Eric Grignano

Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study

OBJECTIVE We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study. METHODS In this study, 123 patients with MDS and SIADs were analysed. RESULTS Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P < 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P < 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5). CONCLUSION The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent.

Inflammatory Arthritis in Patients With Myelodysplastic Syndromes: A Multicenter Retrospective Study and Literature Review of 68 Cases

AbstractWe describe the characteristics and outcome of inflammatory arthritis in patients with myelodysplastic syndrome (MDS) in a French multicenter retrospective study.Twenty-two patients with MDS (median age, 77.5 yr [interquartile range, 69–81]; 10 women) were included. Inflammatory arthritis presented as polyarthritis in 17 cases (77%) and with symmetric involvement in 15 cases (68%). At diagnosis, the median disease activity score 28 based on C-reactive protein (DAS28-CRP) was 4.5 [2–6.5]. Two patients had anti-citrullinated protein antibodies (ACPAs), and 1 had radiologic erosions. The median time between the diagnoses of arthritis and MDS was 10 months [6–42], with a median articular symptom duration of 3 months [2–8]. The diagnosis of both diseases was concomitant in 6 cases (27%); arthritis preceded MDS in 12 cases (55%), and occurred after MDS in 4 (18%). While the number of swollen and tender joints significantly decreased during follow-up, as did the median DAS28-CRP (from 4.3 [3.8–4.6] at baseline to 2.9 [1.75–3.3]; p < 0.05), CRP remained elevated (CRP >20 mg/L) in 8 patients (42%). Nevertheless, radiographic progression and new ACPA positivity were not observed during a median follow-up of 29 months [9–76]. While most of the patients were treated with steroids (n = 16) for arthritis, additional treatment was administered in only 4 patients (hydroxychloroquine, n = 2; sulfasalazine [Salazopyrin] and etanercept, n = 1, respectively). Eleven patients died during follow-up from acute myeloid leukemia (n = 5); infections (n = 3); or cerebral bleeding, cardiorespiratory failure, or undetermined cause (n = 1, respectively).Inflammatory arthritis associated with MDS can have various presentations and is often seronegative and nonerosive. Steroids alone are the most common treatment in MDS-associated arthritis, but that treatment is insufficient to control arthritis. Steroid-sparing strategies need to be identified.

Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

This retrospective study describes efficacy of Azacitidine on autoimmune disorders (AID) associated with MDS/CMML in 22 patients. Response of AID to Azacitidine was observed in 19 patients (86%). Reduction or discontinuation of steroids and/or immunosuppressive therapy (IST) was possible in 16 cases (73%). Hematologic response was seen in 55% of the patients. MDS/CMML and AID evolution was concordant in 13 cases (59%): both favorable (n=11), both unfavorable (n=2), but AID improved while MDS/CMML worsened (n=8) and vice versa (n=1). Azacitidine frequently seems effective in controlling steroid-dependent AID associated with MDS/CMML, but prospective studies are necessary to confirm those findings.

Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: A series of 26 cases and literature review

We wanted to describe the characteristics, treatment and outcome of autoimmune and inflammatory diseases (SAIDs) associated with chronic myelomonocytic leukemia (CMML), and conducted a French multicenter retrospective study and a literature review. We included 26 cases of CMML (median age 75 years, 54% female), 80% with CMML-1. CPSS score was low (0 or 1) in 75% of cases. SAIDS was systemic vasculitis in 54%. Diagnosis of the 2 diseases was concomitant in 31% cases, and CMML was diagnosed before SAIDs in 12 cases (46%). First line treatment for SAIDs consisted mostly of steroid, with 85% of response. Second-line treatment was needed in 40% cases. Six patients received hypomethylating agents, with 66% response on SAIDs. A literature review found 49 cases of CMML-associated SAIDs, in whom SAIDs was systemic vasculitis in 29% cases. Hence, vasculitis is the most frequent SAIDs associated with CMML. After initial response to steroids, recurrence and steroid-dependence were frequent. Hypomethylating agents may be interesting in this context.

Biologics in myelodysplastic syndrome-related systemic inflammatory and autoimmune diseases: French multicenter retrospective study of 29 patients.

BACKGROUND Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified. METHODS In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-α [TNF-α] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics. RESULTS We included 29 patients (median age 67years [interquartile range 62-76], 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis (n=6; 20%), relapsing polychondritis (n=8; 30%) and vasculitis (n=10; 34%). During a 3-year median follow-up (IQR 1.3-4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-α antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) (p<0.05). Rituximab had better response in vasculitis and TNF-α antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection. CONCLUSION This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising.

Autoimmune manifestations associated with lymphoma: characteristics and outcome in a multicenter retrospective cohort study

Abstract This French multicenter retrospective cohort study aimed to describe the autoimmune manifestations (AIMs) associated with lymphoma among patients hospitalized between 2005 and 2016 in three French University Hospitals. Among 2503 patients with lymphoma, 108 (4.3%) had AIMs, mostly autoimmune cytopenias (71.3%), neurological diseases (10.2%), kidney diseases (6.5%), systemic vasculitis (5.6%) and others. As compared with the 2395 lymphoma patients without AIMs, those with AIMs were older (p = .01), more frequently had B-cell chronic lymphocytic leukemia (p < .01) and less frequently diffuse large B-cell lymphomas (p = .01) and Hodgkin lymphoma (p = .01). The 5-year overall survival with lymphoma was 65% and 79% (p = .03) with and without AIMs. This large cohort study shows that various types of AIMs, mostly cytopenias, could be associated with lymphoma and affect the overall outcome with lymphoma, in particular for B-cell non-Hodgkin lymphoma (p = .01) and T-cell non-Hodgkin lymphoma (p = .01), with no survival difference noted for other types of lymphoma (p = .2).

Manifestations auto-immunes et inflammatoires des hémopathies lymphoïdes

In this literature review, we reported autoimmune and inflammatory disorders associated with lymphoid hematological malignancies, including non-Hodgkins lymphoma, Hodgkins lymphoma and chronic lymphocytic leukemia. The different types of systemic involvement are classified by affected organ. We listed in this review the joint diseases, skin, neurologic, hematologic, renal, and vasculitis. We tried to determine whether there is a correlation between each autoimmune manifestation and a specific type of lymphoma or a particular feature that may support a paraneoplastic origin, if there is an impact on the prognosis of the hematological malignancy, and finally, we identified the different therapeutic strategies used in the literature.

Autoimmune and inflammatory disorders associated with lymphoid hematological malignancies

In this literature review, we reported autoimmune and inflammatory disorders associated with lymphoid hematological malignancies, including non-Hodgkins lymphoma, Hodgkins lymphoma and chronic lymphocytic leukemia. The different types of systemic involvement are classified by affected organ. We listed in this review the joint diseases, skin, neurologic, hematologic, renal, and vasculitis. We tried to determine whether there is a correlation between each autoimmune manifestation and a specific type of lymphoma or a particular feature that may support a paraneoplastic origin, if there is an impact on the prognosis of the hematological malignancy, and finally, we identified the different therapeutic strategies used in the literature.

Autoimmune manifestations associated with myelodysplastic syndromes

Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with myelodysplastic syndromes (MDS). Available data suggest that ADs concern more often younger patients with higher risk IPSS. MDS subtypes associated with ADs are mainly MDS with single lineage dysplasia (MDS-SLD) and MDS with excess blasts (MDS-EB). Various types of ADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities as vasculitis, connective tissue diseases, inflammatory arthritis, and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can be seen. In general, ADs do not seem to confer worse survival, although certain ADs may be associated with adverse outcomes (i.e., vasculitis) or progression of MDS (Sweet syndrome). While steroids and immunosuppressive treatment (IST) remain the backbone of first-line treatment, increasing evidence suggests that MDS-specific therapy as hypomethylating agents, based on their immunomodulatory effect, may be effective in treating these complications and for sparing steroids.

Mise au pointManifestations auto-immunes et inflammatoires des hémopathies lymphoïdesAutoimmune and inflammatory disorders associated with lymphoid hematological malignancies

In this literature review, we reported autoimmune and inflammatory disorders associated with lymphoid hematological malignancies, including non-Hodgkins lymphoma, Hodgkins lymphoma and chronic lymphocytic leukemia. The different types of systemic involvement are classified by affected organ. We listed in this review the joint diseases, skin, neurologic, hematologic, renal, and vasculitis. We tried to determine whether there is a correlation between each autoimmune manifestation and a specific type of lymphoma or a particular feature that may support a paraneoplastic origin, if there is an impact on the prognosis of the hematological malignancy, and finally, we identified the different therapeutic strategies used in the literature.