Tackling mantle cell lymphoma (MCL): Potential benefit of allogeneic stem cell transplantation

Figures & data

Table 1 First-line MCL regimens

Regimen	Year	n	RR%	CR%	PFS/TTF months
COP versus CHOP^Citation18	1989	37	84	41	7
		26	89	58	10
CHOP versus	2005	122	75	7	14
R-CHOP^Citation15			94	34	21
MCP versus CHOP^Citation19	2006	86	73	20	15
			87	15	21
R-CHOP^Citation14	2002	40	96	48	16.6
R-HyperCVAD-R-M/A^Citation13	2005	97	97	87	36 months FFS 73%
R-CHOP → RIT^Citation20	2007	56	88	55	27 months

Abbreviations: COP, cyclophosphamide-vincristine-prednisone; CHOP, cyclophosphamide-doxorubicin-vincristine-prednisone; MCP, mitoxantrone-chlorambucil-prednisone; RR, response rate; CR, complete response; PFS, progression-free survival; TTF, time to treatment failure; FFS, failure-free survival; HyperCVAD, hyperfractionated cyclophosphamide-vincristine-doxorubicin-dexamethasone; M/A, methotrexate/cytarabine; R, rituximab; R-CHOP, rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone; RIT, radio immunotherapy; MCL, mantle cell lymphoma.

Table 2 Trials employing autologous Stem cell transplant consolidation

Regimen	Year	Author/institution	n	PFS/EFS	Remarks
Hyper-CVAD/MTX-Ara-C → Cy/TBI^Citation25	1998	Khouri/MD Anderson	45	3 yr EFS 42% Median PFS 39 mos	n = 25 1st line
Various^Citation26	2000	Vose/Univ Nebraska	40	2 year EFS 36%
RIT/cy/etop^Citation27	2002	Gopal/Univ WA Seattle	16	3 year PFS 61%	All relapsed
Various^Citation23	2003	Vandenberghe/EBBMT/ABMTR	195	2 year PFS 55% 5 year PFS 33%
CHOP like induction Dexa-BEAM → cy/TBI vs IFNα^Citation21	2005	Dreyling/European MCL network	62 (ASCT)	Median PFS 39 mos (ASCT) vs 17 mos (IFN)	First line
R-maxi-CHOP/HIDAC → BEAM^Citation28	2008	Geisler/Nordic Lymphoma group	160	6 year EFS 56%	First line
R-maxi-CHOP, eto, MTX/HIDAC → CEP, R^Citation7	2008	Hsi/CALGB	52	3 year PFS 52%, EFS 57%	Stratified by Ki-67 and PIM1

Abbreviations: Cy/TBI, cyclophosphamide/total body irradiation; RIT/cy/eto, radioimmunotherapy/cyclophosphamide/etoposide; HIDAC, high-dose cytarabine; BEAM, BCNU/etoposide/cytarabine/melphalan; CHOP, cyclophosphamide–doxorubicin–vincristine–prednisone; MTX, methotrexate; CEP, carmustine–etoposide–cyclophosphamide; mos, months; PFS, progression free survival; EFS, event free survival.

Table 3 Comparison of transplant strategies in indolent NHL and MCL

	Allo	Auto
Graft issues	Tumor free graft	Potential lymphoma contamination; graft purging benefit not yet proven
Mechanism of effect	GVL effect	High dose chemotherapy effect
Toxicity	Acute and chronic GVHD	Lower acute peritransplant morbidity and mortality
Efficacy	Prolonged remission; potential cure	Not generally curative
Graft quality	Healthy donor graft	Damage from prolonged chemotherapy – risk of myelodysplasia
Recipient factors	Limited patient population (age, performance status, comorbidities)	Safer in patients who are older and with comorbidities
Graft collection	Donor availability	Stem cell collection issues in heavily pretreated marrows

Abbreviations: GVL graft versus lymphoma; GVHD, graft-versus-host disease; allo, allogeneic transplant; auto, autologous transplant.

Table 4 Studies of fully myeloablative regimens in mantle cell lymphoma

Regimen	Graft source	Results	n	ORR	CR	Dz
Mostly cy/TBI^Citation36 MD Anderson Cancer Center	All sib donors	3 yr OS and FFP 55%	16		85.7%	11 rel/ref; 5 new Dx
Mostly cy/TBI^Citation37 Johns Hopkins	All T cell depleted bone marrow grafts from matched sib donors	EFS 50% at 25 mos median f/u; 46% TRM; Chronic GVHD 6%	9			7 chemosensitive
Mostly Bu/cy^Citation38 Princess Margaret Hospital	All matched sib donors; 5 BM and 1 PBSCT (non-myeloabl)	Median survival 4.3+ yrs No TRM	6	100%	66%	5 relapse/refractory
Mostly Cy/TBI^Citation39 Univ of Nebraska	88% PBSCT 100% Matched sib donor	5 yr RR 21% 5 yr EFS 44% 5 yr OS 49%	17	65% at D100	65% at D100	All chemosensitive

Abbreviations: Cy/TBI, cyclophosphamide/total body irradiation; OS, overall survival; FFP, freedom from progression; EFS, event free survival; TRM, transplant related mortality; Bu/cy, busulfan/cyclophosphamide; PBSCT, peripheral blood stem cell transplant; ORR, overall response rate; CR, complete response; Dz, disease charecteristics of patient enrolled; mos, months; GVHD, graft-versus-host disease.

Table 5 Results of alloSCT using reduced intensity regimens in mantle cell lymphoma

Regimen	Immuno-suppression	Results	N	CR	Dz
Various – mostly Flu based^Citation42 EBMT registry 2002	Various	OS at 1 yr 38% PFS at 1 yr 31% TRM at 1 yr 46%	22
FCR PFA^Citation43 MD Anderson Cancer Center 2003	Tacrolimus and methotrexate	Event free survival at 3 yrs 82% D100 mortality 0	18 4 MUD 13 MRD	94%	16 with chemosensitive dz
Flu/mel/CD52^Citation44 Univ College London 2004	Cyclosporine T cell – depleting conditioning regimen	OS at 3 yrs 60% PFS at 3 yrs 50%	10		20% NRM at D100 and 3 yrs
Fludarabine and 2 Gy TBI^Citation45 Fred Hutchinson Cancer Center 2004	Cyclosporine/mycophenolate mofetil	DFS 2 yrs 60% OS 2 yrs 65% NRM 2 yrs 24%	33 16 MRD 16 MUD	75%	Relapsed/refractory
Fludarabine +/−2 Gy TBI^Citation46 Fred Hutchinson Cancer Center 2008		5 yr NRM 27% 5 yr OS 58% 5 yr PFS 52%	53 MRD 28 MUD 25
FCR (86%) PFA (14%)^Citation47 MD Anderson Cancer Center 2009	Tacrolimus and methotrexate	Median PFS 60 mos Median OS NR 6 yr act PFS 46% 6 yr OS 53% TRM at 1 yr 9%	35		17% rel/ref 31% CR2 31% CR3

Abbreviations: FCR, fludarabine/cyclophosphamide/high-dose rituximab; PFA, cisplatin/fludarabine/cytarabine; Flu/melCD52, fludarabine, melphalan, alemtuzumab; NRM, nonrelapse mortality; MUD, matched unrelated donor; MRD, matched related donor; Dz, disease charecteristics of patients enrolled; TRM, transplant related mortality; OS, overall survival; PFS, progression free survival; CR, complete response; mos, months.

Table 6 Characteristics of patients with mantle cell lymphoma receiving allogeneic hematopoietic cell transplants from 1998 to 2007 and registered to the CIBMTR

Variable	HLA-matched siblings		Unrelated
	N Eval	n (%)	N Eval	n (%)
Age (years)	525		203
<50		197 (38)		48 (24)
50–59		233 (44)		92 (45)
60–69		89 (17)		59 (29)
≥70		6 (1)		4 (2)
Male	524	421 (80)	203	163 (80)
Year of transplant	525		203
1998		46 (9)		2 (1)
1999		58 (11)		8 (4)
2000		65 (12)		15 (7)
2001		65 (12)		19 (9)
2002		43 (8)		16 (8)
2003		63 (12)		28 (14)
2004		45 (9)		26 (13)
2005		63 (12)		27 (13)
2006		45 (9)		35 (17)
2007		32 (6)		27 (13)
Conditioning regimen intensity	404		180
Myeloablative		213 (53)		84 (47)
Reduced intensity		191 (47)		96 (53)
Overall survival	525		203
100-days		85 (81–88)		78 (72–84)
1 year		65 (61–70)		53 (46–60)
3 years		54 (50–59)		37 (30–45)
Causes of death	230		121
Primary disease		60 (26)		39 (32)
New malignancy		3 (1)		0
GvHD		31 (13)		19 (16)
IPn		5 (2)		5 (4)
Infection		44 (19)		12 (10)
Organ failure		22 (10)		21 (17)
Other causes		48 (21)		20 (17)
Unknown		17 (7)		5 (4)

The data presented here are preliminary and were obtained from the Statistical Center of the Center for International Blood and Marrow Transplant Research. The analysis has not been reviewed or approved by the Advisory or Scientific Committee of the CIBMTR.

Figure 1 Probability of survival after transplants for Mantle Cell NHL 1998–2007.

Figure 2 Probability of survival after transplants for mantle cell lymphoma, 1998–2007 by donor type and conditioning regimen.⁴⁹

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