Original Article

Anaplastic large cell lymphoma: A single institution experience from India ABSTRACT Background: Systemic anaplastic large cell lymphoma (ALCL) accounts for 2-8% of non-Hodgkin’s lymphoma in adults and 10-15% in children. While there is ample data in the world literature about the clinical features and outcome of this disease, prognosis in Indian patients is largely unknown. Objective: To study the clinical, pathologic profile and outcome ALCL. Materials and Methods: Fifty patients who had pathologically proven diagnosis of systemic ALCL at our institute from June 2003 to May 2011 were included for retrospective analysis. This included 30 cases of anaplastic lymphoma kinase+ (ALK+), ALCL and 20 cases of anaplastic lymphoma kinase- (ALK−), ALCL. The hospital protocol for treatment of these patients included CHOP chemotherapy regimen in >15 years of age and MCP842 protocol with vinblastine for 1 year in 15 years of age and MCP (multicentric protocol) 842 protocol with vinblastine maintenance in 1 lymph node region. Splenomegaly was seen in 12 cases (ALK+, 9; ALK−, 3). Extranodal involvement was seen in 24 (48%) cases; of which 11 cases (ALK+, 7; ALK−, 4) presented as a primary extranodal disease. The details of the extranodal sites involved are given in Table 2. In the morphological subtypes, the classic pleomorphic pattern was the most common histological subtype noted in both ALK+ and ALK− groups, as shown in Table 3. Table 4 shows the IHC marker positivity in both the subtypes of ALCL, with CD3 positivity more common in ALK− ALCL, and EMA positivity more common ALK+ ALCL. 650

Table 1: Clinical features Features Sex Male Female Age ≤30 years >30 years Splenomegaly Performance status 0-2 3-4 B symptoms Primary presentation as extranodal disease Only nodal disease LDH value>normal range Ann Arbor stage I/II III/IV International prognostic index 0-2 ≥3

ALCL, ALK+ (pos.) (n=30) (%)

ALCL, ALK− (neg.) (n=20) (%)

21 9

13 07

27 3 9 (30)

07 13 03 (15)

25 (83) 05 (17) 20 (67) 07 (23)

15 (75) 05 (25) 12 (60) 04 (20)

18 (60) 10 (33)

12 (60) 07 (35)

11 (37) 19 (63)

10 (50) 10 (50)

22 (73) 08 (27)

15 (75) 05 (25)

ALCL = Anaplastic large cell lymphoma, ALK+ = Anaplastic lymphoma kinase+, ALK− = Anaplastic lymphoma kinase−, LDH = Lactate dehydrogenase

Table 2: Extranodal sites of involvement in ALCL, ALK+ and ALK− Extranodal site Bone Skin Lung (major bronchus) GIT Soft tissue Orbit Oral cavity

ALK+ 05 04 01 01 01 -

ALK− 02 05 02 01 01 01

ALCL = Anaplastic large cell lymphoma, ALK+ = Anaplastic lymphoma kinase+, ALK− = Anaplastic lymphoma kinase−, GIT = Gastrointestinal tract

Table 3: Morphologic subtypes of ALCL, ALK+ and ALK− Subtypes Classic Small cell Lymphohistiocytic Spindle cell Signet ring Hodgkin like

ALCL, ALK+ (n=30) 27 01 01 01 -

ALCL, ALK− (n=20) 18 01 01

ALCL = Anaplastic large cell lymphoma, ALK+ = Anaplastic lymphoma kinase+, ALK− = Anaplastic lymphoma kinase−

Table 4: Immunohistochemistry IHC marker positivity CD30 (n=50) ALK (n=50) LCA (n=22) CD3 (n=38) EMA (n=38) LMP (n=31) CD4 (n=31) CD8 (n=32)

ALCL, ALK+ (%) 30/30 (100) 30/30 (100) 13/14 (93) 04/21 (19) 18/21 (86) 0/20 17/20 (85) 01/21 (05)

ALCL, ALK− (%) 20/20 (100) 0/20 07/08 (88) 10/17 (59) 8/17 (47) 02/11 (18) 10/11 (91) 01/11 (09)

P value (ALK+vs. ALK−) 1 15 years. Both used different protocols. The outcomes in both these patients are given in Figures 1 and 2 respectively. At the median follow-up of 36 months, the EFS in pediatric ALCL was 66.7%, 60% in adult ALK+ ALCL and 20% in adult ALK− ALCL. Advanced stage (P = 0.01), ALK− ALCL (P = 0.001) and high IPI score (P = 0.03) correlated with poor outcome. DISCUSSION ALCL represents 2% of all non-Hodgkin’s lymphoma.[3] There is scarcity of data in Indian context about this disease. Little is known about the clinical, hematological profile and outcome in our setting. Compared to patients hailing from China and Pakistan, the median age of the presentation was lower with ALK+ ALCL, but similar to those reported in world literature for patients with ALK− ALCL.[4-6] Event Free Survival

VAR00001 EFS in < 15 years EFS in < 15 yearscensored

1.0

Survival probability

0.8 0.6

0.4 0.2

0.0 .00

60.00 20.00 40.00 Time in months

80.00

Figure 1: Event-free survival in patients 15 years, which included both subgroups

We are grateful to the faculty of Department of Medical and Pediatric Oncology, KMIO, Bangalore, 560029. We extend our heartfelt thanks to all the faculty of the department of pathology especially Dr. Clementina Rama Rao, Professor, Department of Pathology.

Journal of Cancer Research and Therapeutics - October-December 2013 - Volume 9 - Issue 4

651

Lakshmaiah, et al.: Anaplastic large cell lymphoma: A single institution experience from India

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the International Peripheral T-Cell Lymphoma Project. Blood 2008;111:5496-504. 7. Filippa DA, Ladanyi M, Wollner N, Straus DJ, O’Brien JP, Portlock C, et al. CD30 (Ki-1)-positive malignant lymphomas: Clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin’s disease. Blood 1996;87:2905-17. 8. ten Berge RL, de Bruin PC, Oudejans JJ, Ossenkoppele GJ, van der Valk P, Meijer CJ. ALK−negative anaplastic large-cell lymphoma demonstrates similar poor prognosis to peripheral T-cell lymphoma, unspecified. Histopathology 2003;43:462-9. 9. Le Deley MC, Rosolen A, Williams DM, Horibe K, Wrobel G, Attarbaschi A, et al. Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: Results of the randomized ALCL99-vinblastine trial. J Clin Oncol 2010;28:3987-93. 10. Brugières L, Pacquement H, Le Deley MC, Leverger G, Lutz P, Paillard C, et al. Single-drug vinblastine as salvage treatment for refractory or relapsed anaplastic large-cell lymphoma: A report from the French Society of Pediatric Oncology. J Clin Oncol 2009;27:5056-61. 11. Foyil KV, Bartlett NL. Brentuximab vedotin and crizotinib in anaplastic large-cell lymphoma. Cancer J 2012;18:450-6. Cite this article as: Lakshmaiah KC, Guruprasad B, Shah A, Kavitha S, Abraham LJ, Govindbabu K, et al. Anaplastic large cell lymphoma: A single institution experience from India. J Can Res Ther 2013;9:649-52. Source of Support: Nil, Conflict of Interest: None declared.

Journal of Cancer Research and Therapeutics - October-December 2013 - Volume 9 - Issue 4

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Anaplastic large cell lymphoma: a single institution experience from India.

Systemic anaplastic large cell lymphoma (ALCL) accounts for 2-8% of non-Hodgkin's lymphoma in adults and 10-15% in children. While there is ample data...
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