Rituximab-based regimens for primary cardiac lymphoma: A systematic review of outcomes, challenges and future directions

Abstract

BACKGROUND

Primary cardiac lymphoma (PCL) is a rare subset of cardiac tumors, often diagnosed late due to nonspecific symptoms. It predominantly affects immunocompromised individuals, primarily in the pericardium and right heart. Late diagnosis mimics common cardiac ailments, leading to poor prognosis.

AIM

To systematically review the efficacy of rituximab in treating PCL either alone or in various chemotherapeutic regimens. Secondary objectives include evaluating morphological subtypes, assessing treatment regimens, and analyzing outcomes focusing on remission and adverse events.

METHODS

Following PRISMA guidelines, a comprehensive literature search was conducted across multiple databases, including PubMed, Hinari, Web of Science, and Scopus. English-language studies reporting the use of rituximab in treating PCL in humans were included. Study selection involved initial screening of titles and abstracts followed by full-text examination and data extraction.

RESULTS

Thirty-three case reports involving 36 patients were included in this systematic review. Diffuse large B-cell lymphoma was the predominant morphological subtype observed. The rituximab, cyclophosphamide, doxorubicin, oncovin, and prednisolone regimen emerged as the most commonly employed treatment strategy, indicating widespread acceptance and efficacy in PCL management. Combination therapies, including surgical intervention, showed promise in achieving complete remission, while some studies reported mortality despite aggressive treatment approaches.

CONCLUSION

Rituximab, particularly in combination with chemotherapy regimens, represents a significant advancement in PCL management, offering hope for improved patient outcomes. However, challenges such as variable treatment responses and adverse events underscore the complexity of managing PCL. Further research is warranted to refine therapeutic strategies and enhance diagnostic approaches for this rare cardiac malignancy.

Key Words: Primary cardiac lymphoma; Oncology; Review; Rituximab; B cell lymphoma

Core Tip: This systematic review highlights the efficacy of rituximab-based regimens, particularly rituximab, cyclophosphamide, doxorubicin, oncovin, and prednisolone, in managing primary cardiac lymphoma, a rare and aggressive malignancy. Diffuse large B-cell lymphoma is the most common subtype, and combination therapies, including surgical intervention, show promise in achieving complete remission. However, variability in treatment responses and the risk of adverse events remain significant challenges. Enhanced diagnostic methods and further research are essential to optimize therapeutic strategies and improve outcomes for patients with this rare cardiac tumor.

INTRODUCTION

Primary cardiac tumors are a very rare entity comprising only 0.02% of all tumors[1] and rarer still is the primary cardiac lymphoma (PCL) which shows an occurrence of 1% to 2% of these primary cardiac tumors[2], which stands to show that PCL is often overlooked when looking for a diagnosis of the patient. PCL shows an increased occurrence in immunocompromised people such as acquired immunodeficiency syndrome (AIDS) patients or those who have undergone transplant surgeries[3]. PCL shows a predominance for the pericardium and the right side of the heart. Left sided PCL is very rare and bilateral PCL is even rarer still[4]. The most commonly encountered morphological type of PCL is diffuse large B-cell lymphoma (DLBCL) however some other types such as Burkitt lymphoma, B lymphoblastic lymphoma and T cell lymphomas may also be encountered[5-7]. The diagnosis is often made late in the disease because the symptoms of PCL mimic other commonly occurring heart diseases. Therefore, the prognosis of the disease is often poor and it is only picked up in the later stages. There is much work needed to be done in improving the diagnostic modalities for PCL[2]. The definitive diagnosis in the cases of PCL is made on the basis of pathological studies. The most accessible method for the obtaining of samples for the pathological studies is trans esophageal echocardiography-guided trans jugular biopsy[8], This method shows 100% success and carries relatively low risk of developing complications in the patients such as tamponade, arrhythmias, tumor embolization, damage to the valves, vasovagal reactions and pneumothorax[9,10].

The effective treatment of PCL depends on an accurate and early diagnosis coupled with the appropriate and aggressive antilymphoma therapy and it can help prolong the life of the patient[11]. Polychemotherapy appears to be the most suited mode of treatment although the prognosis continues to be poor. Rituximab has been shown to have a significant advantage in the treatment of PCL when it is combined with other chemotherapeutic drugs. Rituximab has been recommended on the basis of its successful utilization in the eradication of PCL in patient[12-14]. Rituximab is a humanized chimeric CD20 antibody that is a powerful tool in targeting the B-cell malignancies that show CD20⁺ cancel cells[15]. The drug binds the CD20⁺ cells and causes the death of the cancer cells with multiple mechanisms, including both direct and indirect methods. The direct methods involve complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity which help kill cells effectively while the indirect methods operate via structural changes, apoptosis and by the sensitization of the cancer cells to the effects of chemotherapy. The sensitization effect of rituximab is taken advantage of by combining it with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone) in the treatment of PCL which has yielded astounding results[12,14,15]. However, not all individuals respond equally to the cancer-killing effects of rituximab[15]. One possible mechanism of this is attributed to the anti-complement inhibitors CD55 and CD59 which provide a mechanism of resistance. Nevertheless, rituximab is a game changer as a part of the polychemotherapy regimen currently recommended for the treatment of PCL[16].

MATERIALS AND METHODS

Search strategy

This study followed the PRISMA and AMSTAR guidelines for systematic reviews, ensuring transparency and methodological rigor. We conducted a thorough literature search across major databases known for their comprehensive coverage of medical and scientific literature, including PubMed, Embase, Web of Science, and Scopus. These databases were selected for their extensive collection of peer-reviewed articles, providing a strong basis for our systematic review of the efficacy of rituximab in the treatment of PCL.

Our search strategy utilized carefully chosen keywords and phrases aligned with our study objectives. Keywords such as "rituximab" and "primary cardiac lymphoma" were employed, and Boolean operators "AND" and "OR" were used to refine the search algorithm. To ensure relevance, our search was limited to studies published from the inception of each database to January 2024. This timeframe allowed us to incorporate both historical and contemporary research on the efficacy of rituximab in the treatment of PCL. We included studies published in English and involving human subjects. Additionally, manual searches of reference lists and relevant reviews complemented the electronic database search.

Eligibility criteria

Stringent eligibility criteria were established to ensure precision in study selection. Only case reports, case series, clinical trials and cohorts reporting the use of rituximab for the treatment of PCL, either as a single drug or in combination regimen, were considered for inclusion. We focused on studies published in English, acknowledging its dominance in scientific communication. Exclusion criteria were carefully defined to maintain focus. Studies not directly addressing the efficacy of rituximab in the treatment of PCL, lacking relevant outcome measures, or not in English were excluded. Unpublished works and gray literature were also excluded, ensuring the integrity of our findings.

Study selection

The process of selecting studies was carried out in two stages. Initially, two independent reviewers examined the titles and abstracts of all identified records to exclude studies that were not relevant. Next, the full texts of the remaining potentially eligible studies were obtained and assessed against the predetermined inclusion and exclusion criteria. Any disagreements between the reviewers were resolved through discussion or by consulting a third reviewer.

Data extraction

Two independent reviewers used a standardized data extraction template within Microsoft Excel to capture and organize critical information from each study. The extracted information included authors, publication year, study design, country, sample size, patient age and sex, type of PCL, key diagnostic findings, intervention and prognosis. Any discrepancies were resolved through the adjudication of a third reviewer.

Quality assessment

The quality assessment of the included studies was performed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and Case Series. The assessment evaluated various aspects of the case reports, such as the clear description of patient demographics, clinical condition, diagnostic tests, interventions, post-intervention outcomes, identification of adverse events, and the provision of takeaway lessons. The case series were assessed based on criteria like clear inclusion criteria, standardized condition measurement, valid identification methods, complete participant inclusion, demographic and clinical condition reporting, outcome reporting, and appropriate statistical analysis. The JBI appraisal scores were calculated, and the quality of the studies was categorized as high, medium, or low based on the percentage of criteria met. This rigorous quality assessment process ensured the inclusion of high-quality evidence and provided a comprehensive evaluation of the methodological strengths and weaknesses of the included studies (Supplementary Tables 1-7).

RESULTS

Study selection process

Following the PRISMA guidelines, a thorough search across relevant databases initially yielded 422 potential studies. After removing 87 duplicates, 335 unique studies remained for consideration. Subsequent screening of titles and abstracts was conducted to assess relevance to the predetermined inclusion criteria, resulting in the exclusion of 288 records. Full-texts of 9 studies could not be retrieved. Full-text evaluation of the remaining 47 articles was then undertaken, leading to the exclusion of 5 reports that did not meet the stringent inclusion criteria. Through this rigorous selection process, 33 studies were identified as suitable for inclusion in the systematic review, offering a focused and robust source of evidence. This study selection process is illustrated in the PRISMA flowchart (Figure 1).

Figure 1 PRISMA flow diagram of selection of studies for inclusion in the systematic review.

Study characteristics

This review encompasses total of 33 studies (31 case reports and 2 case series) reporting the effect of rituximab in its various regimens in a total of 36 patients[5,6,13,14,17-44]. Among these 36 patients 22(61.11%) were male and 14(38.89%) were females, underscoring the male predominance of patients with PCL. The age of the patients in the study ranged from 28 to 85 years, with a mean age of 67 years, highlighting diverse age distribution of the disease (Table 1).

Table 1 Characteristics of the studies included in this systematic review.

Ref.	Country	No. of patients	Gender	Age (years)
Ellen and Emma[17], 2023	Ireland	1	Female	78
Qiang et al[18], 2022	China	1	Male	71
Mao et al[19], 2023	China	1	Male	64
Fuseya et al[20], 2021	Japan	1	Male	54
Miyawaki et al[21], 2021	Japan	1	Male	55
Fukuzaki et al[22], 2022	Japan	1	Female	68
Mandal et al[13], 2019	Cyprus	1	Male	83
Bonou et al[23], 2019	Greece	1	Male	28
Anand et al[24], 2019	United States	1	Male	69
Ito et al[25], 2018	Japan	1	Male	79
Endo et al[26], 2018	Japan	1	Male	79
Mendelson et al[27], 2018	United States	1	Male	79
Annibali et al[28], 2018	Italy	1	Male	80
Quiroz et al[29], 2018	United States	1	Female	85
Rogers et al[30], 2016	United States	1	Male	72
Soon et al[31], 2016	Singapore	3	Female; Female; Male	80F; 75F; 59M
Yamamoto et al[32], 2016	Japan	1	Male	65
Montanaro et al[33], 2015	United States	1	Male	71
Khan-Kheil et al[34], 2015	United Kingdom	1	Male	71
Pires Ferreira Filho et al[5], 2015	Brazil	1	Male	52
Nose et al[35], 2014	Japan	1	Female	80
Habertheuer et al[36], 2014	Austria	1	Female	70
Tzachanis et al[6], 2014	United States	1	Female	44
Menke et al[37], 2012	Germany	1	Male	56
Gadage et al[38], 2011	India	1	Male	38
Bambury et al[39], 2011	Ireland	1	Female	70
Shin et al[40], 2010	Korea	1	Male	59
Fujita et al[41], 2009	Japan	1	Male	56
Nonami et al[12], 2007	Japan	1	Female	55
Trost et al[42], 2007	United States	1	Female	83
Dawson et al[14], 2006	Australia	1	Female	76
Bley et al[43], 2005	Germany	1	Female	76
Anghel et al[44], 2004	Italy	2	Male; Female	52M; 70F

The most common morphological subtype of PCL was found to be DLBCL, established as final diagnosis in 32 (88.89%) out of 36 cases. The other morphological subtypes were found to be Burkitt lymphoma and B lymphoblastic lymphoma accounting for one case each. Morphological subtype of PCL was unspecified in 2 cases. Rituximab, cyclophosphamide, doxorubicin, oncovin, and prednisolone (R-CHOP) was solely administered in 14 studies, out of which 10 reported complete remission. Out of the remaining 4, there were 2 studies that reported partially remission and 2 studies reported adverse outcomes after administration of sole R-CHOP regimen. Five studies involved the use of surgical intervention along with the administration of R-CHOP all reporting complete remission. A study also reported favorable prognosis after administration of R-HDS followed by stem cell transplantation. Combination chemotherapy consisting of regimes such as R-CDOP, R-COP, R-CVP, R-CHASE, R-EPOCH and R-HYPER-CVAD in various combinations were also employed in various studies. Among these studies 6 reported complete remission while 3 reported mortality even after the administration of combined chemotherapy (Table 2).

Table 2 Summary of the main findings of the studies included in the review.

Ref.	Primary diagnosis	Key diagnostic findings	Intervention	Prognosis
Ellen and Emma[17], 2023	DLBCL	TTE showed mass in LA	R-CHOP (6 cycles)	CR
Qiang et al[18], 2022	DLBCL	CT and TTE showed solid lesion in the LA	R-CDOP for 4 months	CR
Mao et al[19], 2023	DLBCL	CT revealed a soft tissue density shadow in the pericardium	R-COP regimen administered for 1 day; pacemaker implantation; R-CDOP regimen	PR
Fuseya et al[20], 2021	DLBCL	CT revealed tumor in RA, outside the right atrial wall and ventricle	Rituximab under VA-ECMO; R-CHOP therapy 9 days post-VA-ECMO initiation; CHOP therapy (6 cycles)	Death due to progression of the disease
Miyawaki et al[21], 2021	Subtype unspecified	CT and TTE showed a cardiac tumor involving the right side of the heart	Aspirin and COP; R-CHOP (3 cycles); R- CHASE (5 cycles)	CR
Fukuzaki et al[22], 2022	DLBCL	Echo showed mass in RA and RV	R-CHOP (6 cycles)	PR
Mandal et al[13], 2019	DLBCL	CT and TTE revealed mass in RA	Staggered R-CVP (8 cycles)	CR
Bonou et al[23], 2019	DLBCL	TTE revealed mass infiltrating the interatrial septum	R-CHOP over 15 days; pacemaker insertion	CR
Anand et al[24], 2019	DLBCL	CMRI showed large mass involving RV	Dose-adjusted R-EPOCH; biventricular pacemaker	CR
Ito et al[25], 2018	DLBCL	CT revealed a mass adjacent in the aortic root	Pacemaker placement; R-CHOP, without	Death
Endo et al[26], 2018	DLBCL	TTE revealed a mobile tumor in RA	MICS; R-CHOP therapy (8 cycles)	CR
Mendelson et al[27], 2018	DLBCL	CT revealed large mediastinal mass, a soft-tissue mass within the RA	IV methylprednisolone; R-CHOP (2 cycles); doxorubicin	PR
Annibali et al[28], 2018	DLBCL	MRI showed huge soft tissue mass in right heart	Surgical removal of a portion of pericardium; R-CVP (6 cycles)	CR followed by CNS relapse and death
Quiroz et al[29], 2018	DLBCL	B-cells on flow cytometry	Pericardiocentesis; R-CHOP	CR
Rogers et al[30], 2016	DLBCL	MRI showed dense mass involving the RV and RA	EPOCH-R	PR followed by decline in health
Soon et al[31], 2016	DLBCL	Case 1: TTE and CT: Mass in the anterior AV groove; Case 2: MRI: Large infiltrative mass involving RA/RV, inferior wall of LV; Case 3: MRI: Large infiltrative pericardial/epicedial mass, involving RA/LA/RV/LV	Case 1: R-CEPP (6 cycles). Case 2: R-CVP (5 cycles). Case 3: R-CHOP (6 cycles)	CR; PR and relapse; CR
Yamamoto et al[32], 2016	DLBCL	CT revealed a large mass in the RA and RV	Surgery; Cardiopulmonary bypass; R-CHOP	CR
Montanaro et al[33], 2015	DLBCL	TTE & TEE revealed severe pericardial effusion	Pleural effusion drained; Pacemaker implanted; R-CHOP (6 cycles)	CR
Khan-Kheil et al[34], 2015	Subtype unspecified	CMRI showed a large multilobulated mass	Effusion drained; R-CHOP (8 cycles)	CR
Pires Ferreira Filho et al[5], 2015	DLBCL	Echo revealed RA mass	R-hyper-CVAD; methotrexate and cytarabine plus rituximab	CR followed by recurrence and death
Nose et al[35], 2014	DLBCL	Enhanced CT revealed a tumor invading into the RV	Transvenous pacing electrode insertion; R-CHOP (every 3 weeks)	CR
Habertheuer et al[36], 2014	DLBCL	TTE revealed soft tissue density in both atrium and ventricle	Surgical excision; cardiopulmonary bypass, and pericardial patch implantation; R-CHOP (6 cycles)	CR
Tzachanis et al[6], 2014	Primary burkitt lymphoma	Pericardial effusion (CT). Pericardial effusion showed B cells characteristic of Burkitt lymphoma	Modified CODOX-M (4), IVAC, and rituximab	CR
Menke et al[37], 2012	DLBCL	Cardiac mass on MRI. Multiple atypical lymphoid cells with large nuclei	R-CHOP (at 14-day intervals); Rituximab immunotherapy	CR
Gadage et al[38], 2011	DLBCL	Biopsy and histology revealed a large B cell population	R-CHOP (4 cycles)	Remission followed by relapse and death
Bambury et al[39], 2011	DLBCL	MRI revealed soft tissue mass arising from the RV free wall	R-CHOP (every 3 weeks)	CR
Shin et al[40], 2010	DLBCL	TTE showed non-movable ovoid mass. CT showed tumor compressing both atria and part of the LV	R-CHOP (every 3 weeks); RT	PR
Fujita et al[41], 2009	DLBCL	TTE showed a large mass occupying both the RV and RA	Surgical removal; R-CHOP	CR
Nonami et al[12], 2007	DLBCL	CT revealed mass in the RA and RV chambers. Pleural effusion cytology revealed increased abnormal lymphocytes	Reduced-dose CHOP; R-CHOP (6 cycles); Autologous PBSCT	CR
Trost et al[42], 2007	DLBCL	TEE revealed a mass near the RV	R-CHOP	CR
Dawson et al[14], 2006	DLBCL	CT, MRI and TTE confirmed an intramyocardial mass involving right atrium	R-CHOP (4 cycles) for 14 days	CR
Bley et al[43], 2005	DLBCL	Catheter guided biopsy confirmed DLBCL	R-CHOP (6 cycles)	PR (tumor size shrunken to 10% of original one)
Anghel et al[44], 2004	DLBCL	Transesophageal biopsy confirmed DLBCL	R-HDS, autologous PBSCT; pericardiocentesis, cyclophosphamide, and vincristine	CR; died after 2 weeks

DLBCL: Diffuse large B-cell lymphoma; R-CDOP: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; R-COP: Rituximab, cyclophosphamide, vincristine (oncovin), and prednisolone; VA-ECMO: Veno-arterial extracorporeal membrane oxygenation; R-CHOP: Rituximab, cyclophosphamide, doxorubicin, oncovin, and prednisolone; R-CHASE: Rituximab, cyclophosphamide, cytosine arabinoside, etoposide, and dexamethasone; COP: Cyclophosphamide, vincristine (oncovin), prednisone; R-CVP: Rituximab, cyclophosphamide, vincristine sulfate, and prednisone; RA: Right atrium; RV: Right ventricle; LA: Left atrium; LV: Left ventricle; TTE: Transthoracic echocardiogram; R-EPOCH: Rituximab, etoposide phosphate, prednisone, vincristine sulfate (oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin); MICS: Minimally invasive heart surgery; EPOCH-R: Etoposide phosphate, prednisone; vincristine sulfate (oncovin), cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin), rituximab; TEE: Transesophageal echocardiogram; CR: Complete remission; PR: Partial remission; RT: Radiotherapy; R-CEPP: Rituximab, cyclophosphamide, etoposide, procarbazine, and prednisone; CT: Computerized tomography; R-hyper-CVAD: Rituximab-hyper-cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (adriamycin), and dexamethasone; Echo: Echocardiogram; MRI: Magnetic resonance imaging; CODOX-M: Cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate; IVAC: Ifosfamide, etoposide, and high-dose cytarabine; PBSCT: Peripheral blood stem cell transplant; CMRI: Cardiovascular magnetic resonance imaging; R-HDS: High-dose sequential chemotherapy and rituximab.

Quality assessment

The quality assessment of the included studies using the JBI Critical Appraisal Checklist for Case Reports and Case Series ensured the inclusion of high-quality evidence and provided a comprehensive evaluation of the methodological strengths and weaknesses of the included studies (Supplementary material). 29 case reports were of high quality, 2 were of medium quality and one was of low quality. Both the case series were of high quality.

DISCUSSION

The management of PCL, a rare and aggressive malignancy primarily affecting the right side of the heart, presents substantial diagnostic and therapeutic challenges[17]. Due to its rarity and nonspecific clinical manifestations, timely diagnosis of PCL remains elusive[18], thereby confounding treatment initiation and prognostic outcomes. Left untreated, PCL portends a dismal prognosis, underscoring the critical imperative for expeditious intervention upon suspicion or confirmation of diagnosis[45]. Notably, the histopathological characterization of PCL predominantly reflects features consistent with non-Hodgkin lymphoma[5], emphasizing its lymphoid origin and inherent heterogeneity. Against this backdrop, the advent of rituximab, a monoclonal antibody targeting the CD20 antigen expressed on B-cells, heralds a paradigm shift in the therapeutic landscape of PCL[46]. The introduction of rituximab has engendered notable improvements in PCL management, facilitating enhanced disease control and ameliorated prognostic trajectories[40]. By selectively targeting malignant B-cells, rituximab mitigates tumor burden and augments treatment response rates, thereby conferring a tangible clinical benefit to afflicted individuals[47]. Furthermore, the favorable safety profile and tolerability of rituximab render it an indispensable component of multimodal therapeutic regimens aimed at optimizing PCL outcomes.

Studies investigating the efficacy of the R-CHOP regimen, a standard chemotherapy protocol comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, have yielded mixed results. Among these, 14 studies focused solely on R-CHOP, with 10 of them reporting remission post-treatment, indicating a favorable prognosis[14,17,23,29,33-35,37,39,42]. Additionally, some studies noted a reduction in tumor size following R-CHOP administration[22,27,43]. However, adverse outcomes were also documented. Gadage et al[38] reported disease relapse after six weeks of R-CHOP therapy, while Ito et al[25] observed patient death despite tumor size reduction attributed to R-CHOP. In the latter case, chemotherapy-induced leukocytopenia led to pyothorax, highlighting potential complications associated with this regimen.

Incorporating surgical intervention alongside R-CHOP was explored in five studies, all reporting complete remission post-intervention[12,26,32,36,41]. This combination approach seems promising in achieving favorable outcomes for PCL patients. This integrated approach underscores the importance of a multidisciplinary treatment strategy tailored to individual patient needs and disease characteristics. However, the optimal timing and extent of surgical intervention in conjunction with chemotherapy warrant further investigation to maximize treatment efficacy and minimize potential risks. In addition to R-CHOP, alternative treatment modalities have been explored, including R-HDS chemotherapy followed by autologous stem cell transplantation. Anghel et al[44] reported positive outcome in a patient who received R-HDS chemotherapy followed by autologous stem cell transplantation and also reported the death of a female who received combined chemotherapy after presentation with cardiac tamponade. Such mixed outcomes highlight the need for continued research to elucidate their role in PCL management.

In addition to R-CHOP various other chemotherapy regimens were employed in PCL. These include R-CDOP, R-COP, R-CVP, R-CHASE, R-EPOCH, and R-Hyper-CVAD. Each regimen combines rituximab with different chemotherapeutic agents, providing clinicians with tailored options suited to the patient's lymphoma type and overall health status. Studies assessing combination chemotherapy reported varying outcomes. Six studies achieved complete remission[6,13,18,21,24,30] while three studies resulted in patient mortality despite intervention[5,20,44]. Notably, one study reported tumor size reduction [19], and another exhibited declining health[30] with combination chemotherapy. Fuseya et al[20] identified brain relapse as the cause of death in their study, while Pires Ferreira Filho et al[5] reported death due to disease relapse associated with cardiac failure after combined chemotherapy. These findings underscore the complexity of PCL treatment and the importance of individualized therapeutic approaches tailored to patient-specific factors and disease characteristics.

The systematic review may have several limitations. Firstly, the inclusion of primarily published case reports and case series could introduce publication bias, potentially underrepresenting cases with atypical presentations or poorer outcomes. This bias could affect the overall conclusions drawn from the review. Additionally, some case reports may lack comprehensive data on diagnostic procedures, treatment modalities, and long-term follow-up, limiting the depth of analysis and understanding. Furthermore, it is crucial to acknowledge the limitations of rituximab-based therapy in PCL management, including the potential for adverse effects such as infusion reactions, cytopenias, and increased risk of infections[20]. Rituximab was implicated in an increased risk of infections, particularly in immunocompromised patients, as evidenced by a case of AIDS-associated PCL treated with rituximab under VA-ECMO and continuous hemodialysis[20]. Additionally, the development of rituximab resistance and disease relapse poses significant challenges in long-term disease control, necessitating the exploration of novel therapeutic strategies and targeted agents.

CONCLUSION

Rituximab-based regimens hold promise in the management of PCL, offering favorable outcomes in terms of disease response and survival. However, the optimal use of rituximab in PCL warrants further exploration through well-designed prospective studies to delineate its role in treatment algorithms and to address existing gaps in knowledge regarding its efficacy, safety, and long-term outcomes. The management of PCL necessitates a nuanced and comprehensive approach, integrating chemotherapy, surgery, and potentially novel therapeutic strategies. Continued research efforts are essential to optimize treatment outcomes, minimize treatment-related morbidity and mortality, and improve overall survival for patients afflicted with this challenging condition.