Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

Characteristics of chemotherapy-induced diabetes mellitus in acute lymphoblastic leukemia patients.

Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and ß cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).

Clinical features and treatment of 7 Chinese TAFRO syndromes from 96 de novo Castleman diseases: a 10-year retrospective study.

BACKGROUND: Castleman disease (CD) is a rare polyclonal lymphoproliferative disorder with unknown etiology. TAFRO syndrome is now regarded as a specific subtype of CD, and is still a huge challenge for clinicians. METHODS: To clarify the clinical features and management of TAFRO syndrome in China, we retrospectively analyzed 96 patients with HIV-negative CD (52 with unicentric CD and 44 with multicentric CD), who were diagnosed and treated at our center between 2008 and 2017. Specially, we systematically reviewed the 7 TAFRO syndrome cases based on the 2015 criteria proposed by Masaki. RESULTS: Among the 7 cases, there were 3 men and 4 women, and the median age was 53 years. The main symptoms included thrombocytopenia (7/7), anasarca (7/7), fever (4/7), renal dysfunction (7/7), and organomegaly (6/7). One patient was treated with corticosteroid monotherapy, one received RD (Rituximab, dexamethasone), and 5 received CHOP/COP like chemotherapy as first-line treatment, 2 of the 5 combined with Rituximab. Four patients needed hemodialysis or CRRT because of progressive renal failure. The outcome for TAFRO syndrome was significantly worse compared to other types of CD. Although 3 patients improved after early treatment, 4 patients died due to disease progression, and only one patient achieved complete resolution of all the symptoms after changing to lenalidomide based regimen. CONCLUSIONS: This study reveals that TAFRO syndrome is more severe and has more systemic symptoms than other iMCD, most cases need active treatment, and their prognoses are poor. Lenalidomide based regimen may be as a promising new therapy for TAFRO syndrome.