Treatment of Nodal Non Hodgkin Lymphoma in West Africa : Experience of Institut Curie in Dakar

In Senegal, few studies have been devoted to non-Hodgkin’s lymphoma. We conducted a retrospective descriptive study of 73 cases treated at the Institut J. Curie Hospital Aristide Le Dantec for non-Hodgkin’s lymphomas from 2001 to 2007. The main objective was to determine the clinical and therapeutic aspects. Our population consisted of 39 men and 34 women (sex ratio: 1.14). The average age was 36 years with extremes of 5 and 76 years. The most common locations were cervical (30.6%) and oropharynx (8.21%). Multiple locations were found in 30.6% of cases. Only 54.4% have histological exam. Patients were managed on cytology basis 42.6% of cases. Histology was performed in 39 patients (54.4%). Among these patients, 69% had aggressive lymphoma, of which 12.82% had a large B-cell lymphoma among indolent lymphomas (59%). The small cleaved cell lymphoma was most often found with 78.26% of cases. The patients were staged with insufficient tools. The protocol most often used was CHOP (64.3%). The most common complications reported were gastrointestinal (11%) followed by skin complications (8.2%). Radiotherapy was performed for 6 patients or 8.2% of cases. Therapeutic strategy was most often used as chemotherapy alone (69.9%). The median duration of follow-up is 18 months.


Introduction
Non-Hodgkin lymphoma (NHL) is among the mature lymphoproliferative disorders.Their incidence is estima-ted at 12.4 cases per 100,000 inhabitants in the United States [1].In the Gambia (West Africa), from 1988 to 1997, they were the second most common cancer [2].
Several studies have investigated the epidemiology, clinics, and therapeutic features of NHL in the Western countries.By cons, few studies have been devoted to this disease in sub-Saharan Africa.The aim of our work is to specify, in a retrospective descriptive study, the clinical and therapeutic characteristics of Nodal NHL treated at the Curie Institute in Dakar.

Institution
Our study is done at Curie Institute of Dakar.This is a referral service providing care for patients with cancer diseases with an annual enrollment of approximately 3000 patients.
This property includes: a radiotherapy unit with a Cobalt 60 machine Alcyon-en chemotherapy day 14 placesa hospital unit of 17 beds.
The staff is composed of clinicians, radiotherapists, chemotherapists and nurses trained in chemotherapy.

Methods
This is a descriptive retrospective study of the records of patients treated for nodal NHL between January 2001 and December 2007.We selected all patients whose diagnosis was based on histology and/or cytology.Exclusive extranodal localizations were excluded.We noted the epidemiological, clinical, paraclinical and therapeutic.
The response was classified into 4 types: complete, partial and progression.Complications were graded according to the WHO grading.

Results
From January 2001 to December 2007, 95 patients were treated for NHL.Our recruitment is 73/95 cases, an average of 9.12 cases per year.The average age was 36 years, with extremes of 5 and 76 years.Age ranges 16 -25, 26 -35 and 46 -55 were the most representative.Our series consisted of 39 men (53.4%) and 34 women (46.6%), giving a sex ratio of 1.14.No patient presented in its history a specific or non specific infectious adenitis.
The locations were most often found cervical multiple, tonsillar and groin.Staging has been clarified that in 40 patients (54.8%).Cytology was performed in 31 patients (42.6%): 29 suspects and two non suspicious.Histological confirmation was made by lymph node biopsy in 39 patients (54.4%).Cytology was performed in 31 patients (42.6%): 29 suspects and two non suspicious.Aggressive NHL accounted for 20.5% of cases, most frequently found were large B-cell lymphomas with 5 cases.Indolent lymphomas accounted for 79.5% of cases with 18 small cleaved cell NHL.
Myelogram was done only for 31 patients (42.6%).Based on the incompletestagingtools, we've noted on the patients record: 17.8% classified as stage I, 9.6% stage II, 11% stage III and 17.8% in stage IV.
Many patients were lost after diagnosis.Chemotherapy was performed in 51 patients (69.86%): 6 to 8 cycles of CHOP regimens.The response to chemotherapy was assessed in 31 cases (42.47%).It was complete in 14 cases.Mean duration of response is 12 months.
Complications of chemotherapy have been reported in 11 patients (15%) of cases: grade 1 and 2 gastrointestinal with 8 cases (11%) and skin type of alopecia in 6 cases (8.2%).Other complications (hematology, pain, weakness, blindness and deafness) are rarer.We noted no complication of grade 3 or 4.
In our series, 6 patients received radiotherapy at a dose of 40 Gy, or 8.2% of cases.She was adjuvant in 3 cases (4.10%) and neoadjuvant in 3 others (4.10%).
Nineteen patients were regularly seen for follow up (26%).In this group, 16 patients had active disease, or 81.21%.A number of 54 patients were lost to 82.2%.
Time monitoring in patients lost to follow ranged from 0 to 60 months, with an average of 8 months.

Discussion
Our work are first to assess the management of nodal NHL in Senegal.The frequency of nodal NHL at Curie institute in Dakar is 9/1000 cases.We find a male predominance with a sex ratio of 1.5 similar to what is reported in the literature [3].
The hypothesis that HIV would be an important causative factor in Africa was mentioned by several studies [4].No patient had HIV infection in our serie.
Superficial lymphadenopathy was the main finding of fact.These results are similar to those found by Tarik in Tunisia [5].Based on the classification of Ann Arbor, we have 17.8% stage IV.In North Africa, the rate is 44.7% [5].
In our study, no patient had a complete diagnostic assessment.Therefore, our therapeutic focus is primarily on a review of the literature.
For proper treatment of NHL, the clinician should apply a few principles: a complete histological and topographic diagnosis including clinical stage, histology with dosing of CD 20, grade and sub grade, the thoracic, abdominal and pelvic CT scan have a good knowledge of toxicity and complications of treatment [6] [7].
After treatment, some patients may unsustainable residual tumor masses containing only wrongly as having a partial remission fibrous tissue.The use of PET-SCAN allows the correct diagnosis [8].
Treatment of early stages was limited for a long time to local radiotherapy.The doses delivered were significant (45 -50 Gy) but the rate of recurrence-free survival was only 40% [10].
Comparing 8 cycles of chemotherapy alone (CHOP) and 3 cycles of chemotherapy (CHOP) with local radiotherapy (30 to 45 Gy) found a better overall survival for chemotherapy with radiotherapy, with less toxicity [11].
The current recommendations for the treatment of aggressive lymphoma in an early stage (stage I or II localized and limited to 2 sites) is based on a 3-R cycles of CHOP protocol followed by locoregional therapy [12].In situations where high doses of radiation are cons-indicated (significant morbidity, oropharynx...), chemotherapy will be maximized to allow irradiation with more tolerable doses: 6 -8 cycles of CHOP-R without radiotherapy is a valid alternative [13].
For the treatment of stage II diffuse NHL, whose prognosis is similar to that of stage III and IV, the treatment will be more aggressive [14].The South West Oncology Group (SWOG) compared protocols CHOP, m-BACOD, MACOP-B and-Pro MACE Cyta BOM in the treatment of follicular lymphoma at an advanced stage (III or IV) [15].The median survival was statistically comparable.The toxicity of grade 3 and 4 these different protocols were respectively 1%, 5%, 4% and 6%.
Unlike the aggressive lymphomas, indolent lymphomas are difficult to cure, and that the goal of treatment is to achieve a complete cure, the major indication for treatment is essentially palliative [16].
Radiotherapy is the treatment of choice for early-stage indolent lymphomas.However, if against indications or patient refusal, abstention more monitoring is an alternative [17].Adjuvant chemotherapy after radiotherapy does not improve the rate of relapse and survival.Survival rates at 5, 10 and 20 years after relapse was respectively 56%, 35% and 17% [18].
At an early stage, patients treated with radiotherapy have an overall 10-year survival of 60% to 80%, with a relapse-free survival at 10 years between 45% and 60% [19] [20].Indolent NHL is also sensitive to single-agent chemotherapy (chlorambucil, cyclophosphamide) and combination chemotherapy (COP), with complete remission rates between 30% and 66% [21].Combinations of more aggressive chemotherapy were used, but the duration of complete remission remains similar [22].
The use of monoclonal antibodies such as Rituximab MAB anti-CD20 alone or in combination was effective in a number of patients with indolent NHL.
In a meta-analysis of seven randomized trials, Rituximab has contributed to: increase response rates, improveed control, better overall survival [23].Most toxicity is related to the Rituximab infusion.Rare cases of mucocutaneous high grade toxicity, including fatalities have been observed [24].Rituximab in combination with interferon-alpha-2a allows achieved a response rate of 45% complete remissions and 11% in 38 patients with refractory or relapsed NHL [25].Fludarabine and Cladribine are effective as single agents [26] [27].

Conclusions
In Senegal, few studies have been devoted to the NHL ganglion.We are faced with a lack of means.This study focused on the efforts to be made for diagnosis, treatment and follow up of patients.
This was made for advocacy to improve our practice and have a "Lymphomastudy group" in Dakar.