Case history
A 70-year-old woman, followed at our institution for CMML associated
with wAIHA, was admitted at hospital for dyspnea and malaise in March
2017. At the time of CMML diagnosis 15 years earlier, in 2002, she
presented with splenomegaly, oral lichen planus and IgG-mediated wAIHA.
At that time, bone marrow examination did not show excess of blasts and
karyotype was normal. CMML did not require any treatment by itself but
treatment for symptomatic anemia was initiated. AIHA responded initially
to prednisone (1 mg/kg/day) but relapses were frequent during tapering
and the patient experienced many steroids complications. Mycophenolic
acid failed to control the hemoglobin level and the patient required
repeated packed red blood cells (PRBC) transfusions. A splenectomy was
performed in 2007, leading to a prolonged control of AIHA. The
hemoglobin level remained stable between 100 and 110 g/L until 2015,
although haptoglobin level was repeatedly below the normal range, and
then it gradually decreased. In the meantime, hydroxyurea had been
initiated in June 2008, because of increasing leukocytosis. Treatment
with recombinant erythropoietin was initiated in November 2016, because
anemia was thought to be more related to bone marrow failure than
hemolysis at that time. Erythropoietin was ineffective as well as
prednisone which was resumed at the beginning of 2017. The patient
received several RBCP transfusions, especially after hip prosthesis for
intercurrent femoral neck fracture, but their efficacy was very
transient. Thrombocytopenia then developed for the first time in the
history of the disease. At admission in March 2017, hemoglobin level was
63 g/L with reticulocytes count 227 G/L, platelet count was 61 G/L and
white blood cells were 23 G/L with 22% monocytes and 15% myelocytes
and metamyelocytes. There were both elevation of LDH level (1.5 x UNV)
and decreased haptoglobin level (< 0.10 g/L). Direct
antiglobulin test (DAT) was positive for IgG (strong) and C3d (low).
Bone marrow aspiration showed both erythroblastic and monocytic
hyperplasia without blast excess, thus eliminating leukemic
transformation. The megakaryocytes were normally present, suggesting
that thrombocytopenia was related to peripheral destruction of
platelets. Screen for cold agglutinins and a paroxysmal nocturnal
hemoglobinuria (PNH) clone was negative. The diagnosis of Evans syndrome
was established. The dose of prednisone was increased to 2 mg/kg/day and
the patient then received, within a short period of time, daily boluses
of high-dose methylprednisolone (500 mg/day for three days), intravenous
immunoglobulins (1 g/kg/day for two consecutive days) and four infusions
of rituximab (375 mg/m² weekly). All these treatments failed and several
plasma exchanges were performed, due to poor anemia tolerance with a
hemoglobin level of 31 g/L at nadir. Despite all these procedures,
hemoglobin level did not improve nor stabilize. About one month after
the last infusion of rituximab, a treatment with eculizumab was started.
The patient received 600 mg of eculizumab every week for four weeks and
then 900 mg every two weeks. After starting eculizumab, hemoglobin and
platelet levels gradually increased. Three months later, hemoglobin has
stabilized around 10 g/L, while the platelet and LDH levels were
normalized (table 1). For the first time in her medical story, the
haptoglobin level went back to near normal values. The infusions of
eculizumab were progressively spaced out and then definitively stopped
in July 2018, after 14 months of treatment. With a follow-up of 12
additional months, no recurrence of AIHA has occurred.