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ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 1  |  Page : 93-97

Autologous bone marrow transplantation for diffuse large B-cell lymphoma in Egypt: a two-center experience


1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Hematology and BMT, Nasser Institute, Cairo, Egypt
3 Department of Hematology, Haematolgy and Haemato-Oncology Hospital, Maady Armed Forces Medical Compound, Cairo, Egypt

Date of Submission06-Mar-2019
Date of Decision31-Mar-2019
Date of Acceptance08-Apr-2019
Date of Web Publication27-Mar-2021

Correspondence Address:
Ghada H Akl
Shebien El-Kom, Menoufia Governorate
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_106_19

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  Abstract 


Objective
The aim of this work was to study the outcome of autologous bone marrow transplantation in diffuse large B-cell lymphoma (DLBCL) according to the experience of two centers, Naser Institute and Sheikh Zayed centers.
Background
Treatment for patients with DLBCL is based on the international prognostic index score and age. Autologous stem-cell transplantation (ASCT) is actually recommended in young patients who did not achieve complete remission after first-line chemotherapy.
Patients and methods
This retrospective case series study included the files of 191 patients who were diagnosed as having DLBCL according to the 2008 WHO classification of lymphoma in Naser Institute and Sheikh Zayed hematology units in the period from 2012 to 2018. The patients were classified into two groups. Group I: patients with DLBCL and received chemotherapy only, Group II: patients with DLBCL and received chemotherapy and then high-dose chemotherapy followed by ASCT (HDC).
Results
The data we had shown that there is no significant statistical difference between the studied groups as regards age and sex. The mean age was 40.34 years (±11.620) in patients with DLBCL and received chemotherapy only while in patients with DLBCL and received chemotherapy then HDC/ASCT was 42.66 years (±11.554). The 5-year overall survival in patients with chemotherapy only is not statistically significant compared with patients with chemotherapy and then HDC/ASCT (P = 0.202).
Conclusion
On the basis of our results, we can conclude that the outcome of HDC/ASCT in patients with DLBCL is nearly equal to the outcome of chemotherapy alone.

Keywords: autologous stem-cell transplantation, chemotherapy, conditioning regimen, diffuse large B-cell lymphoma, non-Hodgkin's lymphoma, staging


How to cite this article:
Akl GH, Shoeib SA, Abdelhafez MA, Abdelhamid AE, Ali AS, Abdelmohsen EA. Autologous bone marrow transplantation for diffuse large B-cell lymphoma in Egypt: a two-center experience. Menoufia Med J 2021;34:93-7

How to cite this URL:
Akl GH, Shoeib SA, Abdelhafez MA, Abdelhamid AE, Ali AS, Abdelmohsen EA. Autologous bone marrow transplantation for diffuse large B-cell lymphoma in Egypt: a two-center experience. Menoufia Med J [serial online] 2021 [cited 2021 May 12];34:93-7. Available from: http://www.mmj.eg.net/text.asp?2021/34/1/93/311984




  Introduction Top


Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. At the present time, it represents about 31% of all NHL in Western Countries and 37% of B-cell tumors worldwide [1].

A molecular risk assessment should be performed in all cases to help determine prognosis and direct therapy. This includes both an evaluation of MYC, BCL2, and BCL6 status (by immunohistochemistry or FISH) and an evaluation of cell of origin (by gene expression profiling or immunohistochemistry-based algorithms) [2],[3].

Using this information, an individual case may be subclassified as one of the following: (a) Germinal center B-cell DLBCL – those are identified by the absence of MYC and BCL2 gene rearrangements. (b) Activated B-cell DLBCL or nongene expression profiling. (c) Double-hit DLBCL – those are cases with MYC translocation plus gene rearrangement of BCL2 and BCL6 (or both) have a poor prognosis with standard therapy. (d) Double-expressor DLBCL in which immunohistochemistry identifies coexpression of MYC and BCL2, but gene rearrangements are not present or were not evaluated [4],[5].

The initial treatment of DLBCL is dependent on the extent of disease. For treatment purposes, patients with DLBCL are generally classified as having either limited-stage disease or advanced-stage disease.

Limited-stage disease (usually Ann Arbor stage I or II): this can be contained within one irradiation field. Limited-stage DLBCL is treated primarily with 6–8 cycles of systemic chemotherapy plus rituximab without radiation therapy may be used [1].

Advanced-stage disease (usually Ann Arbor stage III or IV): this cannot be contained within one irradiation field. Advanced-stage DLBCL is treated primarily with systemic chemotherapy plus the recombinant anti-CD20 antibody rituximab [1],[6].

Relapsed or refractory DLBCL is treated with systemic chemoimmunotherapy ('salvage' therapy) with plans to proceed to hematopoietic cell transplantation in chemotherapy-sensitive patients [7].

The aim of this study was to study the outcome of autologous bone marrow transplantation in DLBCL according to the experience of two centers: Naser Institute and Sheikh Zayed Centers.


  Patients and methods Top


This retrospective case series study included the files of 191 patients who were diagnosed as having DLBCL according to the 2008 WHO classification of lymphoma in Naser Institute and Sheikh Zayed Hematology Units in the period from 2012 to 2018. The patients were classified into two groups: Group I included 68 patients with DLBCL and received chemotherapy only and group II included 123 patients with DLBCL and received chemotherapy followed by high-dose chemotherapy followed by autologous stem-cell transplantation (HDC/ASCT). Informed consent from these two centers was taken to use the data in accordance with the local ethics committee and approved from the Ethics Committee of Faculty of Medicine, Menoufia University.

The diagnosis of DLBCL was based on history and clinical examination with special emphasis on lymph nodes and then biopsy specimens according to the REAL classification criteria and the 2008 WHO classification of lymphoma.

The patients were staged at onset according to the Ann Arbor staging system by physical examination, computed tomography of the neck, chest, abdomen, and the pelvis by Toshiba Aquilion 16 CT Scanner (Toshiba, Minato City, Tokyo, Japan) and bone marrow examination (bone marrow biopsy by 'Jamshidi bone marrow trephine needle from Maharashtra company, Mumbai.' The biopsy is examined under light microscope and analyzed by flowcytometry (NovoCyte Benchtop Flow Cytometer; ACEA Biosciences, Agilent technologies, Santa Clara, CA, USA) and PCR (Roche diagnostics-GmbH, Mannheim, Germany).

Performance status was assessed according to PS scale.

Mobilization protocol in all patients who underwent HDC/ASCT was G-CSF 10 μg/kg for 5 days and stem cells were collected from either bone marrow or peripheral blood through daily apheresis sessions (Rosie Ptia Apharesis System. IS Savannah, US) to reach a dose of at least 3.4 × 106 CD 34 cells/kg.

The outcome of HDC/ASCT was assessed with physical examination, computed tomography assessment, and engraftment speed of neutrophils (neutrophils count assessed by complete blood count analyzed by automated hematological analyzer, Sysmex Corporation, Kobe, Japan).

Statistical analysis

The data collected were tabulated and analyzed by SPSS (the statistical package for the social sciences software) statistical package version 22.0 (IBM Corp, Armonk, New York, USA). Quantitative data were expressed as mean ± SD. It was analyzed by applying t test for comparison between two groups of normally distributed variables. For the qualitative data, it was expressed in the form of number and percentage and then it was analyzed by applying χ2 for comparison between two or more normally distributed independent qualitative variables. Odd ratio and 95% confidence interval were calculated to detect the outcome and overall survival (OS) of patients with ASCT. A P value less than 0.05 was considered as statistically significant.


  Results Top


There is no significant statistical difference between the studied groups as regards age and sex. Age range in patients without ASCT was 17–63 years with a mean age of 40.34 years (±11.620) while in patients with ASCT it was 20–74 years with a mean of age 42.66 years (±11.554) [Table 1]. Among the patients 44 (64.7%) were men without ASCT and 79 (64.2%) in patients ASCT. Women were 24 (35.3%) without ASCT and 44 (35.8%) in patients with ASCT. Bone marrow infiltration was 28 (41.2%) in patients without ASCT and 64 (52%) in patients with ASCT [Table 2]. HCV PCR was positive in three (4.4%) in patients without ASCT and positive in 23 (18.7%) in patients with ASCT. There was complete remission (CR) 1 in 12 (17.6%) in patients without ASCT and zero (0%) in patients with ASCT; CR2 45 (66.2%) in patients without ASCT; and 101 (82.1%) in patients with ASCT; CR3 eight (11.8%) in patients without ASCT; and 17 (13.8%) in patients with ASCT and PR three (4.4%) in patients without ASCT and five (4.1%) in patients with ASCT [Table 3]. The overall 5-year survival was 57.1% in patients without ASCT and 78.3% in patients with ASCT [Table 4] and [Figure 1].
Table 1: Demographic data of the studied groups

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Table 2: Bone marrow infiltration in the studied patients

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Table 3: Disease status at the time of diagnosis of the studied patients

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Table 4: The 5-year overall survival of the two studied groups of patients

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Figure 1: This figure describes the 5-year overall survival of groups I and II in the study.

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There was statistical significance of conditioning regimen used in patients with ASCT as OS in patients according to regimen was: BEEAM, 94.7%; BU-Cy 89.5%; CMV 45.2%; GEM-BU-MELPH 0%; and TBI-Cy 0% [Table 5].
Table 5: The 5-year overall survival in patients in group II in relation to the conditioning regimen used before autologous stem-cell transplantation

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According to pathological stage there was: stage I in 12 (17.6%) in patients without ASCT and three (2.4%) in patients with ASCT; stage II 15 (22.1%) in patients without ASCT and 36 (29.3%) in patients with ASCT; stage III 22 (32.4%) in patients without ASCT and 53 (43.1%) in patients with ASCT, and stage IV 19 (27.9%) in patients without ASCT and 31 (25.2%) in patients with ASCT [Table 6].
Table 6: Ann Arbor pathological stage of the studied patients at the time of diagnosis

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There was no statistical significance of the stage of disease before ASCT with 5 years OS being 64.6% in stages I and II and 69.9% in stages III and IV.

There was no statistical significance of engraftment speed of neutrophils in relation to HCV PCR-positive patients who underwent ASCT as it was less than 5 days one (4.3%), 5–15 days 22 (95.7%), and more than 15 days zero (0%).


  Discussion Top


DLBCL is the most common lymphoid malignancy in adults accounting for 31% of all NHL. ASCT is considered one of the most important lines of treatment of those patients. Many factors can affect the outcome of ASCT [7].

As regards the demographic data of the studied groups, our study showed that there is no significant statistical difference between the studied groups as regards age and sex. The overall 5-year survival was 57.1% in patients without ASCT and 78.3% in patients with ASCT which is better than the 5-year OS in SD. The Smith et al [8]. study showed OS 58% in patients with ASCT and 48% in patients without ASCT.

There is no significant statistical difference as regards the degree of the disease with regard to OS as it was in CR2 (68.4%) and in CR3 (75.3%) and that was the same results in Sweetenham et al. [9] study.

There was statistical significance of conditioning regimen used in patients with ASCT as OS in patients according to the regimen was: BEEAM 94.7%, BU-Cy 89.5%, CMV 45.2%, GEM-BU-MELPH 0%, and TBI-Cy 0%, against the results of Kondo [10] who reported that the OS in patients with ASCT according to the conditioning regimen was: BEEAM 58%, BU-Cy 52%, TBI-Cy 47%.

There was no statistical significance of stage of disease before ASCT with 5 years OS being 64.6% in stages I and II and 69.9% in stages III and IV, against the results of Berthet et al. [11] who found a statistical significance in the OS in large B cell lymphoma patients according to the pathological stage of the disease.


  Conclusion Top


On the basis of our results we can conclude that the outcome of HDC/ASCT in patients with DLBCL is nearly equal to the outcome of chemotherapy alone.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Allen T, Razavi GSE, Khoni NS, Basha N. Competitive treatment in diffuse large B-cell lymphoma (DLBCL) and the future SOC for the first line therapy. Arch Cancer Res 2018; 6:5.  Back to cited text no. 1
    
2.
Barrington SF, Mikhaeel NG. PET scans for staging and restaging in diffuse large B-cell and follicular lymphomas. Curr Hematol Malig Rep 2016; 11:185–195.  Back to cited text no. 2
    
3.
Castillo BS, Rodriguez ML, John Chao JH, Zoghi B. Primary cutaneous diffuse large B-cell lymphoma of the upper limb: double hit/double expressor with CNS involvement: from hospice to remission. Case Rep Hematol 2019;2019:3953470.  Back to cited text no. 3
    
4.
Dubois S, Jardin F. Novel molecular classifications of DLBCL. Nat Rev Clin Oncol 2018; 15:474.  Back to cited text no. 4
    
5.
Bonzheim I, Giese S, Deuter C, Süsskin D, Zierhut M, Waizel M, et al. High frequency of MYD88 mutations in vitreoretinal B-cell lymphoma: a valuable tool to improve diagnostic yield of vitreous aspirates. Blood 2015; 215:260.  Back to cited text no. 5
    
6.
Vaidya R, Witzig TE. Prognostic factors for diffuse large B-cell lymphoma in the R (X) CHOP era. Ann Oncol 2014; 25:2124–2133.  Back to cited text no. 6
    
7.
Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA. Diffuse large B-cell lymphoma. Crit Rev Oncol Hematol 2013; 87:146–171.  Back to cited text no. 7
    
8.
Smith SD, Bolwell BJ, Rybicki LA, Kang T, Dean R, Advani A, et al. Comparison of outcomes after auto-SCT for patients with relapsed diffuse large B-cell lymphoma according to previous therapy with rituximab. Bone Marrow Transplant. 2011; 46:262-6.  Back to cited text no. 8
    
9.
Sweetenham JW, Carella AM, Taghipour G, Cunningham D, Marcus R, Della Volpe A, et al. High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin's disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party. J Clin Oncol 1999; 17:3101-9.  Back to cited text no. 9
    
10.
Kondo E. Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma. Journal of Clinical and Experimental Hematopathology: JCEH. 2016 ;56:100-108.  Back to cited text no. 10
    
11.
Berthet L, Cochet A, Kanoun S, Berriolo-Riedinger A, Humbert O, Toubeau M, et al. In newly diagnosed diffuse large B-cell lymphoma, determination of bone marrow involvement with 18F-FDG PET/CT provides better diagnostic performance and prognostic stratification than does biopsy. J Nucl Med 2013; 54:1244-50.  Back to cited text no. 11
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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