|Year : 2014 | Volume
| Issue : 4 | Page : 209-216
Treatment outcome in Egyptian lymphoma patients, 2-year results, single-center experience
Hoda Gad Allah, Mohamed O ElAzzazi, Amal M Elafifi, Hany M Hegab, Mohamed M Moussa, Nevine N Mostafa, Mostafa K Helmy
Department of Internal Medicine and Hematology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
|Date of Submission||02-Dec-2014|
|Date of Acceptance||03-Dec-2014|
|Date of Web Publication||25-Mar-2015|
Mohamed M Moussa
Department of Internal Medicine and Hematology, Faculty of Medicine, Ain Shams University, 65 El Nozha Street, Cairo, 11341
Source of Support: None, Conflict of Interest: None
Introduction Lymphoma is considered the most common hematologic malignancy in Egypt and accounts for about 8.4% of all new cancer cases annually; however, the treatment outcome needs to be evaluated and compared with those achieved with the standards used worldwide.
Patients and methods A retrospective pilot descriptive study of the outcome of patients with lymphoma treated at the Clinical Hematology and Bone Marrow Transplantation Units in Ain Shams University Hospitals over 2 years (2008 and 2009) was carried out. The study included 74 patients, 31 of whom were diagnosed with Hodgkin's lymphoma (HL) (group I), 10 with indolent non-Hodgkin lymphomas (NHL) (subgroup IIa), and 33 with aggressive NHL (subgroup IIb).
Results In this study, NHL was the most common type, found in 58% of the cases, and was more common in older patients; low-grade lymphoma was more common in women and aggressive lymphoma was more common in men. However, HL was found in 42% of cases and was more common in young males. Hepatitis C virus was the most common associated infection; it was detected in 6% of HL and 38% of NHL patients, who were usually in advanced stage disease (80.64% stage III and IV vs. 19.36% stage I and II in HL and 89.19 vs. 10.81% in NHL patients). IPS Hodgkin lymphoma (HL) and International Prognostic Index (IPI) non Hodgkin lymphoma (NHL) were not predictors for treatment response or subsequent relapse. The best results of chemotherapy were achieved using ABVD with IFRT in patients with HL, FC protocol in low-grade NHL, and CHOP-R in high-grade NHL. An overall higher response rate was found in patients with HL compared with NHL patients. ASCT in relapsed patients at the time of the second complete remission did not lead to a significant improvement in disease-free survival or overall survival.
Conclusion Although auto-SCT in NHL in our unit was not statistically significant, but it yielded a good result compared with the international one.
Keywords: Egypt, lymphoma, treatment outcome
|How to cite this article:|
Allah HG, ElAzzazi MO, Elafifi AM, Hegab HM, Moussa MM, Mostafa NN, Helmy MK. Treatment outcome in Egyptian lymphoma patients, 2-year results, single-center experience. Egypt J Haematol 2014;39:209-16
|How to cite this URL:|
Allah HG, ElAzzazi MO, Elafifi AM, Hegab HM, Moussa MM, Mostafa NN, Helmy MK. Treatment outcome in Egyptian lymphoma patients, 2-year results, single-center experience. Egypt J Haematol [serial online] 2014 [cited 2019 Dec 10];39:209-16. Available from: http://www.ehj.eg.net/text.asp?2014/39/4/209/153957
| Introduction|| |
More than 30 types of lymphoma are recognized, with clinical behavior spanning from remarkably indolent to profoundly aggressive .
In Egypt, lymphoma is considered the fourth most common tumor in adults; it represents, 76.6% non-Hodgkin lymphoma (NHL) and 23.4% Hodgkin lymphoma (HL) .
According to the Middle East Cancer Consortium in Egypt, the NHLs age-standardized incidence rates are (16.3/100 000 person). This very high incidence makes NHLs the third most common cancer in Egyptian men and the second most common cancer in women as reported by the National Cancer Institute (NCI), accounting for 10.9% of all cancers in Egypt diagnosed every year .
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL in Egypt, representing about 49% of all NHL cases presenting to the NCI .
HL comprises about 11% of all lymphomas in western countries and has a unique bimodal (sometimes trimodal) age-incidence shape .
The US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) and the European-based International Agency for Research on Cancer population-based cancer registries have estimated the incidence of HL in the USA and in Europe to be around 2.3-3.1/100 000 men and 1.6-2.3/100 000 women, which highlights that HL is a rare malignancy in the general population .
The treatment for aggressive NHL has evolved over the past decades. For more than 25 years, the CHOP regimen (eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone with a 3-week break) has been the standard of care for aggressive lymphomas. Recent modifications include the addition of the monoclonal anti-CD20 antibody rituximab (R-CHOP-21), leading to improved response rates and outcome in large B-cell lymphoma. Other groups have focused on reducing the number of chemotherapy cycles from eight to six and on shortening the intervals between treatment cycles from 3 to 2 weeks (CHOP-14). The latter regimen is also known as 'dose-dense' therapy .
Hematopoietic stem cell transplantation (HSCT) plays a valuable role in the management of lymphoma and can result in long-term remission in selected cases. HSCT usually is performed with curative intent, but requires judicious use because it is associated with considerable morbidity and mortality, which vary markedly between procedures and clinical situations. However, the indications of HSCT in lymphoma patients who are refractory to conventional chemotherapy are still not clear in many situations .
| Aim of the work|| |
The aim of this study is to evaluate the outcome of different treatment methodologies of lymphoma patients in the Clinical Hematology and Bone Marrow Transplantation Units in Ain-Shams University Hospital in the years 2011 and 2013.
| Patients and methods|| |
This study is a retrospective pilot descriptive study of the outcome of patients with lymphoma treated in Clinical Hematology and Bone Marrow Transplantation Units in Ain Shams University Hospital in the years 2011 and 2013.
The study included 74 patients, 31 of whom were diagnosed with HL (group I), 10 with indolent NHL (subgroup IIa), and 33 with aggressive NHL (subgroup IIb). No patients with very aggressive NHL were included in our study.
Clinical presentation and investigations at diagnosis were determined from all patients.
First-line chemotherapy protocols were administered as follows:
- All HL patients received ABVD as a first-line therapy (doxorubicin, bleomycin, vinblastine, and dacarbazine) .
- The first-line therapy for NHL was CHOP ± rituximab (cyclophosphamide, doxorubicin, vincristine, and prednisone) , or FC ± rituximab (fludarabine, cyclophosphamide) , or COP (cyclophosphamide, vincristine, and prednisone) .
The outcome of patients after the first set of chemotherapy (first three or four cycles) was determined according to standardized response criteria where:
- Complete remission (CR) was defined as complete disappearance of all detectable clinical and radiological evidence of disease. All nodal masses decreased to normal (<1.5 cm in diameter for nodes that were >1.5 cm before therapy). If the nodes were initially between 1 and 1.5 cm, they should have decreased to 1 cm or by more than 75% of the sum of the products of the diameter of the nodes (SPD). The spleen, if previously enlarged on CT, had to be normal, and any focal lesions should have resolved. Similarly, the liver and kidney, if involved previously, should have returned to normal. If the marrow was involved, it should be clear. Marrow biopsy, not imaging, is used for this criterion .
- Complete remission unconfirmed/uncertain (CRu) as CR, but with a residual mass greater than 1.5 cm, which should have regressed by more than 75% from the original size. Individual nodes that were confluent should have decreased by more than 75% of pretherapy SPD .
- Partial response (PR) as more than a 50% decrease in SPD of the six largest nodes or masses. These nodes should be from different areas of the body if possible, including the mediastinum and retro peritoneum. No increase in the size of other nodes, liver, or spleen should have occurred. Any splenic or hepatic lesions should have decreased by 50%. Involvement of other organs is assessable, but not measurable disease .
- Stable disease (SD) as less than PR, but not progressive disease (PD) .
- PD as the appearance of new lesions or an increase of more than 50% in established lesions. Increase of more than 50% in the greatest diameter of any previously identified node that was greater than 1 cm .
The second set of chemotherapy for HL was as follows:
(1) ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) , or DHAP (dexamethasone, cisplatin, cytarabine) , or ICE (ifosfamide, carboplatin, etoposide) .
The second set of chemotherapy for NHL was as follows:
(1) CHOP ± rituximab (cyclophosphamide, doxorubicin, vincristine, and prednisone) , or CHOP ± bleomycin (cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin) , or FC ± rituximab (fludarabine, cyclophosphamide) , or COP (cyclophosphamide, vincristine, and prednisone) , or ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin) , or ICE (ifosfamide, carboplatin, etoposide) .
The patients' outcomes were reassessed again after the second set of chemotherapy according to the same response criteria.
Autologous stem cell transplantation was performed for seven patients who developed relapse after receiving the conditioning protocol of chemotherapy:
- Overall survival (OS) was defined as the interval between the beginning of treatment and either death or the time of the last follow-up .
- Disease-free survival (DFS) was defined as the time from achieving CR or CRu to the time of either the first relapse or death from the disease or its treatment or time of the last follow-up for patients who did not develop relapse .
- Statistical presentation and analysis of our study were carried out using the mean and SE, Student's t-test, c2 -test, and analysis of variance tests using SPSS V17 (IBM, USA).
- All numeric variables were expressed as mean ± SD.
- Survival analysis was carried out using the Kaplan-Meier test and comparison of survival between groups was carried out using the log rank test.
- An unpaired Student's t-test was used to compare between two groups for quantitative data.
| Results|| |
The clinical and laboratory data of the patients included in the study are summarized in [Table 1].
|Table 1: The clinical and laboratory data of the patients included in the study|
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As shown in [Table 2], in group I (N = 31), all the patients received the ABVD protocol as an induction therapy; 11 patients achieved CR (35.48%), five patients achieved CRu (16.13%), 14 patients achieved PR (45.16%), none of the patients had SD, and one patient had PD (3.23%).
In subgroup IIa (N = 10), three patients received induction therapy using the CHOP protocol (30%), three patients received the FC protocol (30%), and four patients received the COP protocol (40%). Two patients achieved CR (20%), no patients achieved CRu, six patients achieved PR (60%), one patient had SD (10%), and one patient had PD (10%).
In subgroup IIb (N = 33), 26 patients received the CHOP protocol (78.79%), five patients received the CHOP-R protocol (15.15%), two patients received the COP protocol (6.06%). Four patients achieved CR (12.12%), four patients achieved CRu (12.12%), 22 patients achieved PR (66.67%), two patients had SD (6.06%), and one patient had PD (3.03%).
Differences in the response achieved after receiving the first set of chemotherapy in different groups were not statistically significant.
For second-line chemotherapy as shown in [Table 3], in patients with HL (N = 31), 29 patients received the ABVD protocol as a second set of chemotherapy (93.55%), one patient received the DHAP protocol (3.23%), and another patient received the ICE protocol (3.23%). Twenty-three patients achieved CR (74.19%), five patients achieved CRu (16.13%), and three patient achieved PR (9.68%); no patient had a SD.
In patients with indolent NHL (N = 10), three patients received the CHOP protocol as a second set of chemotherapy (30%), six patients received the FC protocol (60%), and one patient received the COP protocol (10%). Three patients achieved CR (30%), three patients achieved CRu (30%), and four patients achieved PR (40%); no patient had a SD.
In patients with aggressive NHL (N = 33), 19 patients received the CHOP protocol (57.58%), eight patients received the CHOP-R protocol (24.24%), one patient received the FC protocol (3.03%), two patients received the COP protocol (6.06%), one patient received the CHOP-bleomycin protocol (3.03%), one patient received the ICE protocol (3.03%), and one patient received the ESHAP protocol (3.03%). Sixteen patients achieved CR (48.48%), seven patients achieved CRu (21.21%), eight patients achieved PR (24.24%), and two patients had PD (6.06%).
Comparison of the response after the second set of chemotherapy among all patients of different groups was found to be statistically nonsignificant.
As shown in [Table 4], in group I (N = 31), three patients (9.68%) died during the period of follow-up, in subgroup IIa (N = 10) five patients (50%) died during the period of follow-up, and in subgroup IIb (N = 33) 10 patients (30.30%) died during the period of follow-up.
|Table 4: Incidence of mortality among all patients during the period of follow-up using the χ2-test|
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The incidence of mortality among the patients of subgroup IIa was significantly higher than that of both group I and subgroup IIb.
As shown in [Table 5] and [Figure 1], the mean OS among the patients in group I was 5.51 years; this was significantly higher than that of subgroup IIa (2.42 years) and subgroup IIb (3.70 years).
|Figure 1: Kaplan-Meier curve for overall survival of all patients. NHL, non-Hodgkin lymphoma.|
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|Table 5: Comparison of the overall survival of all patients using the log rank test (Kaplan-Meier product limit)|
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In the survival analysis according to autologous SCT, the mean OS was 4.40 years among the group of patients who underwent BMT and 4.68 years among the group of patients who did not undergo bone marrow transplantation (BMT); this was statistically nonsignificant.
| Discussion|| |
Lymphoma is considered the most common hematologic malignancy in Egypt and accounts for about 8.4% of all new cancer cases annually. In this study, we aimed to evaluate the outcome of different treatment methodologies in lymphoma patients.
In this study, 74 Egyptian lymphoma patients with a mean age of 38.6 years (range 18-77 years) were included, 31 of whom were diagnosed with HL (group I), 10 with indolent NHL (subgroup IIa), and 33 with aggressive NHL (subgroup IIb). We studied the impact of different clinical and laboratory risk factors on the OS and DFS of the patients enrolled. We also compared the different groups in the clinical outcome and occurrence of complications.
Patients with HL represented 42% of all the patients, whereas NHL patients represented 58% of patients.
In terms of the association of HCV infection, the incidence was 6%, among HL patients (group I) and 18.6% among NHL patients (group II) as detected by ELISA. In the study by Keresztes et al.  on HL patients, a slightly higher incidence of associated HCV infection was reported in comparison with our study. A study by Cowgill et al.  on Egyptian NHL patients showed a much higher incidence of associated HCV infection compared with our study. In another study by Arcaini et al.  on Italian patients with low-grade NHL, an almost similar association rate of HCV infection was noted compared with the association rate in our low-grade NHL patients.
The lower incidence of associated HCV infection among HL patients compared with NHL was not statistically significant in our study, which is not in agreement with the results reported by De Rosa et al. , who reported a highly significant association of HCV infection in B-NHL patients compared with HL.
Although HIV infection is a recognized risk factor for lymphoma, none of our patients were HIV positive.
The mean total leucocytic count (TLC) at presentation was significantly lower in HL patients compared with low-grade and high-grade NHL patients. In a study by Gobbi et al. , a higher mean TLC for HL patients was noted. The higher mean TLC in that study compared with ours may be attributed to the inclusion of only advanced-stage patients in that study. As an independent predictive factor for response, WBC of at least 15 000/mm 3 was not studied in our study. Its correlation with the DFS and OS was studied by Evens et al. , and showed no statistical significance.
The mean serum LDH level at presentation exceeded the normal range in all groups. A study by El-Sayed et al.  on Egyptian B-NHL patients showed a lower mean LDH level compared with our study.
Another study by Abdelhamid et al.  showed an elevated LDH level in 71% of patients of DLBCL whereas a normal level was found in 29%; serum LDH level had a significant influence on the CR rates in that study. Compared with our study, a lower percentage of patients with aggressive NHL had an LDH level above the normal level; this may be attributed to the smaller sample size in our study. The influence of elevated LDH as an independent risk factor on the outcome was not studied in our study.
In terms of the clinical stage of the disease at presentation:
- In HL (group I), the majority of our patients presented with advanced-stage disease (stage III, IV). The percentage of presentation with advanced stage disease exceeded that reported by Koumarianou et al. . Moreover, in another study by Evens et al. , patients with advanced stage disease represented 64% of all the patients compared with 81% in our study.
- In low-grade NHL patients (subgroup IIa), all the patients presented with advanced stage disease and none presented in stages I or II. Similar results were reported by Federico et al. .
- In aggressive NHL patients (subgroup IIb), the majority of our patients presented with advanced stage disease (stage III, IV). In a study by Abdelhamid et al.  on patients with DLBCL (as an example for aggressive NHLs), a lower percentage of presentation at an advanced stage was reported in comparison with our study. In another study by Portlock et al. , presentation in advanced stage disease was more prevalent as in our study as 68.9% of patients presented with stage III and stage IV.
Consequently, our study showed that there was a significantly high incidence of presentation at an advanced stage disease among all groups of our patients; this may be attributed to delayed presentation of the patients to the healthcare givers (perhaps because of decreased medical orientation).
In terms of the incidence of B symptoms among our patients at presentation, in the HL group, 61.29% of patients were positive for B symptoms, whereas 38.71% were negative. These results were in agreement with the results reported by Gobbi et al.  on advanced stage HL patients.
In the NHL group (group II), 44.18% of patients were positive for B symptoms, whereas 55.82% were negative. Similar results were obtained in the study by Ladetto et al.  on high-risk follicular lymphoma patients. The study by Abdelhamid et al.  on DLBCL showed that a lower percentage of patients were positive for B symptoms compared with our results. Both studies were carried out on a larger number of patients compared with our study; perhaps this had an influence on the results.
The final assessment after chemotherapy showed that 73.03% of the patients were good responders (53.8% achieved CR, and 19.23% achieved CRu) whereas 26.9% had PR. In a study by Coiffier et al.  on elderly DLBCL patients who received CHOP as a first-line therapy, remission rates similar to our study were observed; 63% of the patients achieved either CR or CRu, whereas 22% had PD. Patients who received CHOP-R in the same study responded better (76% achieved either CR or CRu), and the DFS and 2-year survival rate were also better in the CHOP-R group in that study.
In our study, responses were also better for the patients who received CHOP-R as a first-line protocol (five patients); 20% achieved CR, 20% achieved CRu, and 60% achieved PR after receiving three cycles of therapy. At the final assessment of these patients after receiving six cycles of CHOP-R, 40% had achieved CR, 40% had achieved CRu, and 20% (one patient) developed PD.
Responses to COP were inferior to both CHOP and CHOP-R as the two patients who received COP as a first-line protocol achieved PR after three cycles, with no better response after the completion of six cycles in one of them and disease progression in the other.
Comparison of the final responses to chemotherapy ± radiotherapy betweenHL (group I) and NHL (group II) showed that the CR rate was 74.19% in group I compared with 44.19% in group II. The CRu rate was 16.13% in group I compared with 23.26% in group II. The PR rate was 9.68% in group I compared with 27.91% in group II. No PD was present in group I compared with 4.65% in group II. Consequently, there was a significantly higher incidence of a complete response and a lower incidence of progression of the disease in group I compared with group II. This is in agreement with the results reported by other researchers ,,,.
The overall mortality rate was 24.3%; the mortality rate in subgroup IIa was significantly higher than that in the other two groups. 72.2% of the mortalities were disease related, whereas 27.8% were not. 83.5% of the mortalities occurred within the first year from diagnosis. 5.5% of the mortalities were transplant related (TRM). The significantly higher mortality rate in the NHL group compared with the HL group is in agreement with the previously published data by Howlader et al.  in the SEER statistics review for the period (2003-2009).
Seven patients who developed relapse (four with HL and three with aggressive NHL) underwent BMT in their second remission. One patient died of a transplant-related cause. The 2-year survival rate for the patients who underwent BMT was 85.7% compared with 76% in the patients who did not undergo BMT.
The 5-year survival rate in the patients who did not undergo BMT decreased to 73%, whereas that of those who underwent BMT remained constant at 85.7%; this difference was not statistically significant in our study. These results are not in agreement with the previous results reported by Schouten et al.  and Gyan et al.  that the OS is almost similar in treatment-naive lymphoma patients who received high-dose therapy plus ASCT or chemotherapy alone.
The mean DFS did not show a significant difference between the groups who underwent BMT and the group who did not undergo BMT. This is not in agreement with the results published by Gyan et al. , who reported that high-dose therapy plus ASCT significantly improves DFS in comparison with chemotherapy alone.
A small number of patients who underwent BMT were included in our study; this may explain the difference between these results.
Neither the IPS nor the IPI was an accurate estimator of the response, relapse, or mortality rates in our HL and NHL patients, respectively. This is not in agreement with the previous data reported by other researchers ,,; the small number of patients enrolled in our study in comparison with these studies could be an explanation for this result.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]