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Chapter 46 Autoimmune Hemolytic Anemia 659

TABLE Second-Line Treatment Options After Steroids
46.6
Treatment Dosing and Application Side Effects Precautions
Splenectomy (acute) Preferentially laparoscopic Infections, thrombosis Postoperative
thromboprophylaxis
Splenectomy (long term) — Infections Vaccination, patient
Venous thrombosis information
Rituximab 375 mg/m on days 1,8, 15, and 22 IV Infusional reactions Premedication with
2
Infections antihistamines (and
steroids)
Danazol 200–400/day PO Hepatotoxicity None
Cyclophosphamide PO or IV Neutropenia Neutrophil count monitoring,
Dose adjusted to neutrophil count Mutagenesis bladder protection after
high doses
Azathioprine 2.0–3.mg/kg/day PO Neutropenia Neutrophil count monitoring;
Dose adjusted to neutrophil count avoid interaction with other
drugs (e.g., allopurinol)
MFF 1–2 × 1 g/day PO Gastrointestinal
Cyclosporine PO Nephrotoxicity Monitoring of CyA levels and
Dose adjusted to blood levels of CyA Gum hyperplasia creatinine
Target level, 200–400 ng/mL
Alemtuzumab SC (variable doses) Neutropenia Antiinfectious prophylaxis
Complement inhibition with Infections Vaccination
eculizumab, TNT009
CyA, Cyclosporine A; IV, intravenous; MMF, mycophenolate mofetil; PO, oral; SC, subcutaneous.

basis of published data, no definite preference for one these treat- most serious, often fatal, but rare infectious complication is over-
ments is possible because of the insufficient quality of data. For both whelming pneumococcal septicemia. The risk of infections is highest
treatments, there have been no randomized studies comparing these shortly after splenectomy and decreases after 1 year. In a Scandinavian
two options. The decision for the preferred treatment in a specific population-based study, the adjusted relative risk of major infections
patient has therefore to be made on an individual basis based on (requiring hospital contact) in a matched indication comparison 1
judgment of the treating physician, the validity of available data on year after splenectomy for ITP (with a probably similar risk as AIHA)
short- and long-term efficacy, the assumed individual risk of adverse was 1.4. Although fatal postsplenectomy infections seem to be less
events, and the preference of the patient (Table 46.6). common in recent years, it is mandatory to take all measures to
reduce this risk. There is good but not definite evidence that preop-
Splenectomy erative vaccination reduces the risk of severe infections. Vaccination
For splenectomy, there are more, but older data on the short-term for pneumococci, meningococci, and Haemophilus influenzae should
efficacy, few data on long-term efficacy, and good recent data on be done before splenectomy. Pneumococcal vaccination should be
long-term adverse events. CR or PR is achieved in two-thirds of repeated regularly. Long-term antibiotic prophylaxis is probably not
patients (38% to 82%), depending on the percentage of secondary required in adults, but patients should be informed about this risk
cases. In addition, there is good evidence that a substantial number and should take antibiotics immediately in case unexplained fever.
of patients will remain in remission without the need for medical Risk in children may be reduced by subtotal splenectomy. The long-
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intervention for years. In the initial series by Chertkow and Dacie, term risk of venous thrombosis is moderate. Information for patients
only 2 out of 28 patients were in remission for more than 5 years, about short- and long-term risks is required and may be one of the
but 6 patients remained in a stable PR for up to 7 years. In 52 reasons for the fact that surgical treatment is underused. However,
splenectomized patients (percentage of primary AIHA unknown), splenectomy is the only therapy so far that may provide freedom from
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Coon found that 63% had a hematocrit of 30% or greater without treatment in a substantial number of patients for more than 2 years
steroids after a mean follow-up of 33 months, and 21% had a and possibly cure in about 20%.
hematocrit of 30% or greater with a prednisone requirement of
15 mg/day or less after a mean follow-up of 73 months. In a study Rituximab
38
by Allgood and Chaplin, 44% of patients were in CR after more Rituximab is currently the best available drug option for second-line
2
than 1 year after splenectomy. treatment. Given at a standard induction dose of 375 mg/m intra-
Splenectomy can safely be performed laparoscopically in almost venously on days 1, 8, 15, and 22. In a metaanalysis, the ORR for
all patients with primary AIHA with normal-sized spleens. With- WAIHAs after rituximab was 70% (67% for primary and 72% for
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drawal of steroids after splenectomy should be carried out slowly secondary). The CR rate was 42% (32% primary and 46% second-
(as described for primary treatment) to prevent hemolytic crises in ary). The CR rate was highest after 2–4 months. The rituximab
case of recurrence. The mortality rate of laparoscopic splenectomy schedule and dose are empirically derived from lymphoma treatment,
was 0.5% in a large national study. The main short-term risks and it is not known whether other schedules including maintenance
of splenectomy (in general) are infections, pulmonary embolism, are equal or better.
and splenic-portal thrombosis (rare in patients with a normal- There are limited data on short-term and almost no data on
sized spleen), but these risks have not been studied specifically in long-term efficacy and no data on long-term adverse effects. With
primary WAIHAs. regard to short-term efficacy, there seems to be not much difference
There is a lifelong increased risk of infections and of venous between rituximab and splenectomy. In one study, almost all patients
thrombosis and a very small risk of pulmonary hypertension. The (10 out of 11) had steroid-refractory primary WAIHAs, but four