Case

Report

T- Cell Prolymphocytic Leukemia - A Rare

Case
Sharmila Ghosh, Suresh H Advani*
Department of Hematologist and Medical Oncology*, Asian Institute of Oncology, SL Raheja Hospital,
Raheja Hospital Marg, Mahim, Mumbai, India
Correspondence to: Dr Sharmila Ghosh, E-mail: sharghosh@rediffmail.com

Abstract
T- cell Prolymhocytic leukemia (T-PLL) is a rare mature post-thymic T-cell malignancy that is usually reported in the
elderly and follows an aggressive course. A 68 year old male presented with a history of weakness and weight loss
of two months duration. Clinical examination revealed pallor, enlarged cervical and axillary lymph nodes and
splenomegaly. He also had a maculo- papular skin rash. There was marked leucocytosis, anemia and
thrombocytopenia (WBC 445 x103/ml, Hb 8.5gm/dl, Platelet 25x10 3/l) with 60% prolymphocytes in the peripheral
blood. Bone marrow was hypercellular with an excess of prolymphocytes. Flow cytometric analysis of the bone
marrow showed positivity for CD2, CD3, CD4, CD5 and CD7.
T- PLL is a rare T cell disorder with characteristic clinical and laboratory features.Currently, no optimal treatment
exists although there has been some success with 2- deoxycoformycin or Campath-1H
Key Words: Prolymphocytes, Leukemia, T cell, Lymphoproliferative

Introduction
T-cell prolymphocytic leukemia (T-PLL) is a rare postthymic T-cell lymphoproliferative disorder with distinct
clinical, immunophenotypic and cytogenetic features. It
accounts for one third of all post thymic T- cell
leukemias. T and B PLL are two distinct diseases with
different clinical and laboratory features. It is generally
resistant to conventional chemotherapy and the median
survival is 7.5 months. [1, 2]
A precise diagnosis of this condition is important in
determining optimum patient management and
treatment.
Here, we present a rare case of T-PLL in an elderly
male who was treated with chlorambucil but was
subsequently lost to follow-up.
Case Report
A 68 year old male presented with a history of
weakness and weight loss of two months duration.
Clinical examination revealed pallor, enlarged cervical
and axillary lymph nodes and splenomegaly. He also
104

had a maculo-papular skin rash. There was marked

leucocytosis, anemia and thrombocytopenia (WBC 445
x10 3/ml, Hb 8.5gm/dl, Platelet 25 x 10 3/l). The
peripheral blood comprised of a uniform population of
cells with 82% prolymphocytes in the peripheral blood.
These cells were moderately sized lymphocytes with a
high nuclear cytoplasmic ratio, moderately condensed
chromatin and a prominent nucleolus. (Fig.1) The
cytoplasm was basophilic, scanty and agranular with
occasional protrusions. Many of the cells had an
irregular and folded nucleus. The bone marrow aspirate
smears were hypercellular with an excess of
prolymphocytes (76%). Flow cytometric analysis on the
bone marrow showed positivity for CD2, CD3, CD4,
CD5 and CD7. All the B cell markers were negative.
Based on the morphologic features and the
immunophenotypic profile, a diagnosis of
prolymphocytic leukemia of T-cell phenotype was made.
The patient was started on chlorambucil but was
subsequently lost to follow up.
Discussion
T-cell PLL is a rare hematologic malignancy that was
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Ghosh et al: T- Cell Prolymphocytic Leukemia - A Rare Case

T-PLL must be distinguished from B-PLL as well as

the other post-thymic T-cell malignancies. Clinical
features such as lymphadenopathy and skin lesions are
found in T-PLL. These along with immunophenotyping
can differentiate T from B-PLL. The differential
diagnosis from other T-cell malignancies is based on
laboratory features such as morphology, histology and
immunophenotyping. (Table 1) [5]

Figure 1: Wright stained blood film of T-PLL. Medium sized

lymphoid cells with irregular nucleus and prominent nucleoli

first described in 1973. [3] It accounts for approximately

3% of the T-lymphocyte disorders. [4] B-PLL and T-PLL
are distinct disease entities with different clinical and
laboratory features. [5] The disease affects adults with a
median age of 65 years. [5] A slight male preference is
noted. Patients usually present with splenomegaly,
lymphadenopathy, hepatomegaly, skin lesions and
marked lymphocytosis. Pleural effusion, ascites and
central nervous system involvement may develop during
the course of the disease. [1,5] The white blood cell
count is markedly raised usually over 100x 103/l and
one third of cases have anemia and thrombocytopenia.
The predominant cell population in the peripheral
blood comprises of lymphoid cells having features of
prolymphocytes. Morphologically, the T prolymphoctes
are smaller than the B prolymphocytes and have more
cytoplasmic basophilia. The nucleus is irregular in half
the cases of TPLL which may be seen as short
indentations or rarely as polylobated nuclei. [5,6] Serum
antibodies to the human T-cell leukemia virus-I and II
have not been detected. [6] In 20% of T-PLL cases, the
cells are smaller with more condensed chromatin. This
is the small cell variant of T-PLL and they behave
similar to the typical cases. [6]

T-PLL cells have a mature post thymic T-cell phenotype

and do not express CD1a and terminal deoxynucleotidyl
transferase (TdT). The cells are positive for CD2, CD5,
CD3 and CD7 (strong). Occasional cases may be CD3/
cyto CD3 negative but the T-cell Receptor-beta/gamma
chain genes are always rearranged.5 A CD4+/CD8phenotype is seen in approximately two-thirds of the
cases, CD4+/CD8+ in about 25% cases and CD4-/
CD8+ expression is less often seen. [1,5] The intensity
of CD52 expression, (seen in normal and neoplastic
lymphoid cells as well as monocytes and macrophages),
is stronger in T-prolymphocytes than normal T cells. [5,6]
This may explain the good response of T-PLL to anti
CD52 therapy.
The recurrent chromosomal abnormality most often
seen in T-PLL is inv (14)(q11;q32). [7] The inversion
(14) results in juxtaposition of a putative oncogene,
TCL-1, located at 14q32.1, a region centromeric to the
immunoglobulin heavy chain locus, with the gene
coding for the TCR-alpha chain at 14q11 resulting in
the expression and activation of TCL-1. Trisomy 8 and
iso 8q are also common in T-PLL and is associated
with c-myc overexpression. High expression of c-myc
may play a role in disease progression as a secondary
event. [5]
T-PLL is an aggressive disorder with a median survival
of seven months. Currently there is no approved
standard treatment for T-PLL. Treatment with alkylating
agents such as chlorambucil has been disappointing as
patients are either resistant or achieve only a partial or

Table 1: Differential diagnosis of T-PLL

Feature

T-PLL

LGL Leukemia

Sezary Syndrome

Morphology
Phenotype

ATLL

Prolymphoctye

LGL

Cerebriform

Flower cell

CD4+CD8, CD4+CD+

CD8+CD4-, NK cell markers

CD4+CD8-

CD4+CD8-

Histology:Spleen

Red/white pulp

Red pulp

Skin

Dermal

Dermal & epidermal

Dermal & epidermal

HTLV-1

Neg

Neg

Neg

Positive

Clinical course

aggressive

indolent

chronic

aggressive

LGL= large granular cell, ATLL = adult T- cell leukemia lymphoma, NK cell= Natural killer cell
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Ghosh et al: T- Cell Prolymphocytic Leukemia - A Rare Case

short lived response. Although about one third of

patients respond to CHOP chemotherapy
(cyclophosphamide,
doxorubicin,
vincristine,
prednisone), eventually the disease recurs in all of them.
The purine analogue, 2- deoxycoformycin (DCF) has
been more successful in the treatment of this condition.
Matutes et al have reported partial or complete response
in 45% of their patients treated with this drug as a
single agent. [5] Recently Campath-1H, an anti- CD52
humanised monoclonal antibody, has been found to be
highly effective in T-PLL.[1,5,6,8] Responses have been
noted in approximately two thirds of patients including
those who have been refractory to treatment with
deoxycoformycin. An effective treatment schedule
recommended by Matutes is as follows:
Deoxycoformycin followed by Campath-1H in patients
who achieve partial response or are refractory to DCF.
Alternately Campath-1H may be used as the first line
therapy. [ 5] These strategies allow the harvesting of
peripheral blood stem cells and the use of high dose
chemotherapy with an autograft in young T-PLL
patients with the possibility of cure.

106

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