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Blood Res 2023; 58(4):

Published online December 31, 2023

https://doi.org/10.5045/br.2023.2023169

© The Korean Society of Hematology

Clinico-pathological features and treatment outcomes of high-grade B cell lymphoma—a tertiary cancer center experience

Anindya Mukherjee, Sujay Rainchwar, Aakanksha Singh, Rohan Halder, Pritish Chandra Patra, Rayaz Ahmed, Dinesh Bhurani, Narendra Agrawal

Department of Hemato-Oncology & Bone Marrow Transplant, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India

Correspondence to : Narendra Agrawal
Department of Hemato-Oncology & Bone Marrow Transplant, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, Delhi 110085, India
E-mail: Narendra_ag1@rediffmail.com

Received: September 1, 2023; Revised: November 18, 2023; Accepted: November 27, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

TO THE EDITOR: High-grade B-cell lymphoma (HG-BCL), an uncommon condition, displays a blastoid morphology and an aggressive disease course, but lacks the features of Burkitt’s lymphoma or diffuse large B-cell lymphoma [1, 2]. Previously termed “B cell lymphoma having features intermediate between DLBCL and Burkitt’s lymphoma” [3], its rarity has primarily resulted in descriptions of isolated case series.

We conducted a retrospective study on 14 patients diagnosed with HG-BCL who were registered in our department between January 1, 2020 and April 30, 2022. Their clinicopathological variables and outcomes at the end of the follow-up period are outlined in the Results.

Epidemiology

The median age was 55.5 (range, 29–7) yr. Most patients were men (N=10, 71.4%). The common comorbidities were diabetes (N=3, 21.4%) and hypertension (N=2, 14.3%). The median symptom duration before diagnosis was eight (range, 1–20) wk. Seven (50%) patients did not have any B symptoms, whereas weight loss (N=3, 21.4%) and fatigue (N=4, 28.6%) were observed in the remaining seven (50%).

Disease workup

Bone marrow biopsy showed disease involvement in six (42.9%) patients. Central nervous system (CNS) involvement was confirmed in 1 out of 14 (7.1%) by a positive cerebrospinal fluid cytology. Four patients (28.6%) showed involvement of the spleen. Extra nodal site involvement was categorized as 1 site (N=7, 50%), ≥2 sites (N=4, 28.6%), and none (N=3, 21.4%). The median IPI and CNS IPI score was 3. High IPI (score of 4–5) and High CNS IPI (score of 4–6) were observed in three (21.4%) patients each.

The common stages observed were stages IV (N=8, 57.1%) and II (N=3, 21.4%). On IHC, five (35.6%) patients were found to be double-expressors of the markers C-MYC, BCL-2, and BCL-6. On analysis by FISH, C-MYC rearrangement was found in two (15.4%) patients with none having concurrent rearrangement of BCL-2 or BCL-6, as shown in Table 1.

Table 1 Molecular marker profiles of patient cohort.

PatientMIB-1, %IHC-Bcl2IHC-Bcl6FISH-C-mycFISH-Bcl2FISH-Bcl6
185-+-
290++-
390+-+--
490+++--
590-
685+-
790++---
880----
990++
1095--
1190++-
1285+--
1395-+---
1495-+---


Therapy

Nine (64.2%) patients received R-CHOP and five (35.7%) received R-DA-EPOCH as first-line therapy. CNS prophylaxis with intrathecal-methotrexate (IT-MTx) was administered concurrently with the R-DA-EPOCH regimen in all five patients, whereas five out of nine patients treated with R-CHOP received the same. High-dose MTx was administered to the remaining four patients on R-CHOP. Three (21.4%) patients relapsed and received salvage chemotherapy with R-GDP (N=2) and R-DHAP (N=1) regimens.

Treatment outcome

The median follow-up duration was 10.5 (1.13–19.3) mo. Response rates after first-line therapy were: complete response (CR), 71.4% (N=10); partial response (PR), 14.2% (N=2); stable disease (SD), none, and progressive disease (PD), 14.2% (N=2), with overall response rates (ORR) of 85.7%. One patient progressed rapidly on first line and died soon after starting therapy. Of the three (21.4%) patients who relapsed, two (14.2%) died from disease progression. The third death was due to COVID-19 pneumonia (Table 2).

Table 2 Clinical outcomes of patient cohort.

Patient1L [CHOP] no. of cycles1L [EPOCH]
no. of cycles
Outcomes of 1L therapyDeathsCause of deathDisease status at last FU
106CRNoNACR
260PDYesPDNA
310PDYesPDNA
460PRYesPDNA
506CRNoNACR
660PRYesCOVID-19 (unrelated)NA
760CRNoNACR
860CRNoNACR
920CRNoNACR
1060CRNoNACR
1170CRNoNACR
1242CRNoNAPR
1342CRNoNACR
1442CRNoNAPR

Abbreviations: 1L, first line; CR, complete response; FU, follow-up; NA, not applicable; PD, progressive disease; PR, partial response; SD, stable disease.



Survival

The mean progression-free survival (PFS) and overall survival (OS) were 14.86 (median, not reached) and 15.58 (median, not reached) mo, respectively. One-year PFS and OS were both 76.2%.

Adverse effects

Acute cytopenia (during and within 6 wk of treatment completion) observed in eight (57.1%) patients was the most common adverse effect. Maximum grade of toxicity was CTCAE 5 (N=3, 21.4%), whereas most common grade was CTCAE 2 (N=11, 78.5%).

To conclude, reports on HG-BCL data in India are scarce [4, 5]. Our study showed promising overall response and survival rates in patients with HG-BCL, despite most patients being in advanced disease stages. However, due to the small cohort size and short follow-up period, variables affecting the outcomes could not be studied. Multicenter pooling can provide greater insight into HG-BCL in the Indian context.

Authors’ Disclosures of Potential Conflicts of Interest

No potential conflicts of interest relevant to this article were reported.

  1. Chen BJ, Fend F, Campo E, Quintanilla-Martinez L. Aggressive B-cell lymphomas-from morphology to molecular pathogenesis. Ann Lymphoma 2019;3:1-22.
    CrossRef
  2. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375-90.
    Pubmed KoreaMed CrossRef
  3. Perry AM, Crockett D, Dave BJ, et al. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and burkitt lymphoma: study of 39 cases. Br J Haematol 2013;162:40-9.
    Pubmed CrossRef
  4. Moharana L, Dasappa L, Babu S, et al. Comparison between CHOP and DAEPOCH with or without rituximab in adult high grade B cell lymphoma, not otherwise specified; a retrospective study from a tertiary cancer hospital in South India. Indian J Hematol Blood Transfus 2022;38:15-23.
    Pubmed KoreaMed CrossRef
  5. Karunakaran P, Selvarajan G, Kalaiyarasi JP, et al. Therapeutic outcomes in high-grade B-cell lymphoma, NOS: retrospective analysis. South Asian J Cancer 2022;11:68-72.
    Pubmed KoreaMed CrossRef

Article

Letter to the Editor

Blood Res 2023; 58(4): 240-242

Published online December 31, 2023 https://doi.org/10.5045/br.2023.2023169

Copyright © The Korean Society of Hematology.

Clinico-pathological features and treatment outcomes of high-grade B cell lymphoma—a tertiary cancer center experience

Anindya Mukherjee, Sujay Rainchwar, Aakanksha Singh, Rohan Halder, Pritish Chandra Patra, Rayaz Ahmed, Dinesh Bhurani, Narendra Agrawal

Department of Hemato-Oncology & Bone Marrow Transplant, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India

Correspondence to:Narendra Agrawal
Department of Hemato-Oncology & Bone Marrow Transplant, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, Delhi 110085, India
E-mail: Narendra_ag1@rediffmail.com

Received: September 1, 2023; Revised: November 18, 2023; Accepted: November 27, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Body

TO THE EDITOR: High-grade B-cell lymphoma (HG-BCL), an uncommon condition, displays a blastoid morphology and an aggressive disease course, but lacks the features of Burkitt’s lymphoma or diffuse large B-cell lymphoma [1, 2]. Previously termed “B cell lymphoma having features intermediate between DLBCL and Burkitt’s lymphoma” [3], its rarity has primarily resulted in descriptions of isolated case series.

We conducted a retrospective study on 14 patients diagnosed with HG-BCL who were registered in our department between January 1, 2020 and April 30, 2022. Their clinicopathological variables and outcomes at the end of the follow-up period are outlined in the Results.

RESULTS

Epidemiology

The median age was 55.5 (range, 29–7) yr. Most patients were men (N=10, 71.4%). The common comorbidities were diabetes (N=3, 21.4%) and hypertension (N=2, 14.3%). The median symptom duration before diagnosis was eight (range, 1–20) wk. Seven (50%) patients did not have any B symptoms, whereas weight loss (N=3, 21.4%) and fatigue (N=4, 28.6%) were observed in the remaining seven (50%).

Disease workup

Bone marrow biopsy showed disease involvement in six (42.9%) patients. Central nervous system (CNS) involvement was confirmed in 1 out of 14 (7.1%) by a positive cerebrospinal fluid cytology. Four patients (28.6%) showed involvement of the spleen. Extra nodal site involvement was categorized as 1 site (N=7, 50%), ≥2 sites (N=4, 28.6%), and none (N=3, 21.4%). The median IPI and CNS IPI score was 3. High IPI (score of 4–5) and High CNS IPI (score of 4–6) were observed in three (21.4%) patients each.

The common stages observed were stages IV (N=8, 57.1%) and II (N=3, 21.4%). On IHC, five (35.6%) patients were found to be double-expressors of the markers C-MYC, BCL-2, and BCL-6. On analysis by FISH, C-MYC rearrangement was found in two (15.4%) patients with none having concurrent rearrangement of BCL-2 or BCL-6, as shown in Table 1.

Table 1 . Molecular marker profiles of patient cohort..

PatientMIB-1, %IHC-Bcl2IHC-Bcl6FISH-C-mycFISH-Bcl2FISH-Bcl6
185-+-
290++-
390+-+--
490+++--
590-
685+-
790++---
880----
990++
1095--
1190++-
1285+--
1395-+---
1495-+---


Therapy

Nine (64.2%) patients received R-CHOP and five (35.7%) received R-DA-EPOCH as first-line therapy. CNS prophylaxis with intrathecal-methotrexate (IT-MTx) was administered concurrently with the R-DA-EPOCH regimen in all five patients, whereas five out of nine patients treated with R-CHOP received the same. High-dose MTx was administered to the remaining four patients on R-CHOP. Three (21.4%) patients relapsed and received salvage chemotherapy with R-GDP (N=2) and R-DHAP (N=1) regimens.

Treatment outcome

The median follow-up duration was 10.5 (1.13–19.3) mo. Response rates after first-line therapy were: complete response (CR), 71.4% (N=10); partial response (PR), 14.2% (N=2); stable disease (SD), none, and progressive disease (PD), 14.2% (N=2), with overall response rates (ORR) of 85.7%. One patient progressed rapidly on first line and died soon after starting therapy. Of the three (21.4%) patients who relapsed, two (14.2%) died from disease progression. The third death was due to COVID-19 pneumonia (Table 2).

Table 2 . Clinical outcomes of patient cohort..

Patient1L [CHOP] no. of cycles1L [EPOCH]
no. of cycles
Outcomes of 1L therapyDeathsCause of deathDisease status at last FU
106CRNoNACR
260PDYesPDNA
310PDYesPDNA
460PRYesPDNA
506CRNoNACR
660PRYesCOVID-19 (unrelated)NA
760CRNoNACR
860CRNoNACR
920CRNoNACR
1060CRNoNACR
1170CRNoNACR
1242CRNoNAPR
1342CRNoNACR
1442CRNoNAPR

Abbreviations: 1L, first line; CR, complete response; FU, follow-up; NA, not applicable; PD, progressive disease; PR, partial response; SD, stable disease..



Survival

The mean progression-free survival (PFS) and overall survival (OS) were 14.86 (median, not reached) and 15.58 (median, not reached) mo, respectively. One-year PFS and OS were both 76.2%.

Adverse effects

Acute cytopenia (during and within 6 wk of treatment completion) observed in eight (57.1%) patients was the most common adverse effect. Maximum grade of toxicity was CTCAE 5 (N=3, 21.4%), whereas most common grade was CTCAE 2 (N=11, 78.5%).

To conclude, reports on HG-BCL data in India are scarce [4, 5]. Our study showed promising overall response and survival rates in patients with HG-BCL, despite most patients being in advanced disease stages. However, due to the small cohort size and short follow-up period, variables affecting the outcomes could not be studied. Multicenter pooling can provide greater insight into HG-BCL in the Indian context.

Authors’ Disclosures of Potential Conflicts of Interest

No potential conflicts of interest relevant to this article were reported.

Table 1 . Molecular marker profiles of patient cohort..

PatientMIB-1, %IHC-Bcl2IHC-Bcl6FISH-C-mycFISH-Bcl2FISH-Bcl6
185-+-
290++-
390+-+--
490+++--
590-
685+-
790++---
880----
990++
1095--
1190++-
1285+--
1395-+---
1495-+---

Table 2 . Clinical outcomes of patient cohort..

Patient1L [CHOP] no. of cycles1L [EPOCH]
no. of cycles
Outcomes of 1L therapyDeathsCause of deathDisease status at last FU
106CRNoNACR
260PDYesPDNA
310PDYesPDNA
460PRYesPDNA
506CRNoNACR
660PRYesCOVID-19 (unrelated)NA
760CRNoNACR
860CRNoNACR
920CRNoNACR
1060CRNoNACR
1170CRNoNACR
1242CRNoNAPR
1342CRNoNACR
1442CRNoNAPR

Abbreviations: 1L, first line; CR, complete response; FU, follow-up; NA, not applicable; PD, progressive disease; PR, partial response; SD, stable disease..


References

  1. Chen BJ, Fend F, Campo E, Quintanilla-Martinez L. Aggressive B-cell lymphomas-from morphology to molecular pathogenesis. Ann Lymphoma 2019;3:1-22.
    CrossRef
  2. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375-90.
    Pubmed KoreaMed CrossRef
  3. Perry AM, Crockett D, Dave BJ, et al. B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and burkitt lymphoma: study of 39 cases. Br J Haematol 2013;162:40-9.
    Pubmed CrossRef
  4. Moharana L, Dasappa L, Babu S, et al. Comparison between CHOP and DAEPOCH with or without rituximab in adult high grade B cell lymphoma, not otherwise specified; a retrospective study from a tertiary cancer hospital in South India. Indian J Hematol Blood Transfus 2022;38:15-23.
    Pubmed KoreaMed CrossRef
  5. Karunakaran P, Selvarajan G, Kalaiyarasi JP, et al. Therapeutic outcomes in high-grade B-cell lymphoma, NOS: retrospective analysis. South Asian J Cancer 2022;11:68-72.
    Pubmed KoreaMed CrossRef
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