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

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

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.