Bone marrow clearance of eosinophils, however, has not been achieved as often; however, it did not correspond to a clinical response (blood count, signs, and symptoms), and, therefore, its value is usually questionable. while on maintenance), and 6 were rechallenged with alemtuzumab. Five (83%) achieved second CHR after a median of 3.5 weeks, for a median duration of 123 weeks. Again, those given maintenance (n Bcl-2 Inhibitor = 3) had a longer time to progression than those who were only observed Cbll1 (= .04). Adverse effects were mostly related to infusion reactions and lymphopenia-related viral infections (despite antibiotic prophylaxis). One patient developed Epstein-Barr virusCrelated lymphoma. Conclusions Alemtuzumab is an effective treatment for patients with relapsed, refractory idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemiaCnot otherwise specified, in terms of both CHR achievement (even after repeated rechallenges) and duration (particularly if provided as Bcl-2 Inhibitor a maintenance therapy). Common adverse effects are related to infusion reactions and immunosuppression. and PDGFRgenes are highly sensitive to low-dose imatinib, 4C6 whereas immunosuppressive treatments are commonly effective long term for lymphocytic variant of hypereosinophilic syndrome. 7 CEL-NOS and I-HES are usually treated in the case of a symptomatic organ involvement, primarily with prednisone but also with hydroxyurea (HU), interferon alfa, and high-dose imatinib; bone marrow transplant (BMT) is the only curative option.8 Affected patients are Bcl-2 Inhibitor usually exposed to multiple different therapies over the disease course to counteract disease signs and symptoms.3 The largest published retrospective multicenter clinical analysis of therapy success (188 cases, including patients with I-HES, L-HES, and FIP1L1-PDGFR=.01) (Physique 1). Bone marrow was repeated in 8 patients: 3 normalized eosinophil percentage (complete remission), and 3 had more than 50% reduction in eosinophil percentage (partial remission). No cytogenetic response was observed in patients with CEL-NOS. Eleven (92%) patients relapsed; only one was on maintenance therapy at the time of relapse. One patient who has not relapsed yet (in CHR now for close to 300 weeks) has CEL-NOS with 12q-abnormality. Signs and symptoms at relapse were skin rash (4), fatigue (1), gastrointestinal tract symptoms (2), and renal failure due to eosinophilic infiltrate (1). Two (18%) patients died after relapse without further therapy. Three were given different therapies: BMT, cladribrine plus cytarabine followed by HU and BMT, HU followed by imatinib, respectively (1 died in complete remission of transplantation-related complications, and the other 2 are still alive). Open in a separate window Figure 1 Time to Progression in Patients Provided Maintenance Alemtuzumab vs. Observation Only Six were rechallenged with alemtuzumab, and 5 Bcl-2 Inhibitor (83%) achieved a second CHR after a median of 3.5 weeks (range, 1.9C5 weeks); 3 of the 5 patients were given maintenance therapy with alemtuzumab for a median of 2 weeks (range, 1C7 weeks). The median duration of the second CHR was 123 weeks (range, 5C240 weeks): those given maintenance (n = 3), although very short, again had longer TTP than the ones who were simply observed (n = 2; = .04). Of the 5 responders, 1 died while in CHR and one is in ongoing CHR for more than 240 Bcl-2 Inhibitor weeks. The remaining 3 relapsed (only 1 1 patient while still on therapy), 2 patients were rechallenged with alemtuzumab and are still alive and in CHR. Therapy-related adverse effects were seen in 10 (83%) patients: CMV reactivation (2), zoster reactivation (1), pneumonia (3), rash (1), Epstein-Barr virusCrelated diffuse large B cell lymphoma (1), fever (4), conjunctivitis (1), and moderate renal failure with creatinine 1.7 mg/dL (1). Among hematologic toxicities, lymphopenia was the only significant toxicity, seen in 11 of 12 patients. The intravenous route of administration was used in 8 patients, and the subcutaneous route was used in 4; no difference in treatment efficacy or observed toxicity was seen. Discussion In our series of patient with I-HES and CEL-NOS, alemtuzumab proved to be very effective in eliminating blood eosinophils and controlling disease-related signs and symptoms. The response is usually brisk (usually within a week) and, with maintenance therapy, can.