All patients referred to our center (Yopougon University Medical Center, Abidjan) with newly diagnosed Hodgkin or non-Hodgkin lymphoma (HL or NHL), or endemic Burkitt lymphoma and aged 5 to 75 years, were eligible to participate in the AMAFRICA study. Recruitment was based on convenience sampling. Eligibility was based on provisional diagnosis of lymphoma as established by local pathologist (quoted as “referral pathologist” in opposition to the “expert”, see below).
In this study, we prospectively collected information relative to gender, age, marital status (living with a partner versus living alone), employment, residency (Abidjan city versus others), income (<100 USD versus > 100 USD per month), and comorbidity (Charlson’s score).
Diagnosis of ML was based either on biopsy specimens or on cytological and immunological analyses in the presence of circulating malignant cells. Immunophenotype analysis of peripheral mononuclear circulating cells were performed in Cerba® Laboratory (a private institution located in Paris, France) and resulted in the characterization of B- or T-derived main subtypes (CD3, CD8, CD4, CD8, CD56, CD19, CD20). Biopsy specimens were processed at the Pathology Department of Treichville University Medical Center in Abidjan. At this level, morphological examination was performed after HE staining without immunohistochemistry (IHC).
However, materials were also addressed in duplicate to the Pathology Department of the Toulouse University Medical Center (France), Prof. Camille Laurent as referent. The reviewing procedure was performed not only with morphology analysis, but also with IHC using a combination of monoclonal antibodies and more occasionally molecular biology according to standardized procedures6. Patients with insufficient materials resulting in uncertainty about ML diagnosis were excluded. According to the centralized histopathological review we used in France for lymphoma diagnosis (the Lymphopath Procedure), discordance between referral and expert referred to any change made by the expert on the basis of the WHO lymphoma classification6.
At diagnosis, routine biological analyses (blood cell count, LDH, hepatic enzymes, CRP) as well as a CT Scan were performed for each patient. Post-treatment routine biological analysis and CT scan were performed only for patients who achieved their therapeutic plan.
The chemotherapy was planned as follows: For HL: ABVD protocol for 6 cycles. For NHL, CHOP protocol 6 cycles or RCHOP (CHOP 6 cycles + Rituximab 375 mg/m2 at each cycle). Rituximab was used for patients with insurance (n = 10). Burkitt lymphomas (BL) were treated with the CMA regimen as described previously by one of us7. Importantly, costs related to transportation, hospitalization and drugs remained payable to patients.
The AMAFRICA procedure:
AMAFRICA started when the NN met the patient for the first time and assisted the oncologist in informing the patient about the objectives of the study and the methods, including the randomization (AMAFRICA versus standard). In case of acceptance, informed consent was collected and biopsy specimens were sent to France for review. Randomization was realized in France, based on provisional diagnosis (before the review). However, only patients with confirmed diagnosis of lymphoma (after review) entered into the study. The expert review was done in a timely fashion, so chemotherapy was administered within a reasonable time limit.
Once included, patients assigned to the AMAFRICA group received free cellular phones to communicate with the NN during treatment.
During therapy, according to the AMA procedure previously described 4 , the NN called the patients weekly and collected all information related to treatment-induced toxicity (notably, fever, respiratory signs, mucositis, pains, digestive troubles). These data were recorded in a clinical report form which was addressed to the oncologist. The NN was trained for a period of one month in France.
The study was started in May 2015 and recruitment ended in November 2017 (n = 100 patients included).
Costs related to transportation, hospitalization and drugs were payable to patients. Pierre Fabre Foundation covered the costs related to the study itself including: Nurse Navigator salary, transportation and analysis of biopsy specimens, CT scan and routine biology for staging and post-treatment evaluation. Pathological review in Toulouse was free, including reagents and working time.
Ethics and Consent to participate
The study was approved by the Ethical Committee of Abidjan University Medical Center (N°027/MSLS/CNER-dkn). The informed consent obtained from study participants was written.
Refusal referred to patients who entered into the study but refused chemotherapy.
Abandonment referred to patients who entered into the study, received at least 1 cycle and then decided to stop therapy.
Non-adherent patients referred to patients who entered into the study, achieved their chemotherapy plans, but received less than 75% of the theoretical total dose for doxorubicin and/or cyclophosphamide.
Adherent patients referred to patients who entered into the study, achieved their chemotherapy plans, and received at least 75% of the theoretical total dose for doxorubicin and cyclophosphamide.
Complete response was based on intent-to-treat and assessed according to Cheson’s criteria 1999 8.
Overall survival was measured from the entry into the study; any cause of death was considered.
Data collections and analysis
SPSS (IBM Corporation, Armonk, NY, USA) was used to conduct data management and analysis. For each variable, frequency distributions, median, means, and standard deviations were calculated. Differences in socio-demographic and clinical characteristics between the two groups were compared using chi-square, Fisher’s exact, and t-tests. Fisher’s exact test for variables with over two categories was executed in R version 2.15.0. Survival analysis was performed using the Kaplan-Meier method. Overall survival was calculated from treatment initiation to death from any cause or at the date of the last visit. For comparison of cohorts, the Mann-Whitney test was employed.