Incidence, characteristics, management and outcome of patients with follicular lymphoma with tumor epidural compression, a study on 22 cases.

PURPOSE: Follicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression. MATERIAL AND METHODS: Observational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000-2021). RESULTS: Between 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range=[1-216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47-90%) of patients. The median PFS was of 36 months (95% CI 24-NA) and 5 years OS estimate was 79% (95% CI 62-100%). Two patients developed a relapse at a second epidural site. CONCLUSION: FL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.

Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study.

Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in Myeloid Neoplams (MNs) exhibit DNA hypermethylation via 2-hydroxyglutarate (2HG) over-production. Clinical impact of azacitidine (AZA) remains inconsistent in IDH1/2-mutated MNs and the potential of serum 2HG as a suitable marker of response to AZA is unknown. To address these questions, we retrospectively analyzed 93 MNs patients (78 AML, 11 MDS, 4 CMML) with IDH1/2 mutations treated with AZA. After a median of 5 cycles of AZA, overall response rate was 28% (including 15% complete remission) and median OS was 12.3 months (significantly shorter in AML compared to MDS/CMML patients). In multivariate analysis of AML patients, DNMT3A mutation was associated with shorter OS while IDH1/2 mutation subtypes had no independent impact. No difference was observed in serum 2HG levels upon AZA treatment between responding and refractory patients suggesting that serum 2HG cannot be used as a surrogate marker of AZA response.

Developing a patient decision aid for the treatment of women with early stage breast cancer: the struggle between simplicity and complexity.

BACKGROUND: A patient decision aid (PtDA) can support shared decision making (SDM) in preference-sensitive care, with more than one clinically applicable treatment option. The development of a PtDA is a complex process, involving several steps, such as designing, developing and testing the draft with all the stakeholders, known as alpha testing. This is followed by testing in 'real life' situations, known as beta testing, and then finalising the definite version. Our aim was developing and alpha testing a PtDA for primary treatment of early stage breast cancer, ensuring that the tool is considered relevant, valid and feasible by patients and professionals. METHODS: Our qualitative descriptive study applied various methods including face-to-face think-aloud interviews, a focus group and semi-structured telephone interviews. The study population consisted of breast cancer patients facing the choice between breast-conserving therapy with or without preceding neo-adjuvant chemotherapy and mastectomy, and professionals involved in breast cancer care in dedicated multidisciplinary breast cancer teams. RESULTS: A PtDA was developed in four iterative test rounds, taking nearly 2 years, involving 26 patients and 26 professionals. While the research group initially opted for simplicity for the sake of implementation, the clinicians objected that the complexity of the decision could not be ignored. Other topics of concern were the conflicting views of professionals and patients regarding side effects, the amount of information and how to present it. CONCLUSION: The development was an extensive process, because the professionals rejected the simplifications proposed by the research group. This resulted in the development of a completely new draft PtDA, which took double the expected time and resources. The final version of the PtDA appeared to be well-appreciated by professionals and patients, although its acceptability will only be proven in actual practice (beta testing). TRIAL REGISTRATION: NTR TC 5721 .

Use of 5-azacitidine for therapy-related myeloid neoplasms in patients with concomitant active neoplastic disease.

BACKGROUND: Patients diagnosed with therapy-related myeloid neoplasms (TRMN) with concomitant active neoplastic disorder (CAND) are usually proposed for best supportive care (BSC). We evaluated the feasibility of using 5-azacytidine (AZA) in this setting. METHODS: All patients referred to Gustave Roussy between 2010 and 2015 for TRMN diagnosis (less than 30% blast) and eligible for AZA treatment were included. Patients with CAND proposed for BSC were also described. Patient's outcomes were analyzed based on the presence or not of a CAND. RESULTS: Fifty-two patients with TRMN were analyzed, including 19 patients with CAND (14 eligible for AZA) and 33 without CAND eligible for AZA. The 5 patients with CAND ineligible for AZA had a worst performance status (p=0.016) at diagnosis and a shorter overall survival (OS) (0.62 months). Baseline characteristics of patients eligible for AZA were similar in the 2 groups except a trend for best performance status in patients with CAND (p=0.06). Overall response rate (71.4% vs 60.3%), transfusion independence (50.0% vs 45.5%) and OS (12.7 months vs 10.8 months) were similar between patients with and without CAND respectively (p=ns). CONCLUSION: Here we report the feasibility and efficacy of AZA for selected patients with TRMN and a CAND.

Radioimmunotherapy ((90) Y-Ibritumomab Tiuxetan) for Posttransplant Lymphoproliferative Disorders After Prior Exposure to Rituximab.

Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening complications after solid organ and hematopoietic stem cell transplantation. Only half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain poor for patients with relapsed/refractory disease, especially those who do not qualify for an anthracycline containing regimen due to frailty or comorbidities. Radioimmunotherapy (RIT) might be an option in this particular setting. We report a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs including three ineligible for subsequent CHOP-like chemotherapy who received (90) Y-Ibritumomab tiuxetan as a single agent (n = 7) or combined to chemotherapy (n = 1). Five out of eight patients were kidney transplant recipients, while 2/8 had a liver transplant and 1/8 had a heart transplant. Patients received a median of two previous therapies. Overall response rate was 62.5%. Importantly, all responders achieved complete response. At a median follow-up of 37 months [5; 84], complete response was ongoing in four patients. Toxicity was predominantly hematological and easily manageable. No graft rejection was noticed concomitantly or following RIT administration despite immunosuppression reduction after diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage RIT for early rituximab refractory PTLDs without any unexpected toxicity.

CXCR4 inhibitors selectively eliminate CXCR4-expressing human acute myeloid leukemia cells in NOG mouse model.

The chemokine receptor CXCR4 favors the interaction of acute myeloid leukemia (AML) cells with their niche but the extent to which it participates in pathogenesis is unclear. Here, we show that CXCR4 expression at the surface of leukemic cells allowed distinguishing CXCR4 (high) from CXCR4(neg/low) AML patients. When high levels of CXCR4 are expressed at the surface of AML cells, blocking the receptor function with small molecule inhibitors could promote leukemic cell death and reduce NOD/Shi-scid/IL-2Rγ(null) (NOG) leukemia-initiating cells (LICs). Conversely, these drugs had no efficacy when AML cells do not express CXCR4 or when they do not respond to chemokine CXC motif ligand 12 (CXCL12). Functional analysis showed a greater mobilization of leukemic cells and LICs in response to drugs, suggesting that they target the interaction between leukemic cells and their supportive bone marrow microenvironment. In addition, increased apoptosis of leukemic cells in vitro and in vivo was observed. CXCR4 expression level on AML blast cells and their migratory response to CXCL12 are therefore predictive of the response to the inhibitors and could be used as biomarkers to select patients that could potentially benefit from the drugs.

Rituximab-cyclophosphamide-dexamethasone combination in the management of autoimmune cytopenias associated with chronic lymphocytic leukemia.

We report our experience on rituximab-cyclophosphamide-dexamethasone (RCD) combination therapy for the treatment of autoimmune disorders (AIDs) in 48 chronic lymphocytic leukemia (CLL) patients. Overall, 81% of patients were relapsing for AID after previous treatment with corticosteroids, splenectomy, rituximab or alemtuzumab. Diagnosis of AID was autoimmune hemolytic anemia (AIHA) in 26 (54%), autoimmune thrombocytopenia (AITP) in 9 (18.8%), Evan's syndrome in 8 (16.7%) and pure red cell aplasia (PRCA) in 5 patients (10.5%). Median time of autoimmune disorder (AID) onset from CLL diagnosis was 60 months (range: 0-240), and CLL was considered progressive in 40% of subjects upon AID diagnosis (complex AID). Median hemoglobin pre-treatment was 7.7 g/100 ml, and median platelet count 36.5 × 10(9)/l, returning to a median of 12.5 /100ml and 37.5 × 10(9)/l, respectively. Overall, an 89.5% response rate was obtained with this combination, irrespective of the AID type. Relapse occurred in 19 patients (39.6%). Median duration of response for autoimmunity (DR-AI) was 24 months, but DR-AI was higher for patients presenting: (1) AID early during CLL course (<3 years), or (2) both PRCA and AIHA. Median time to CLL progression in 48 patients was 16 months, but this time was statistically shorter for Evan's syndrome and AITP patients as compared with AIHA and PRCA patients. This study emphasizes the relevance of CLL-directed immune chemotherapy in the management of CLL-associated AID.

External loads on the limbs of jumping horses at take-off and landing.

Using a force plate, ground reaction force (GRF) patterns at take-off and landing between the hooves and the ground were recorded for all limbs of 5 Dutch Warmbloods jumping a 0.8-m vertical fence from the right-leading canter. Distribution of the GRF and force impulses over the 4 limbs at take-off and landing were considerably different from those recorded at the normal canter. At take-off, the propulsory GRF of the hind limbs were 3 to 5 times higher than at the normal canter, depending on the jumping technique of the horse. At landing, the propulsory GRF were mainly increased in the trailing forelimb and in both hind limbs. The vertical GRF amplitudes and force impulses were of similar magnitude to those at the canter, although increases up to 160% were found in the hind limbs of the horse with the worst jumping technique. The trailing forelimb carried the highest loads, up to twice the animal's body weight; GRF amplitudes tended to increase when higher fences were used. However, the jumping technique of the horse may have more influence, because an easily jumping horse could clear a 1.3-m-high fence with similar loads on the limbs.