Immunophenotypic analysis of adult patients with T-cell lymphoblastic lymphoma treated with hyper-CVAD

Figures & data

Figure 1. Immunophenotyping of ETP. Tumor samples from a patient (UPN 6) before induction chemotherapy showed ETP phenotype of CD1a−, CD8−, and CD5dim, in conjunction with expression of stem cell antigen CD34.

Table 1. Patients’ characteristics.

UPN	Age (years)	Sex	PS	LDH	Clinical stage	B symptoms	CNS	Mediastinal tumor	PE	BM	PB
1	19	Male	1	High	IV	−	−	+	+	+	+
2	30	Female	3	High	IV	−	−	+	+	+	+
3	29	Female	0	High	IV	−	−	−	−	+	+
4	31	Male	0	Normal	IV	−	−	+	+	−	−
5	55	Female	0	Normal	IV	−	−	+	+	−	−
6	35	Male	1	High	IV	+	−	+	+	−	−
7	68	Male	0	High	I	−	−	−	−	−	−
8	18	Male	3	High	I	+	−	+	+	−	−

Abbreviations: BM, bone marrow; B symptoms (present or absent of night sweat, more than 10% weight loss over 6 months, or recurrent fever >38.3°C); CNS, central nervous system; LDH, lactate dehydrogenase; PB, peripheral blood stem cells; PS, performance status; PE, pleural effusion; UPN, unique patient number.

Table 2. Immunophenotypic analysis of tumor cells.

UPN	CD1a	CD2	cCD3	sCD3	CD4	CD5	CD7	CD8	CD33	CD34	CD56	CD57	TdT	CD19	CD20	CD79a
1	+	−	+	−	dim	+	+	+	−	−	−	−	+	−	NE	+
2	−	+	+	dim	−	+	+	−	−	−	−	−	+	−	−	NE
3	+	+	+	dim	+	+	+	−	−	−	−	+	+	−	−	+
4	+	+	+	−	+	+	+	+	−	NE	−	dim	+	NE	−	NE
5	−	+	+	+	−	+	+	−	NE	+	NE	NE	+	NE	−	−
6	−	−	+	−	−	dim	+	−	−	+	+	−	+	+	−	+
7	−	+	+	−	−	+	+	dim	−	dim	+	−	+	NE	−	−
8	+	+	+	−	−	+	+	+	−	−	+	+	+	NE	−	NE

Abbreviations: CD, cluster of differentiation; cCD3, cytoplasmic CD3; NE, not evaluated; sCD3, surface CD3; UPN, unique patient number.

Table 3. Treatment results according to immunophenotype data on T-ALL/LBL.

Authors and year	Diseases	Immunophenotypes	Patients		Median age	Treatment (protocol)	CR		Induction failure		OS		DFS/EFS		Reference No.
			n	%	years (range)
Children and adolescents
Reiter et al. (2000)	LBL		105		8.8 (1.1–16.4)	NHL-BFM-90									[8]
		Pro-/pre-T-cell		10									82% (EFS at 5 years)	NS
		Intermediate T-cell		40									93% (EFS at 5 years)
		Mature T-cell		6									100% (EFS at 5 years)
		T-cell, not further specified		44									91% (EFS at 5 years)
van Grotel et al. (2008)	ALL		72			DCOG ALL-7, ALL-8, or ALL-9									[9]
		Pro-/pre-T		33	6.8 (1.1–13.4)								79% (DFS at 5 years)	NS
		Cortical T		42	7.1 (1.5–15.9)								68% (DFS at 5 years)
		Mature T		25	7.3 (1.8–16.7)								65% (DFS at 5 years)
Coustan-Smith et al. (2009)	ALL		139		8.8 (0.5–18.9)	Total therapy studies XIII, XIV, and XV									[3]
		ETP		12							19% (at 10 years)	p < 0.0001	22% (EFS at 10 years)	p < 0.0001
		Non-ETP		88							84% (at 10 years)		69% (EFS at 10 years)
Patel et al. (2012)	LBL		142		Children and adolescents	COG A5971									[7]
		Early T		11									Median EFS: NR	p = 0.073
		Non-early T		89									Median EFS: NR
Inukai et al. (2012)	ALL		91		(1–18)	TCCSG L99–15									[11]
		ETP		5									40.0% (EFS at 4 years)	p = 0.014
		Typical T		95									70.9% (EFS at 4 years)
Patrick et al. (2014)	ALL		222		(1–24)	MRC UKALL2003									[12]
		ETP		16							82% (at 5 years)	p = 0.1	77% (EFS at 5 years)	p = 0.2
		Typical T		84							91% (at 5 years)		85% (EFS at 5 years)
Kobayashi et al. (2014)	ALL and LBL		77		(2–15)	JACLS NHL T-98 or ALL T-97									[10]
		Immature*		52							86% (at 10 years)	p = 0.0547	73% (EFS at 10 years)	p = 0.2525
		Mature*		48							68% (at 10 years)		60% (EFS at 10 years)
Madanat et al. (2016)	ALL		63			A modified St. Jude total XV									[13]
		ETP		21	10.8 (3.3–14.4)						77% (at 5 years)	p = 0.823	80% (EFS at 5 years)	p = 0.3812
		non-ETP		79	9.25 (0.58–17.7)						79% (at 5 years)		65% (EFS at 5 years)
Children, adolescents, and adults
Vitale et al. (2006)	ALL		90		26.6 (14.0–51.8)	GIMEMA LAL 0496									[14]
		Pre-/pro-T		51			56%	p = 0.002
		Cortical/mature		49			91%
Neumann et al. (2012)	ALL		178		(15–65)	GMALL 05/93, 06/99, 07/03 trials									[15]
		ETP		32			79%	p = 0.65			35% (at 10 years)	p = 0.60	46% (CR duration at 9 years)	p = 0.16
		Non-ETP early T		68			82%				38% (at 10 years)		57% (CR duration at 9 years)
Van Vlierberghe et al. (2013)	ALL		53		Adults	ECOG E2993									[16]
		Early immature		53							34% (at 5 years)	p = 0.0112
		Cortical/mature		47							62% (at 5 years)
Allen et al. (2013)	ALL and LBL		48		13 (0.7–81)	DFCI, COG, CALGB, NY-I, NY-II, or others									[17]
					[18 or under]
		ETP		11	9.8				25%	NS
		Non-ETP		89	8.9				21%
					[over 18]
		ETP		30	40				33%	p = 0.3
		Non-ETP		70	52				0%
Shimizu et al. (2013)	ALL		36			JALSG ALL90, ALL93, ALL97, or ALL202									[18]
		Pro-/pre-T		61	32 (16–72)		45%	p = 0.04			27% (at 3 years)	p = 0.66	19% (DFS at 3 years)	p = 0.49
		Cortical/medullary		39	33 (17–66)		79%				38% (at 3 years)		32% (DFS at 3 years)
Chopra et al. (2014)	ALL		69			INCTR, BFM-90, or hyper-CVAD									[19]
		ETP		13	22 (12–53)						77.5% (at 60 days)	p = 0.005	37.6% (EFS at 60 days)	p = 0.002
		Non-ETP		87	11 (1.5–48)						96.6% (at 60 days)		80.8% (EFS at 60 days)
Jain et al. (2016)	ALL and LBL		111		30 (13–79)	Hyper-CVAD and others									[20]
		ETP		17			73%	p = 0.03			Median OS: 1.7 years	p = 0.008	Median EFS: 1.2 years	p = 0.17
		Non-ETP		83			91%				Median OS: NR		Median EFS: NR
Brammer et al. (2017)	ALL		88		31 (2–72)	Hyper-CVAD and others									[21]
		ETP		18							29% (at 3 years)	NS
		Pro-/pre-T		32							41% (at 3 years)
		Cortical T		31							27% (at 3 years)
		Mature T		19							31% (at 3 years)
The current study	LBL		8		31 (18–68)	Hyper-CVAD
		ETP		12.5					100%	p = 0.064
		Non-ETP		87.5					14%

Abbreviations: ALL, acute lymphoblastic leukemia; BFM, Berlin-Frankfurt-Munster; CALGB, Children’s Oncology Group (COG), Cancer and Leukemia Group regimen B; CD, cluster of differentiation; CI, cumulative incidence; COG, the Children’s Oncology Group; CR, complete remission; DCOG, Dutch Childhood Oncology Group; DFCI, Dana Farber Cancer Institute; DFS, disease-free survival; ECOG, the Eastern Cooperative Oncology Group; EFS, event-free survival; ETP,early T-precursor; GIMEMA, the Gruppo Italiano Malattie Ematologiche dell’Adulto; GMALL, the German Multicenter Study Group for Adult ALL; INCTR, International Network for Cancer Treatment & Research; JALSG, the Japan Adult Leukemia Study Group; LAL, leucemia acuta limfoide; LBL, lymphoblastic lymphoma; MRC, the Medical Research Council; NHL, non-Hodgkin’s lymphoma; NR, not reached; NS, not significant; NY-I, NY-II, Memorial Sloan Kettering; OS, overall survival; TCCSG, the Tokyo Children’s Cancer Study Group.

*Immature: CD7+(CD2+ or CD5+)CD3−.

*Mature: CD7+CD2+CD5+CD3+.

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