Marta Lisa Battista

Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia

Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 x 10(9)/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m(2) rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count > or = 50 x 10(9)/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, -0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, -0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.

Lower dose rituximab is active in adults patients with idiopathic thrombocytopenic purpura

Rituximab 375 mg/m2 weekly for four weeks has significant activity in patients with immune thrombocytopenia. We evaluated the activity of lower dose rituximab (100 mg iv weekly for 4 weeks) in 28 adults with idiopathic thrombocytopenic purpura. Overall (platelet count > 50×109/L) and complete responses (platelet count > 100×109/L) were achieved in 21/28 (75%) and 12/28 (43%) patients respectively. The median time to response and time to complete response were 31 and 44 days respectively. After a median follow-up of 11 months (range 3–18), 7/21 (33%) patients relapsed and 3 needed further treatments. In patients with idiopathic thrombocytopenic purpura, lower dose rituximab seems to show similar activity to standard dose.

Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies

This prospective study investigated the efficacy, safety, and response duration of low-dose rituximab (100 mg fixed dose for 4 weekly infusions) together with a short course of steroids as first- or second-line therapy in 23 patients with primary autoimmune hemolytic anemia (AIHA). The overall response was 82.6% at month +2, and subsequently stabilized to ∼ 90% at months +6 and +12; the response was better in warm autoimmune hemolytic anemia (WAIHA; overall response, 100% at all time points) than in cold hemagglutinin disease (CHD; average, 60%); the relapse-free survival was 100% for WAIHA at +6 and +12 months versus 89% and 59% in CHD, respectively, and the estimated relapse-free survival at 2 years was 81% and 40% for the warm and cold forms, respectively. The risk of relapse was higher in CHD and in patients with a longer interval between diagnosis and enrollment. Steroid administration was reduced both as cumulative dose (∼ 50%) and duration compared with the patients past history. Treatment was well tolerated and no adverse events or infections were recorded; retreatment was also effective. The clinical response was correlated with amelioration biologic markers such as cytokine production (IFN-γ, IL-12, TNF-α, and IL-17), suggesting that low-dose rituximab exerts an immunomodulating activity. This study is registered at www.clinicaltrials.gov as NCT01345708.

Fludarabine plus cyclophosphamide and rituximab in waldenstrom macroglobulinemia: An effective but myelosuppressive regimen to be offered to patients with advanced disease

The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced promising results in chronic lymphocytic leukemia and other lymphoproliferative disorders. The authors report the final results from a multicenter, prospective study examining FCR in Waldenstrom macroglobulinemia (WM).

Rituximab therapy in adult patients with relapsed or refractory immune thrombocytopenic purpura: long-term follow-up results

Objective:  To evaluate the long‐term activity and toxicity profile of rituximab in adult patients with idiopathic immune thrombocytopenic purpura (ITP).

Low‐dose rituximab in adult patients with primary immune thrombocytopenia

Backgrounds: Rituximab 375 mg/m2 weekly for 4 wks has significant activity in adults with primary immune thrombocytopenia (ITP). In this setting, several evidences support the possible use of lower doses of rituximab. Objectives: To investigate the activity of low‐dose rituximab as salvage therapy in previously treated symptomatic ITP. Methods: Forty‐eight adult patients were treated prospectively with rituximab 100 mg weekly for 4 wks. Results: Overall and complete responses (CR) (platelet level ≥ 50 and 100 × 109/L) were 60.5% and 39.5%, respectively. In responders, the median time to response was 35 d (range: 7–112 d). The median time of observation was 18 months (range 3–49 months). Sixteen of 29 responding patients (55%) relapsed and 14 needed further treatments. The 12‐ and 24‐month cumulative relapse‐free survival was 61% and 45%, respectively. In univariate analysis, CR rate was in inverse relation with weight OR = 0.95, CI95% [0.91; 0.99] (P = 0.019) and age OR=0.96, CI95% [0.93; 0.99] (P = 0.047). Cox regression model showed that relapse probability increases as weight (HR = 1.06, CI95% [1.0031; 1.111]) and period between diagnosis and rituximab therapy (HR = 1.01, CI95% [1.002; 1.017]) increase. One patient developed an interstitial pneumonia 1 month after the end of rituximab treatment. No other infectious, hematologic or extra‐hematologic complications were documented during follow‐up. Conclusions: Low‐dose rituximab is active in ITP but has moderate long‐term effect. A comparative study with standard dose is warranted.

CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma.

Thirty untreated patients, median age 69 years (range 60 – 75 years), with diffuse large B-cell lymphoma (B-DLCL) were treated with a pegylated liposomal doxorubicin (PL-doxorubicin) modified CHOP-rituximab regimen. PL-doxorubicin 30 mg/m2, was given in combination with standard dosage of prednisone, vincristine, cyclophosphamide, rituximab (according to CHOP-R regimen) every 21 days for six courses. Cardiac toxicity was evaluated by mean of echocardiography for left ventricular ejection fraction (LVEF) evaluations and serum troponin-I levels. Overall response and complete response rates were 76% and 59%. Projected two year event free survival and overall survival are 65.5% and 68.5%. No treatment-related mortality was documented. WHO grade III-IV neutropenia and thrombocytopenia were 86% and 3%. Extra-hematological III-IV toxicity was represented, respectively, by a single case of infection, mucositis, and bleeding. LVEF evaluations and the troponin levels did not show significant changes over the course of the treatment. One patient with a previous history of atrial fibrillation experienced a single episode of arrhythmia. None of the patients developed palmar-plantar erythrodysesthesia. This regimen appears an active regimen for the treatment of elderly patients with B-DLCL. The replacement of conventional doxorubicin with PL-doxorubicin seems to be associated with a negligible incidence of extra-hematological toxicity, in particular cardiac and infectious complications.

Prognostic factors and outcome of Epstein–Barr virus DNAemia in high-risk recipients of allogeneic stem cell transplantation treated with preemptive rituximab

This study assessed incidence, predictive factors, and outcome of Epstein–Barr virus (EBV) DNAemia in 100 recipients of allogeneic hematopoietic stem cell transplant. A total of 68 patients received anti‐thymocyte globulin before unrelated grafts.

Clinical Presentation, Outcome and Risk Factors of Late-Onset Non- Infectious Pulmonary Complications After Allogeneic Stem Cell Transplantation

The term late-onset non-infectious pulmonary complications (LONIPCs) has been used to refer to events occurring later than 3 months after allogeneic hematopoietic stem transplant (HSCT), such as bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia, and lymphocytic or idiopathic interstitial pneumonia. The incidence of LONIPCs varies widely, ranging between 10% and 26%. Median time for LONIPC development is about 8-12 months after HSCT. Clinical symptoms may be insidious and non specific at the beginning and can be present in different types of infections. The diagnosis is made on the basis of thoracic high-resolution computed tomography and pulmonary function tests (PFT). It usually requires that standard cultures for infective agents on bronchoalveolar lavage are negative and is confirmed by transbronchial or lung biopsy, whenever possible. Total body irradiation and high doses of drugs used in the conditioning regimens, HLA disparity between donor and recipient, and chronic graft-versus-host disease (GVHD) are the main risk factors for LONIPCs. Since patients with LONIPCs have an increased risk of mortality because of infections or respiratory failure, pre- and post-transplant PFTs are strongly recommended in order to timely identify affected patients. The administration of antithymocyte globulin before unrelated donor transplants and slow taper of cyclosporine after transplant have been shown to prevent chronic GVHD and, therefore, the occurrence of LONIPCs.

EXTRACORPOREAL PHOTOPHERESIS (ECP) FOR TREATEMENT OF ACUTE AND CHRONIC GRAFT VERSUS HOST DISEASE: AN ITALIAN MULTICENTRIC RETROSPECTIVE ANALYSIS ON 94 PATIENTS ON BEHALF OF THE GRUPPO ITALIANO TRAPIANTO DI MIDOLLO OSSEO (GITMO)

Background Extracorporeal photopheresis (ECP) is considered a valid second-line treatment for acute and chronic graft versus host disease (GVHD). Methods Ninety-four patients with acute GVHD (aGVHD) (n = 45) and chronic GVHD (cGVHD) (n = 49), retrospectively recruited in 6 Italian centers, were submitted to ECP for second-line treatment. At the time of ECP, 22 (49%) and 23 (51%) of 45 patients with aGHVD were nonresponsive and in partial remission (PR) after steroids, respectively, and all the 49 patients with cGVHD were steroid refractory. Results Forty-one (91%) of 45 patients with aGVHD achieved complete remission (CR) after ECP. Fifteen (33%) of 45 patients developed cGVHD. The CR rate in patients who started ECP being nonresponsive and in PR after steroid was 86% and 96%, respectively. After a median follow-up of 20 months (range, 2-72), 15 (33%) of 45 patients developed cGHVD and 16 (35%) of 45 patients died, in 3 cases for aGVHD. A trend for a better survival was seen among patients who started ECP in PR after steroid (80% vs 50% at 2 years; P = 0.07). Overall, 22 (45%) of 49 patients and 17 (35%) of 49 patients with steroid refractory cGHVD achieved CR and PR after ECP, respectively. After a median follow-up of 27 months, 44 (90%) of 49 patients are alive, 21 of whom (48%) are on steroid. Conclusions Extracorporeal photopheresis is confirmed as an effective second-line treatment in both aGVHD and cGVHD, because it can induce a response in more than 80% of the patients and a long-term survival in at least 50% of the cases.