolytic lesions (Figures 1 and 2). Regional lymph nodes and soft tissue involvement were seen in respectively 10 and 2 boxes. All patients had high grade lymphomas of B-cell lineage in 91% of cases, the 9% being resting T-cell type or anaplastic. Patients were classified according to Ann Arbor classification as stage I, II and IV in respectively 13, 9 and 10 boxes. 68% of patients were staged in group 1 IPI score and 32 %(10 patients) in group 2 IPI score. Patients received CHOP-CT in 28 boxes and ACVBP in 4 cases, associated to Rituximab in 9 boxes. Two patients scored 2 IPI, was intensifying and autologous stem cell after objective responses to ACVBP. Loco-regional RT was used in 14/32 patients, curative in 6 boxes and for bread and spinal cord compression in respectively 5 and 3 squares. One patient complete responder after 6 cycles of ACVBP, had a resection and reconstruction of his femoral PBL due to year initial pathologic fracture. Histologic examination showed a complete histologic response (pCR) in the resected femoral tumor. After primary CT, we observed 80% of clinical and radiological response rate (MRCC) partial and complete in 10 boxes. With a median follow-up of 38.5 months, varying from 1 to 192 months, the 5-year OS was at 63%.3 died by severe sepsis after grade IV-induced neutropenia patients, 14 (43%) presented local relapses in bones, 4 (12%) had remote relapses in testis, lymph nodes orbit and pericardium. Salvage treatment consisted one in CT 6 patients and LRT in 3 boxes. One of our patients who presented a bone relapse treated by CT (RGEPD: Rituximab, Gemcitabine, Etoposide, Prednisone and doxorubicin) is still alive in complete remission and he has two babies. By the time of our study 11 patients remain alive in complete remission.
Discussion We picked up from 3 university hospitals in Tunisia, 32 boxes of PBL, over has 24 years period confirming the rarity of this disease that represents less than 1% of primary bone tumors in literature [1,2]. PBL affects the middle-aged to elderly population, with a slight predominance in men [1,2]. The mean age in our series was 53 years. We compared them to 3 wide series of PBL, from Memorial Sloan-Kettering cancer center [3], British Columbia Cancer Agency [4] and Multicenter Rare Cancer Network [5] that concerned respectively 82, 131 and 116 patients (Table Iand II). We observed for our patients prolonged median delay to at 9 months, PBL diagnosis being rarely suggested initially because symptoms of bone and/or articulate bread aren't specific nor pathognomonic, and general symptoms (fever, night sweats) are rare. Most patients have repeated consultations and treatment by anti-inflammatory and analgesics prescribed by first line physicians and rheumatologists/orthopedics. PBL arises in flat and axial bones, but can be also affected long bones [7.4]. Radiologic lesions are mostly osteolytic, without any specific aspect in imagery [8]. Lesions can be multifocal (4 of our boxes). Histology, based on fine needle biopsy for all our patients concluded to high grade B-cell lymphomas in 29/32 patients, comparable to literature data [4, 5, 7, 9]. PBL is more often diagnosed in early-stage, even when diagnosis is delayed [4: 10].
Additionof Rituximab to chemotherapy was year important progress in the treatment of high grade B-cell NHL. In Tunisia, Rituximab was approved since 2004. All the patients were treated with anthracyclin-based chemotherapy (CHOP or ACVBP), with year objective response rate of 90%, and 10% of complete response. We indicated, have salvagetreatment, intensification for 2-high-risk-IPI patientsand they're still alive in complete remission. Loco-regional RT was used in 14/32 patient for isolated bone lesions in early patient treated and/or in case of emergency or bread. In the literature, the role of radiation therapy is still a matter of debate. Ramadan and al. found that addition of RT to CT deteriorates survival rate [5]. However, Ling Cai and Barbieri, showed that RT was associated with a better 5-year survival in patients with early-stage PBL [6, 11, 12]. A recent publication reported the results of a retrospective study concerning 70 patients with PBL, treated between 1985 and 2013 by CT alone (45/70) Gold combined CT - RT in 24 patients (11). RT concerned bulky disease or incomplete response to CT. Despite no. difference in term of 5 year survival patients that received RT were more likely to experience fracture healing (p = 0.01) and have a higher risk for fracture in the post-treatment period observed in 5/24 pts (p = 0.0375).
Despite the high response rate after primary CT, median time to relapse was shorter than in US and Asian series of PBL [4: 13]. Indeed, in recent studies, most are treated with radiotherapy, chemotherapy and Rituximab combined PBL. Also, the majority of studies reported early staged lymphoma.
Conclusion PBL is a rare disease is the most frequent subtype andDLBCL. It has a fairly good prognosis. The role of CT is central in its treatment and the addition of Rituximab improved outcomes. However, radiotherapy's role is not well established steel. Large prospective studies are needed to develop the appropriate treatment and recommendations.
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