Sir,
Richter's transformation (RT) is a rare dreaded complication in patients with chronic
lymphocytic leukemia (CLL). The most common histology in RT is diffuse large B-cell
lymphoma (DLBCL); other lymphomas such as Hodgkin disease, hairy cell lymphoma, and
T-cell lymphoma are very scarcely reported. We report a case of Hodgkin variant of
RT in CLL patient successfully treated with adriamycin, bleomycin, vinblastine, and
dacarbazine (ABVD) and on follow-up for 5 years.
A 32-year-old male patient referred to our hospital in July 2008 with symptoms of
fatigue and generalized lymphadenopathy. Clinical examination revealed Eastern Cooperative
Oncology Group performance status 1 and mild pallor, generalized lymphadenopathy.
His hemogram showed hemoglobin – 10.5 g/dL, total leukocyte count – 40 × 109/L, and platelet counts – 150 × 109/L. Peripheral blood smear examination showed normochromic normocytic anemia with
80% lymphoid cell. Flow cytometric analysis of peripheral blood revealed 80% CD19+,
CD5+ abnormal lymphoid cell, which are positive of CD20 and CD23 and negative for
FMC7 and CD3. Renal and liver functions were within the normal limit. Direct Coombs
test was negative, and there are no features of hemolysis. Diagnosis of CLL Rai Stage
III was made, and the patient was started fludarabine d1-3 (25 mg/m2) and cyclophosphamide d1-3 (250 mg/m2) each over 28 days. After six cycles, the disease was in complete remission. After
a period of 4-year follow-up, he developed progressive cervical lymphadenopathy and
B symptoms, and imaging revealed supra- and infra-diaphragmatic disease. Histopathological
examination of the cervical lymph node revealed Reed–Sternberg cells with typical
morphology and immunophenotype (CD30+, Epstein–Barr virus [EBV] latent membrane protein-1
[LMP-1]+, CD3−, CD20−, and CD15−) associated with the characteristic polymorphous
inflammatory background [Figure 1]. The final diagnosis, Hodgkin variant of RT Stage III, was made. He achieved complete
remission after six cycles of ABVD. Given the lack of data for autologous stem cell
transplantation (ASCT) and after discussing with the patient, we decided to observe
him. The patient continues to be in complete remission after 5 years of RT.
Figure 1: (a and b) Microphotograph shows effacement of architecture by polymorphous
population of cells comprising eosinophils, histiocyte, and large mononuclear cell
([a] H and E, ×100, [b] H and E, ×200). The large cells are immunopositive for CD30
([c] ×200), Epstein–Barr virus latent membrane protein-1 ([d] ×200) while negative
for CD20 ([e] ×200) and CD15 ([f] ×200)
The incidence and median time for the development of Hodgkin variant of RT in CLL
patient is 0.1% to 0.5% and 2.6–6 years, respectively.[1]
[2] Hodgkin variant can be clonally related or unrelated to CLL with longer survival
seen in later cases.[3] In our report, Hodgkin cells are clonally independent. The presence of EBV LMP-positive
Reed–Sternberg cells supplements the hypothesis that marked prolonged immunosuppression
in CLL (particularly with fludarabine therapy) leads to EBV-related B-cell proliferation
with subsequent development of lymphoma-like hyperleukocytosis (HL). ABVD, mustargen,
oncovin, procarbazine, and prednisone, and cyclophosphamide, oncovin, procarbazine,
and prednisone regimens have been used in such cases with limited outcome. Prognosis
is poor than de novo HL but better than DLBCL transformation of CLL. Median overall survival in largest
series of Hodgkin variant of RT was only 8 months with few long-term survivors.[3] The role of high-dose chemotherapy with ASCT and the subset of patients who benefit
from it are not well defined in Hodgkin variant of RT unlike DLBCL variant. We described
the good response with ABVD therapy, reserving the ASCT at the time of progression
if needed. In conclusion, our case highlights that Hodgkin variant of CLL can have
heterogeneous course and not all patients may require transplant in this variant.
ABVD can be considered as a reasonable option with good outcome. More insights into
predictive and prognostic factors are required to select patients who will benefit
from high-dose chemotherapy with ASCT.
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