A Case of Pure Red Cell Aplasia Associated with Angioimmunoblastic T-cell Lymphoma

Article (PDF Available)inCancer Research and Treatment 42(2):115-7 · June 2010with22 Reads
DOI: 10.4143/crt.2010.42.2.115 · Source: PubMed
Abstract
Pure red cell aplasia is a bone marrow failure characterized by a progressive normocytic anemia and reticulocytopenia without leucopenia and thrombocytopenia. It is associated with various hematologic diseases. However, pure red cell aplasia with angioimmunoblastic T cell lymphoma has rarely been reported. Here we describe a 43-year-old woman with pure red cell aplasia associated with angioimmunoblastic T-cell lymphoma. She had severe anemia (hemoglobin 6.9 g/dL) and a low reticulocyte count (0.2%). Direct and indirect Coombs' tests were positive. A CT scan of the abdomen revealed marked hepatosplenomegaly and small multiple lymphadenopathies. A bone marrow biopsy revealed focal infiltration of abnormal lymphoid cells and absence of red cell precursors. Splenic biopsy was compatible with angioimmunoblastic T-cell lymphoma. Ultimately, diagnosis of pure red cell aplasia associated with angioimmunoblastic T-cell lymphoma was made. After initiating CHOP therapy, the patient achieved complete remission, which was accompanied, shortly thereafter, by a rise in hemoglobin levels which finally returned to normal.
VOLUME 42 NUMBER 2 JUNE 2010
115
A Case of Pure Red Cell Aplasia Associated with
Angioimmunoblastic T-cell Lymphoma
Introduction
Pure red cell aplasia is a bone marrow failure characterized by a
progressive normocytic anemia and reticulocytopenia without
leucopenia and thrombocytopenia. It is associated with various
diseases such as thymoma, lympho- and myelo-proliferative
disorders, autoimmune diseases, infection, and drugs (1). Although
various types of lymphoma may also be associated with this
condition, the case of a pure red cell aplasia with angioimmunoblastic
T cell lymphoma (AITL) has rarely been reported (2-6). We now
describe a case of pure red cell aplasia associated with AITL. It was
successfully treated with the aid of combination chemotherapy.
Case Report
A 43-year-old woman presented with malaise and fatigue that had
developed one month prior. She was mentally retarded but was in
good health until the symptoms developed. A CBC performed in a
private clinic showed a hemoglobin level of 4.2 g/dL, a white blood
cell count of 3,000/μL, and a platelet count of 234,000/μL. After a
packed red cell transfusion, she was transferred to our hospital for
further evaluation and treatment.
She had no signs of fever, weight loss, or night sweats. Laboratory
finding at admission showed a hemoglobin level of 6.9 g/dL (MCV
84.9 fL), a white blood cell count of 3,900/μL, a platelet count of
197,000/μL, a reticulocyte count of 0.2%, serum ferritin of 814.8 μg/L,
LDH of 664 U/L, total protein of 6.1 g/dL, albumin of 3.9 g/dL, and
normal liver and kidney function tests. A peripheral blood smear
revealed normocytic normochromic anemia. Direct and indirect
Coombs’ tests were indicative of strong positivity (4+). ANA was
skeleton level 3, and C4 was decreased. A serologic test for EBV
revealed that the patient was negative for EBV IgM and positive for
EBV IgG. PCR for parvovirus B19 was negative. A CT scan of the
abdomen revealed marked hepatosplenomegaly and small multiple
lymphadenopathies in the aortocaval, para-aortic, and retrocaval areas.
A PET-CT showed mild FDG uptake in the bilateral axillary,
aortocaval, para-aortic, and retrocaval lymph nodes with hepato-
Cancer Res Treat. 2010;42(2):115-117
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Pure red cell aplasia is a bone marrow failure characterized by a progressive normocytic
anemia and reticulocytopenia without leucopenia and thrombocytopenia. It is associated
with various hematologic diseases. However, pure red cell aplasia with angioimmunoblastic
T cell lymphoma has rarely been reported. Here we describe a 43-year-old woman with pure
red cell aplasia associated with angioimmunoblastic T-cell lymphoma. She had severe
anemia (hemoglobin 6.9 g/dL) and a low reticulocyte count (0.2%). Direct and indirect
Coombstests were positive. A CT scan of the abdomen revealed marked hepatospleno-
megaly and small multiple lymphadenopathies. A bone marrow biopsy revealed focal
infiltration of abnormal lymphoid cells and absence of red cell precursors. Splenic biopsy
was compatible with angioimmunoblastic T-cell lymphoma. Ultimately, diagnosis of pure red
cell aplasia associated with angioimmunoblastic T-cell lymphoma was made. After initiating
CHOP therapy, the patient achieved complete remission, which was accompanied, shortly
thereafter, by a rise in hemoglobin levels which finally returned to normal.
Key words
Red-cell aplasia, Pure, Lymphoma, T-cell
Jung-Hye Choi, M.D.,Ph.D.1
Young-Ha Oh, M.D.,Ph.D.2
Ile-Kyu Park , M.D.,Ph.D.3
Departments of
1
Internal Medicine,
2
Pathology, and
3
Laboratory Medicine,
Hanyang University College of Medicine,
Seoul, Korea
Correspondence: Jung-Hye Choi, M.D., Ph.D.
Department of Internal Medicine, Hanyang
University Guri Hospital, 249-1, Gyomoon-dong,
Guri 471-701, Korea
Tel: 82-31-560-2236
Fax: 82-31-553-7369
E-mail: jhcmd@hanyang.ac.kr
Received October 18, 2009
Accepted December 5, 2009
DOI 10.4143/crt.2010.42.2.115
Case Report
splenomegaly and diffuse bone marrow involvement. A bone marrow
biopsy revealed one lymphoid follicle, focal infiltration of abnormal
lymphoid cells and the absence of red cell precursors (Fig. 1A). The
infiltrated lymphoid cells were mostly positive for CD3. A
chromosomal study showed 46, XX. These finding are consistent
with a pure red cell aplasia with lymphoma involvement. A splenic
biopsy showed diffuse infiltration of lymphoplasma cells admixed
with congested vascular spaces. There were multifocal and
perivascular aggregations of atypical lymphoid cells with clear
cytoplasm, which were positive for CD3 (Fig. 1B). Despite the fact
that there was not enough tissue biopsied to achieve a diagnosis, it was
considered to be AITL. In accordance with the clinical manifestations,
results of laboratory tests, and bone marrow and splenic biopsies, we
finally diagnosed the patient as having a pure red cell aplasia
associated with AITL (stage IVA).
During diagnostic work-up, she developed fever, jaundice,
hematuria, and skin rash on her whole body. Her hemoglobin rapidly
decreased from 6.1 to 3.7 g/dL. Laboratory tests at that time were
consistent with hemolytic anemia. She was treated with a washed
RBC transfusion and prednisone but there was no response. The
patient was started on CHOP (cyclophosphamide, adriamycin,
vincristine, prednisone) chemotherapy. After one cycle, hemoglobin
levels increased to 9.7 g/dL and all of the above noted symptoms
disappeared. A bone marrow biopsy after one cycle of CHOP showed
hypercellular marrow with erythroid hyperplasia. Fig. 2 describes
change in hemoglobin levels during treatment. After 6 cycles of
CHOP therapy, she achieved complete remission and a normal
hemoglobin level and remained so out to 20 months.
Discussion
AITL is an aggressive mature T cell lymphoma. AITL patients
present with systemic symptoms characterized by fever, skin rash,
generalized lymphadenopathy, and hepatosplenomegaly. In addition,
AITL has frequently been accompanied by various immunologic and
hematologic diseases such as autoimmune hemolytic anemia,
vasculitis, rheumatoid arthritis, and autoimmune thyroid disease (7).
However, AITL associated with pure red cell aplasia is very rare.
A MEDLINE search of the National Library of Medicine database
(English literature only) yielded 8 additional cases of pure red cell
aplasia associated with AITL. The main clinical findings of these
patients are noted in Table 1. There were 6 male and 2 female
patients, with a median age of 71 years (range: 4679). The median
hemoglobin level was 7.6 g/dL. All patients who had available labo-
ratory data (7 patients) showed a positive direct Coombs’ test. Bone
marrow involvement in AITL was observed in 4 patients (50%).
Although all patients were treated with corticosteroids, combination
Cancer Res Treat. 2010;42(2):115-117
116
CANCER RESEARCH AND TREATMENT
Fig. 2. Change of hemoglobin levels during treatment.
Fig. 1. (A) Bone marrow biopsy shows focal infiltration of abnormal lymphoid cells and the absence of red cell precursors (H&E, ×400). (B)
Splenic biopsy shows diffuse infiltration of atypical lymphoid cells which are positive for CD3 (CD3, ×400).
chemotherapy, and/or plasmapheresis, treatment outcomes were
dismal. Five patients died of disease progression, infection, or pulmo-
nary embolism. Corticosteroid and plasmapheresis resulted in only
transient improvement. However, two patients who received combi-
nation chemotherapy achieved a complete response. In our case,
prednisone alone did not improve the patient's hemoglobin level or
reduce her systemic symptoms. However, after the 1
st
round of CHOP
chemotherapy, hemoglobin levels increased and all of her previous
symptoms disappeared. After 6 cycles of CHOP, she was in complete
remission with a normal hemoglobin level. Therefore, aggressive
combination chemotherapy should be used in pure red cell aplasia
associated with AITL.
The pathogenesis of pure red cell aplasia associated with AITL has
not been elucidated yet. Lynch et al. described significant inhibition of
CFU-E cultures and modest inhibition of the BFU-E, but no inhibition
of the CFU-GM from normal bone marrow using patient's serum (2).
And a dose-dependent inhibitor of CFU-E was present in the serum of
the patient (2). Other reports also demonstrated that the patient's serum
before treatment significantly inhibited BFU-E formation but not
CFU-GM from normal CD34+ progenitor cells (3). These results
suggested that humoral factors causing inhibition of red cell pre-
cursors might play an important role in the pathogenesis of pure red
cell aplasia associated with AITL.
The histological diagnosis of AITL is difficult and sometimes it has
been misdiagnosed as other hematological or infectious diseases. In
particular, the histological appearance of extranodal involvement such
as bone marrow, spleen, skin and lung are usually nonspecific. In our
case, we could obtain tissues from bone marrow and spleen but not
lymph nodes because lymphadenopathies were existed only intra-
abdominal area. Although our patient did not express CD10 and
EBV-LMP1, histological features and clinical findings were con-
sistent with AITL.
In summary, pure red cell aplasia with AITL is a very rare con-
dition and may be associated with an immune disorder. Although it
has an aggressive clinical course and poor long-term outcome, the cli-
nician must try to treat it with aggressive combination chemotherapy.
Further investigation regarding the pathogenesis of and novel thera-
peutic approach to this rare condition, such as new immunomodula-
tory strategies, are needed to determine the optimal therapy of pure
red cell aplasia with AITL.
Jung-Hye Choi, et al_Pure Red Cell Aplasia Associated with AITL
VOLUME 42 NUMBER 2 JUNE 2010
117
Case Age/ Hb Reti WBC Platelets Direct BM
No. Sex (g/dL) (%) (×10
9
/L) (×10
9
/L) coombs invasion Treatment Reference
1 73/M 7.3 0 10.6 206 + -Corticosteroid 2
2 54/M 6.9 0.1 1.8 200 + + Prednisone, cytoxan, plasmapheresis 2
3 71/F 8.6 0 9.2 307 + + Prednisone, combination chemotherapy, plasmapheresis 2
4 46/M 7.8 0 3.6 112 + Chemotherapy 3
5 71/M 6.6 0 3.9 33 + -Combination chemotherapy 4
6 61/M 8.2 0 4.0 50 + -Combination chemotherapy 4
7 77/M 8.2 0.04 12.4 140 + -Plasmapheresis, prednisone 5
8 79/ F 6.5 1 18.0 149 + + Prednisone 6
Table 1. Clinical findings in patients with angioimmunoblastic T cell lymphoma and pure red cell aplasia
1. Djaldetti M, Blay A, Bergman M, Salman H, Bessler H. Pure red cell aplasia--a rare
disease with multiple causes. Biomed Pharmacother. 2003;57:326-32.
2. Lynch JW, Elfenbein GJ, Noyes WD, Braylan RC, Gross MA, Weiner RS. Pure red cell
aplasia associated with angioimmunoblastic lymphadenopathy with dysproteinemia.
Am J Hematol. 1994;46:72-8.
3. Tsujimura H, Sakai C, Takagi T. Pure red cell aplasia complicated by angioimmuno-
blastic T-cell lymphoma: humoral factor plays a main role in the inhibition of
erythropoiesis from CD34 (+) progenitor cells. Am J Hematol. 1999;62:259-60.
4. Higuchi T, Mori H, Niikura H, Omine M. Hypocomplementemia and hematological
abnormalities in immunoblastic lymphadenopathy and immunoblastic lymphadenopathy-
like T cell lymphoma. Acta Haematol. 1996;96:68-72.
5. Alberti E, Aldovini D, Mazzon C, Dal Rì P, Rubertelli M. Angioimmunoblastic
Lymphadenopathy with Dysproteinemia. Report of a case with pure red cell aplasia.
Haematologica. 1982;67:919-25.
6. Al Hilali M, Joyner MV. Pure red-cell aplasia secondary to angioimmunoblastic
lymphadenopathy. J R Soc Med. 1983;76:894-5.
7. Dogan A, Attygalle AD, Kyriakou C. Angioimmunoblastic T-cell lymphoma. Br J
Haematol. 2003;121:681-91.
References
    • "After an analysis of AIHA or Evans' syndrome, encountered in patients with NHL, it has been reported that warm antibody-mediated AIHA is more frequent in B-cell lymphomas, while cold antibody-mediated AIHA mainly occurs in T-cell lymphomas [26]. Additionally, in all cases of AITL associated with PRCA, positive Coombs test has been noted [12]. Coexistence of AIHA and PRCA in malignant lymphoma has also been reported [8]. "
    [Show abstract] [Hide abstract] ABSTRACT: Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocytopenia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma (NHL). The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders.
    Full-text · Article · Apr 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocyto-penia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma (NHL). The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders.
    Full-text · Article · Apr 2012 · The Scientific World Journal
  • [Show abstract] [Hide abstract] ABSTRACT: Angioimmunoblastic T-cell lymphoma (AITL) is a unique type of peripheral T-cell lymphoma with a constellation of clinical symptoms and signs, including weight loss, fever, chills, anemia, skin rash, hepatosplenomegaly, lymphadenopathy, thrombocytopenia and polyclonal hypergammaglobulinemia. The histological features of AITL are also distinctive. Pure red cell aplasia is a bone marrow failure characterized by progressive normocytic anemia and reticulocytopenia without leucopenia or thrombocytopenia. However, AITL with abdominal pain and pure red cell aplasia has rarely been reported. Here, we report a rare case of AITL-associated pure red cell aplasia with abdominal pain. The diagnosis was verified by a biopsy of the enlarged abdominal lymph nodes with immunohistochemical staining.
    Article · Aug 2013
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