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Blood, 1 February 2002, Vol. 99, No. 3, pp. 1096-1097
CORRESPONDENCE
To the editor:
Sustained response of refractory chronic lymphocytic leukemia
in progression complicated by acute hemolitic anemia to anti-CD20
monoclonal antibody
We have read with interest the paper of Huhn et al on
rituximab therapy of patients with B-cell chronic lymphocytic leukemia (CLL).1 Seven of 28 heavily pretreated patients showed a
partial remission (NCI criteria), lasting for a median of 20 weeks.
Huhn et al conclude that rituximab as a single agent might play a role in patients with poor marrow reserve for whom other options have failed. We would like to comment on the role of this therapy in refractory patients with concomitant acute hemolitic anemia (AHA). About 4% of CLL patients develop AHA,2 mainly in those
with active disease, and few data exist regarding the efficacy and safety of rituximab in this clinical setting.3 We recently employed rituximab as rescue therapy for a patient
with resistant B-cell chronic lymphocytic leukemia (B-CLL) and
secondary AHA. A 52-year-old patient, diagnosed in January 1996 as
having stage Rai II classical B-CLL, was admitted to our department
after 24 months in disease progression (huge splenomegaly, anemia, and
lymphocyte count above 50 000/µL) complicated by AHA (warm
antibody type). Thereafter, he was given the following therapy: chlorambucil and prednisone, fludarabine+mitoxantrone+dexamethasone (FND), and cyclophosphamide+adriamycin+vincristine+prednisone (CHOP). After each line of therapy the patient attained only a short
(less than 6 months') partial remission (PR), followed by tumor
regrowth (splenomegaly, lymphocytosis, and anemia). In August 2000 he
was admitted to our department again for disease progression. Physical
examination revealed overt jaundice and hepato- and splenomegaly (15 cm
below costal margin). Laboratory data were as follows: hematocrit, 21.3%; hemoglobin level, 6.6 g/dL; reticulocyte
count, 320 × 109/L; mean corpuscular volume, 106 fL; platelet count, 166 × 109/L; white blood cell
count, 32 × 109/L with 38% lymphocytes,
50% prolymphocytes, and 12% neutrophils; bilirubin level, 35 µM;
lactate dehydrogenase level, 894 IU/L (normal is below 460 IU/L); and a
direct antiglobulin test (DAT) positive for both complement (3+/4+) and
IgG (4+/4+). The immunophenotype of peripheral blood lymphoid cells
showed a typical B-CLL pattern (CD19+/CD5+/CD23+/CD10 )
with unusual CD20 bright fluorescence intensity. He was naïve for hepatitis viruses and had an antibody pattern indicating a remote
infection of Epstein Barr virus and cytomegalovirus. The patient did
not respond to a 10-day course of 6-metilprednisolone IV (250 mg/d).
Then, after obtaining the informed consent, we began a therapy with
rituximab (Mabthera) at 375mg/m2/wk for 4 weeks,
and tapered prednisone over 2 weeks. The follow-up is shown in Figure
1.
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| Figure 1.
Changes in hemoglobin level, lymphocyte count, and DAT score following
rituximab therapy.
The solid black rectangle indicates prednisone therapy; the vertical
arrows, rituximab therapy; and DAT, direct antiglobulin test.
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The first infusion of rituximab produced a marked reduction of the
lymphocytosis, and after 5 days the hemoglobin level started to
increase. No side effects related to rituximab infusion were recorded.
At the end of week 8, the patient was re-evaluated. There were no signs
of active AHA (reticulocyte count and hemoglobin, lactate
dehydrogenase, and haptoglobin levels within range), and DAT
was slightly positive (score +/4+). According to NCI criteria, the
patient was judged to be in PR, because of the persistence of the
splenomegaly, while having normal hemogram elements and a bone
marrow interstitial lymphocyte infiltration of about 15%. After 12 months of follow-up the patient is still in PR, and this compares
favorably to the median disease progression time of 20 weeks reported
by Huhn et al.1 The rapid response of AHA to rituximab
markedly contrasts to the slow response to conventional therapy
(median, 4.5 months), as reported by Mauro et al.2 The
almost simultaneous response of CLL and AHA could be
interpreted as due to the clearance of both the neoplastic and the
autoreactive clones.3 Further studies are warranted to
clarify the anti-CD20 role in the treatment of CLL in general and in
patients with secondary AHA in particular.
Emilio Iannitto, Emanuele Ammatuna, Carla Marino, Sonia Cirrincione, Gioacchino Greco, and Gugcielmo Mariani
Correspondence: Emilio Iannitto, Haematology and Bone Marrow
Transplantation Unit, University of Palermo, via del Vespro 129, 90127 Palermo, Italy; e-mail: eiannitto{at}tin.it
References
1.
Huhn D, von Shilling A, Wilhelm M, et al.
Rituximab therapy of patients with B-cell chronic lymphocytic leukemia.
Blood.
2001;98:1326-1331[Abstract/Free Full Text].
2.
Mauro FR, Foà R, Cerretti R, et al.
Autoimmune hemolitic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features.
Blood.
2000;95:2786-2792[Abstract/Free Full Text].
3.
Seipelt G, Bohme A, Koschmider S, Hoelzer D.
Effective treatment with rituximab in a patient with refractory prolymhocytoid transformed B-chronic lymphocytic leukemia and Evans syndrome.
Ann Hematol.
2001;80:170-173[CrossRef][Medline]
[Order article via Infotrieve].
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