The burden of the NHL has increased distinctly in the last years in Yemen. In patients with NHL, the addition of rituximab to standard treatment significantly enhanced response to therapy and overall outcomes. Rituximab is currently approved for the treatment of relapsed and refractory indolent lymphomas as single-agent therapy and as initial therapy in combination with standard chemotherapy regimens [12].
NHL is most often diagnosed in an elderly patient that is aged >60 years, but there is an exception for some types of NHL that are diagnosed in an adult patient [13]. Our study showed the mean age of the patient was 48 years, which is similar to the previous study conducted in Aden, Hadramoot governorates [10, 14], and other studies in China and Mexico [1, 15]. This is due to our patients being contained in all subtypes of NHL.
Regarding gender, our study showed no great difference between males and females (57%). This result is consistent with previous studies in Southeastern governorates of Yemen, Saudia Arabia, and Mexico [1, 16-18]. In contrast, studies conducted in Yemen, and among Chinese patients showed that females more than males, [14, 15] this attributed to the male developing disease more likely than females [19].
Regarding pathological characteristics, advanced stages (Ⅲ, Ⅳ) represented the majority of cases; these findings were in agreement with studies reported in Saudia Arabia, Mexico, and France [1, 18, 20, 21]. On other hand, a study in China revealed that most cases were in stages Ⅰ, Ⅱ [15]. This difference may be due to the lack of early screening of disease in our country.
About 30-40% of NHL patients complain of B-symptoms at the time of diagnosis [5]. our finding revealed that two-thirds of patients did not complain of B-symptoms (67%), which is nearly similar to studies conducted in Mexico and Korea that were (65%, 68%) respectively, and higher than reported from Saudia Arabia (52%) [1, 18, 22].
Cervical lesions represent 28% of all cases in the first of other lesion sites, agrees with a study conducted in Hadramoot [14], and different with a study conducted in Aden which revealed the common lesion was in the abdomen [17].
Diffuse large B cell lymphoma was the most frequent subtype of NHL in our study; this result is similar to a study conducted in Hadramoot Yemen, Aseer Saudia Arabia, and a previous study Middle East region [14, 18, 23]. This is due to DLBCL being the most common form of lymphoma that represents about 30% of NHL [24].
Regarding laboratory investigations, our study showed the abnormality of LDH and B2M in most cases, this finding was agreed with a study conducted in Korea [22], and disagreed with the findings of a study conducted in China. [15] In addition, most cases were a normal count of WBC; a similar result was reported in Saudia Arabia [18]. and CD20 was positive in 67% of patients in our study, which is lower than findings from Saudia Arabia 82% [18]. This difference may be due to variances in sample size, and the percentage of B cell lymphoma that contains about 98% of positive CD20. Furthermore, Only 5% of cases had bone marrow infiltration, which is consistent with findings reported in a previous study [22].
The incidence rate of new cases of non-Hodgkin lymphoma was 19.6 /100,000 per year and the death rate was 5.3 /100,000 per year globally, furthermore, the mortality was about fourth of diagnosed cases of NHL [25]. Our study found that the overall fatality rate was 20% and 30% & 10% for CHOP and R-CHOP, respectively, which is close to the global rate. This result is slightly lower than a study conducted in Korea that found the overall fatality rate was 31% and 57%& 14% for each group, and another study in France showed 35% and (41% & 29%) [20, 22].
In this study, the survival outcome of two groups (CHOP& R-CHOP) was estimated in two follow-up periods in 12 months and 4-year, according to previously evaluated cancer survival analysis [26]. Our findings revealed that the overall survival (OS) in 12-month was 63% and 86%, for CHOP and R-CHOP respectively. This was nearly similar to a study conducted in China for the same period 12-month (75%& 93.8%) [27]. In addition, the progression-free period (PFP) in our study was 39% and 66% for CHOP and R-CHOP, respectively, lower than studies conducted in China (52.8%& 81.2%) [27]. This could be due to many causes such as the low quality of medical services in Yemen compared with other countries, decrease patient outcomes that lead to poor regular follow-up, and most patients coming in advanced stages.
The survival rate has been improving since 1997, thanks to treatment advances. From 2009 to 2018, the death rate decreased by 2% annually. The overall 5-year survival rate for people with NHL is 73% [28]. The 4-years survival rate for patients in our study was 10% and 33% for overall survival of CHOP and R-CHOP groups, respectively. This result was much lower than 5-years survival in the United States (73%), a study conducted in Mexico (61.8% & 65%), and in Korea (94.7% &84.7%) [1,28, 29]. on the other hand, the progression-free survival (PFS) was 12% and 27% for CHOP and R-CHOP, respectively. This is also much lower than other studies conducted in Mexico (63.8 and 51.2%), Korea (50.0% vs. 79.0%), and Germany (59% & 79%) [1,22, 30].
Our finding revealed significant overall survival (OS) of two groups and not significant progression-free survival (PFS), this was consistent with the previous study conducted in China and France that found significant overall survival [15, 20]. In contrast, previous studies conducted in Korea found significant progression-free survival and not significant overall survival, and another study conducted in Mexico found no significance for both overall and progression-free survival [1, 22]. This difference may be due to the most patients were in advanced stages.
The prognosis for non-Hodgkin lymphoma (NHL) varies with the histology, the stage of disease at diagnosis, and the response of the disease to therapy. Furthermore, age ≥60 years, elevated lactate dehydrogenase (LDH) level, Stage III or IV disease, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, and two or more extra-nodal sites [13]. In our study, the significant prognostic factors were the age > 60 years, >6 cycles chemotherapy, abnormality of LDH, and married patient with P-value <0.05. This conforms to studies conducted in Korea and China that found age > 60 years were poor prognostic factors [15, 22]. In contrast, many studies conducted in different countries found these factors not significantly associated with protocol treatment [1,20, 29]. The main limitation in our study was the poor documentation for some processes of treatment of patients and the follow-up results. Lack of a computerized system in the treatment center leads to a lack of the outcome of many patients.
In conclusion, the addition of rituximab to CHOP chemotherapy had a statistical difference in overall survival and there is no difference in PFS. Elderly, married patients, more than 6 cycles of chemotherapy received, and abnormality of LDH were the most important prognostic factors. Therefore, providing the oncology center with Rituximab for ongoing use of NHL patients especially those under 60 years, further assessment for hospital-related risk factors that lead to decreased survival are recommended.