Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study.

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.

Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia.

OBJECTIVES: To date no definitive cut-off value for cytomegalovirus (CMV) DNA load in bronchoalveolar lavage (BAL) fluid specimens has been established to discriminate between CMV pneumonia and pulmonary CMV DNA shedding in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. METHODS: The current retrospective study is aimed at assessing the range of CMV DNA loads quantified in BAL fluid specimens from allo-HSCT patients with pneumonia in which different microorganisms were causally involved. RESULTS: A total of 144 BAL specimens from 123 patients were included. CMV DNA was detected in 56 out of 144 BAL fluid specimens and the median CMV DNA load from patients in whom CMV pneumonia was unlikely or could be tentatively ruled out was 1210 (31-68, 920) IU/ml. The frequency of CMV DNA detection and median CMV DNA loads were comparable, irrespective of the attributable cause of pneumonia. Detection of CMV DNA loads in BAL fluid specimens >500 IU/ml was independently associated with pneumonia-attributable mortality. CONCLUSIONS: The current study highlights the difficulty in establishing universal CMV DNA load thresholds in BAL fluid specimens for distinguishing between CMV pneumonia and pulmonary CMV DNA shedding, and suggests that the presence of CMV DNA in BAL fluid specimens beyond a certain level may have a deleterious impact on patient outcome.

Community-acquired respiratory virus lower respiratory tract disease in allogeneic stem cell transplantation recipient: Risk factors and mortality from pulmonary virus-bacterial mixed infections.

Risk factors (RFs) and mortality data of community-acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co-infections in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo-HSCT recipients diagnosed of CARVs LRTD mono-infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co-infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono-infection (n = 19, group 5). Overall survival (OS) at day 60 after bronchoalveolar lavage (BAL) was significantly higher in group 1, 2, and 4 compared to group 3 (77%, 67%, and 73% vs 35%, respectively, P = .012). Recipients of group 5 showed a trend to better OS compared to those of group 3 (62% vs 35%, P = .1). Multivariate analyses showed bacterial co-infection as a RF for mortality (hazard ratio[HR] 2.65, 95% C.I. 1.2-6.9, P = .017). We identified other 3 RFs for mortality: lymphocyte count <0.5 × 109 /L (HR 2.6, 95% 1.1-6.2, P = .026), the occurrence of and CMV DNAemia requiring antiviral therapy (CMV-DNAemia-RAT) at the time of BAL (HR 2.32, 95% C.I. 1.1-4.9, P = .03), and the need of oxygen support (HR 8.3, 95% C.I. 2.9-35.3, P = .004). CARV LRTD co-infections are frequent and may have a negative effect in the outcome, in particular in the context of bacterial co-infections.

Primary cutaneous marginal IgG4 lymphoma and Rosai-Dorfman's disease coexisting in several lesions of the same patient.

We report the unique association of primary cutaneous marginal zone B-cell lymphoma and Rosai-Dorfman disease (RDD)-type histiocytic infiltrates involving the same lesions. The patient was an 82-year-old woman with 3 long-standing, well-circumscribed firm erythematous to brownish plaques on her left arm, right scapular area, and lumbosacral area. Histopathologic examination disclosed a dermal and subcutaneous nodular lymphoplasmacytic infiltrate with evidence of germinal center colonization and light-chain restriction and sheets of S-100 CD68-positive histiocytes with ample pale cytoplasm and occasional emperipolesis of lymphocytes. The neoplastic plasma cells expressed immunoglobulin (Ig) G4. A review of 14 examples of cutaneous RDD showed a substantial number of IgG4-positive cells in only 3 of them, and a review of 8 primary cutaneous marginal zone B-cell lymphomas disclosed only 2 with significant IgG4 expression. The coexistence of lymphomas and RDD has been rarely reported in the literature but only seldom involving the same lymph node and-to the best of our knowledge-never in the skin.