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Mukherjee, Rainchwar, Singh, Halder, Patra, Ahmed, Bhurani, and Agrawal: Clinico-pathological features and treatment outcomes of high-grade B cell lymphoma—a tertiary cancer center experience
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.

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).

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.

Notes

Authors’ Disclosures of Potential Conflicts of Interest

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

REFERENCES

1. Chen BJ, Fend F, Campo E, Quintanilla-Martinez L. 2019; Aggressive B-cell lymphomas-from morphology to molecular pathogenesis. Ann Lymphoma. 3:1–22. DOI: 10.21037/aol.2018.12.02.
2. Swerdlow SH, Campo E, Pileri SA, et al. 2016; The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 127:2375–90. DOI: 10.1182/blood-2016-01-643569. PMID: 26980727. PMCID: PMC4874220.
3. Perry AM, Crockett D, Dave BJ, et al. 2013; B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and burkitt lymphoma: study of 39 cases. Br J Haematol. 162:40–9. DOI: 10.1111/bjh.12343. PMID: 23600716.
4. Moharana L, Dasappa L, Babu S, et al. 2022; 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. 38:15–23. DOI: 10.1007/s12288-021-01427-8. PMID: 35125708. PMCID: PMC8804013.
5. Karunakaran P, Selvarajan G, Kalaiyarasi JP, et al. 2022; Therapeutic outcomes in high-grade B-cell lymphoma, NOS: retrospective analysis. South Asian J Cancer. 11:68–72. DOI: 10.1055/s-0041-1739365. PMID: 35833044. PMCID: PMC9273314. PMID: 64de450a1bbd433aa5769b7566be1ed5.

Table 1
Molecular marker profiles of patient cohort.
Patient MIB-1, % IHC-Bcl2 IHC-Bcl6 FISH-C-myc FISH-Bcl2 FISH-Bcl6
1 85 - + -
2 90 + + -
3 90 + - + - -
4 90 + + + - -
5 90 -
6 85 + -
7 90 + + - - -
8 80 - - - -
9 90 + +
10 95 - -
11 90 + + -
12 85 + - -
13 95 - + - - -
14 95 - + - - -
Table 2
Clinical outcomes of patient cohort.
Patient 1L [CHOP] no. of cycles 1L [EPOCH]
no. of cycles
Outcomes of 1L therapy Deaths Cause of death Disease status at last FU
1 0 6 CR No NA CR
2 6 0 PD Yes PD NA
3 1 0 PD Yes PD NA
4 6 0 PR Yes PD NA
5 0 6 CR No NA CR
6 6 0 PR Yes COVID-19 (unrelated) NA
7 6 0 CR No NA CR
8 6 0 CR No NA CR
9 2 0 CR No NA CR
10 6 0 CR No NA CR
11 7 0 CR No NA CR
12 4 2 CR No NA PR
13 4 2 CR No NA CR
14 4 2 CR No NA PR

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

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