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1.
Blood ; 141(1): 11-21, 2023 01 05.
Article in English | MEDLINE | ID: mdl-36054922

ABSTRACT

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (<30 × 109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and the incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and nonpregnant women with ITP (53.4 per 100 person-years [95% confidence interval {CI}, 40.8-69.9] vs 37.1 [95% CI, 27.5-50.0]; hazard ratio {HR}, 1.35 [95% CI, 0.89-2.03], P = .16). Pregnant women with ITP were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95% CI, 1.41-5.23], P = .003; HR, 2.01 [95% CI, 1.14-3.57], P = .017, respectively). However, recurrence of severe bleeding events was not different between groups (P = .4). Nineteen (14%) neonates showed NITP <50 × 109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count <50 × 109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95% CI, 1.72-17.89], P = .004 and 4.07 [95% CI, 1.41-11.73], P = .009). To conclude, women with ITP do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling women with ITP.


Subject(s)
Pregnancy Complications, Hematologic , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia, Neonatal Alloimmune , Infant, Newborn , Female , Humans , Pregnancy , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/therapy , Purpura, Thrombocytopenic, Idiopathic/complications , Cohort Studies , Prospective Studies , Pregnancy Complications, Hematologic/epidemiology , Pregnancy Complications, Hematologic/therapy , Thrombocytopenia, Neonatal Alloimmune/therapy , Retrospective Studies
2.
Blood ; 141(23): 2867-2877, 2023 06 08.
Article in English | MEDLINE | ID: mdl-36893453

ABSTRACT

Sustained response off treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in immune thrombocytopenia (ITP). This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response (CR) on TPO-RAs. The primary end point was the proportion of patients achieving SROT (platelet count >30 × 109/L and no bleeding) at week 24 (W24) with no other ITP-specific medications. Secondary end points included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with a median age of 58.5 years; 30 of 48 had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27 of 48 achieved SROT, 15 of 48 achieved SCROT at W24; 25 of 48 achieved SROT, and 14 of 48 achieved SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients rechallenged with TPO-RA, 11 of 12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA sequencing revealed enrichment of a tumor necrosis factor α signaling via NF-κB signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based on progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03119974.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Adult , Humans , Middle Aged , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Platelet Count , Thrombocytopenia/drug therapy , Autoimmunity , Thrombopoietin/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Receptors, Fc/therapeutic use , Hydrazines/therapeutic use
3.
Br J Haematol ; 204(4): 1476-1482, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38267268

ABSTRACT

The aim of this study was to assess the prevalence and the burden of difficult-to-treat primary ITP (pITP), defined by the need for another ITP treatment after romiplostim and eltrombopag. Adult patients were selected in the prospective, real-world CARMEN-France registry up to December 2021. Out of 821 adult patients with pITP, 29 had difficult-to-treat ITP (3.5%; 95% confidence interval [CI]: 2.3%-4.8% in total; 7.6%; 95% CI: 4.9%-10.2% of patients needing ≥2nd line treatment). The 3-year cumulative incidence of bleeding, infection and thrombosis was 100%, 24.1% and 13.8% respectively. The median cumulative duration of hospital stays was 31 days (median follow-up: 30.3 months).


Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Adult , Humans , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/therapy , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Prevalence , Prospective Studies , Thrombopoietin/adverse effects , Receptors, Fc , Benzoates/adverse effects , Hydrazines/adverse effects , France/epidemiology , Registries , Recombinant Fusion Proteins
4.
Br J Haematol ; 198(3): 535-544, 2022 08.
Article in English | MEDLINE | ID: mdl-35438802

ABSTRACT

In order to improve the outcome observed with azacitidine (AZA) in higher-risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA-PLUS was a phase II trial that, in a "pick a winner" approach, randomly assigned patients with higher-risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA-LEN And AZA-IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy-related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our "pick a winner" randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Azacitidine , Leukemia, Myeloid, Acute , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/therapeutic use , Humans , Idarubicin/therapeutic use , Lenalidomide/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Mutation , Treatment Outcome , Valproic Acid/therapeutic use
5.
Blood ; 136(26): 3056-3061, 2020 12 24.
Article in English | MEDLINE | ID: mdl-32814348

ABSTRACT

Management of immune thrombocytopenia (ITP) during pregnancy can be challenging because treatment choices are limited. Thrombopoietin receptor agonists (Tpo-RAs), which likely cross the placenta, are not recommended during pregnancy. To better assess the safety and efficacy of off-label use of Tpo-RAs during pregnancy, a multicenter observational and retrospective study was conducted. Results from 15 pregnant women with ITP (pregnancies, n = 17; neonates, n = 18) treated with either eltrombopag (n = 8) or romiplostim (n = 7) during pregnancy, including 2 patients with secondary ITP, were analyzed. Median time of Tpo-RA exposure during pregnancy was 4.4 weeks (range, 1-39 weeks); the indication for starting Tpo-RAs was preparation for delivery in 10 (58%) of 17 pregnancies, whereas 4 had chronic refractory symptomatic ITP and 3 were receiving eltrombopag when pregnancy started. Regarding safety, neither thromboembolic events among mothers nor Tpo-RA-related fetal or neonatal complications were observed, except for 1 case of neonatal thrombocytosis. Response to Tpo-RAs was achieved in 77% of cases, mostly in combination with concomitant ITP therapy (70% of responders). On the basis of these preliminary findings, temporary off-label use of Tpo-RAs for severe and/or refractory ITP during pregnancy seems safe for both mother and neonate and is likely to be helpful, especially before delivery.


Subject(s)
Benzoates/administration & dosage , Hydrazines/administration & dosage , Pregnancy Complications, Hematologic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Pyrazoles/administration & dosage , Receptors, Fc/administration & dosage , Receptors, Thrombopoietin , Recombinant Fusion Proteins/administration & dosage , Thrombopoietin/administration & dosage , Adult , Benzoates/adverse effects , Female , Follow-Up Studies , Humans , Hydrazines/adverse effects , Pregnancy , Pyrazoles/adverse effects , Recombinant Fusion Proteins/adverse effects , Retrospective Studies , Thrombopoietin/adverse effects
6.
Transfusion ; 62(5): 961-973, 2022 05.
Article in English | MEDLINE | ID: mdl-35452143

ABSTRACT

BACKGROUND: MDS-RS patients are characterized by chronic anemia and a low risk of Acute Myeloid Leukemia (AML) progression and they generally become Red Blood Cell (RBC) transfusion dependent (TD). STUDY DESIGN AND METHODS: We performed a retrospective "real-life" observational study of 6 months in 100 MDS-RS TD patients, recruited in 12 French centers, to describe transfusion characteristics, and evaluate the frequency and causes of hospitalizations, health costs, and morbidity, associated with transfusion dependency, in a French population of RBC transfusion-dependent MDS-RS patients. RESULTS: 79% of the patients had high transfusion burden (HTB) and 21% low transfusion burden (LTB). HTB patients had a longer disease duration (6 vs. 3.7 years, p = 0.0078), more frequent iron chelation (82% vs. 50%, p = 0.0052) and higher serum ferritin (p = 0.03). During the 6-month study period, 22% of the patients required inpatient hospitalization, 36% of them for symptomatic anemia requiring emergency RBC transfusion. The 6-month median transfusion costs, including the cost of the day care facility, transportation to and from the hospital, iron chelation, and lab tests, was 16,188€/patient. DISCUSSION: MDS-RS represents the archetypal type of chronically transfused lower-risk MDS. Most of those patients have a high transfusion burden and thus frequently need visits to the hospital's day care facility, and frequent hospitalizations, with an overall high median treatment cost. Those costs should be compared with costs of new treatments potentially able to avoid RBC transfusion dependence and to reduce the complications of chronic anemia in MDS-RS patients.


Subject(s)
Anemia , Myelodysplastic Syndromes , Anemia/complications , Anemia/therapy , Erythrocyte Transfusion/adverse effects , Humans , Iron Chelating Agents , Myelodysplastic Syndromes/epidemiology , Retrospective Studies
7.
Am J Hematol ; 97(1): 10-17, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34661954

ABSTRACT

Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval of thrombopoietin receptor agonists (TPO-RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO-RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicenter retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defined according to international criteria. We included 185 patients, 100 (54.1%) and 135 (73.0%) patients had received TPO-RAs and/or rituximab before the splenectomy. The median follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) patients had an initial response and 23 (12.4%) experienced relapse during follow-up, for an overall sustained response of 65.4%, similar to that observed in the pre-TPO-RA era. Among patients who received at least one TPO-RA or rituximab before splenectomy, 92/151 (60.9%) had a sustained response. Six of 13 (46%) patients with previous lack of response to both TPO-RAs and rituximab had a sustained response to splenectomy. Among patients with relapse after splenectomy, 13/21 (61.2%) patients responded to one TPO-RAs that failed before splenectomy. In conclusion, splenectomy is still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients with lack of response or with relapse after splenectomy should be re-challenged with TPO-RAs.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic/surgery , Receptors, Thrombopoietin/agonists , Splenectomy , Adult , Female , Humans , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Retrospective Studies , Rituximab/therapeutic use , Treatment Outcome
10.
Haematologica ; 104(3): 497-504, 2019 03.
Article in English | MEDLINE | ID: mdl-30287621

ABSTRACT

Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level <10 g/dL. Patients could be red blood cell transfusion-dependent or not and were given epoetin zeta 40 000 IU/week. Serum erythropoietin level, iron parameters, hepcidin, flow cytometry Ogata and RED scores, and growth-differentiation factor-15 levels were determined at baseline, and molecular analysis by next-generation sequencing was also conducted. Erythroid response (defined according to the International Working Group 2006 criteria) was assessed at week 12. Seventy patients, with a median age of 78 years, were included in the study. There were 22 patients with refractory cytopenia with multilineage dysplasia, 19 with refractory cytopenia with unilineage dysplasia, 14 with refractory anemia with ring sideroblasts, four with refractory anemia with excess blasts-1, six with chronic myelomonocytic leukemia, two with del5q-and three with unclassifiable myelodysplastic syndrome. According to the revised International Prognostic Scoring System, 13 had very low risk, 47 had low risk, nine intermediate risk and one had high-risk disease. Twenty patients were transfusion dependent. Forty-eight percent had an erythroid response and the median duration of the response was 26 months. At baseline, non-responders had significantly higher RED scores and lower hepcidin:ferritin ratios. In multivariate analysis, only a RED score >4 (P=0.05) and a hepcidin:ferritin ratio <9 (P=0.02) were statistically significantly associated with worse erythroid response. The median response duration was shorter in patients with growth-differentiation factor-15 >2000 pg/mL and a hepcidin:ferritin ratio <9 (P=0.0008 and P=0.01, respectively). In multivariate analysis, both variables were associated with shorter response duration. Erythroid response to epoetin zeta was similar to that obtained with other erythropoiesis-stimulating agents and was correlated with higher baseline hepcidin:ferritin ratio and lower RED score. ClinicalTrials.gov registration: NCT 03598582.


Subject(s)
Erythropoiesis/drug effects , Erythropoietin/therapeutic use , Ferritins/blood , Hepcidins/blood , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/drug therapy , Aged , Aged, 80 and over , Biomarkers , Erythropoietin/administration & dosage , Erythropoietin/adverse effects , Female , Flow Cytometry , Humans , Iron/metabolism , Kaplan-Meier Estimate , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/etiology , Prognosis , ROC Curve , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Treatment Outcome
11.
Am J Hematol ; 94(12): 1314-1324, 2019 12.
Article in English | MEDLINE | ID: mdl-31489694

ABSTRACT

Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety. We conducted a prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow-up to assess its long-term safety and efficacy. The median follow-up was 68.4 [53.7-78.5] months. The incidence of severe infections was only 2/100 patient-years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5-83.9] years, corresponding to a mortality rate of 2.3/100 patient-years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow-up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%. As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic/drug therapy , Rituximab/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Adult , Agammaglobulinemia/chemically induced , Agammaglobulinemia/epidemiology , Aged , Aged, 80 and over , Autoimmune Diseases/epidemiology , Autoimmune Diseases/etiology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cause of Death , Disease-Free Survival , Drug Eruptions/epidemiology , Drug Eruptions/etiology , Drug Substitution , Female , Follow-Up Studies , France/epidemiology , Humans , Infections/epidemiology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/etiology , Neoplasms/immunology , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Outcome , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/mortality , Registries , Rituximab/adverse effects , Serum Sickness/chemically induced , Serum Sickness/epidemiology
12.
Blood ; 128(12): 1625-30, 2016 09 22.
Article in English | MEDLINE | ID: mdl-27354722

ABSTRACT

Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio [OR], 4.84; 95% confidence interval [CI], 1.31-17.86; P = .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P = .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6-32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n = 2; sepsis n = 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease.


Subject(s)
Antineoplastic Agents/therapeutic use , Drug Resistance , Purpura, Thrombocytopenic, Idiopathic/therapy , Receptors, Fc/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Rituximab/therapeutic use , Splenectomy/adverse effects , Thrombopoietin/therapeutic use , Adolescent , Adult , Aged , Case-Control Studies , Child , Chronic Disease , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young Adult
13.
Eur J Haematol ; 2018 May 02.
Article in English | MEDLINE | ID: mdl-29719933

ABSTRACT

OBJECTIVES: To assess the reduction of transfusions rate in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) with iron overload treated with deferasirox. METHODS: Prospective observational study. Primary endpoint was reduction in transfusion requirements (RTR) at 3 months, (assessed on 8-week period). Secondary endpoints were hematologic improvement according to International Working Group (IWG) 2006 criteria at 3, 6, and 12 months. RESULTS: Fifty-seven patients were evaluable. After 3 months of chelation, no effect was seen on transfusion requirement (5.9 packed red blood cells (PRBC) vs 5.8 before chelation). According to the Kaplan-Meier analysis, the probability of RTR at 3, 6, and 12 months was assessed as 3.5%, 9.1%, and 18.7%, respectively. Median duration of RTR was 182 days. However, during the 12-month follow-up after deferasirox initiation, 17 patients (31.5%) achieved minor erythroid response [HI-E] according to IWG criteria, 10 of whom having achieved Hb improvement at month 12. CONCLUSION: After 3 months of treatment, deferasirox had no impact on transfusion requirement in regularly transfused patients with low-risk MDS. However, deferasirox could induce 31% of erythroid response during the 12-month follow-up period thus suggesting that iron chelation therapy with deferasirox may induce an effect on hematopoiesis in a subset of patients with MDS and iron overload.

15.
Transfusion ; 57(2): 296-302, 2017 02.
Article in English | MEDLINE | ID: mdl-27861958

ABSTRACT

BACKGROUND: There is increasing evidence that excessive blood transfusion may be associated with impaired survival or cardiovascular events. One way to reduce the number of red blood cells (RBCs) is to transfuse 1 unit (1RBC) instead of 2 units of RBCs (2RBC). STUDY DESIGN AND METHODS: Patients requiring blood transfusions in hematologic intensive care unit were included in a prospective study using a single RBC unit per transfusion and were compared with an historical cohort who received 2 RBC units per transfusion. RESULTS: A total of 1323 units were transfused to 126 patients between 2013 and 2014. The 186 patients in the comparative cohort received a total of 1824 RBC units in a 2-RBC-unit policy between 2010 and 2012. The mean number of units was 7.35 (SD, 5.9 units; 95% confidence interval [CI], 6.5-8.2 units) in the 1RBC group and 8.14 units (SD, 6.2 units; 95% CI, 7.3-8.9 units) in the 2RBC group. The absolute mean difference was -0.79 (95% CI, -1.98 to 0.40; p = 0.09). In the 1RBC allogeneic hematopoietic stem cell transplantation (allo-HSCT) subgroup, a significant reduction in the number of RBC units transfused was observed in comparison with the historical 2RBC allo-HSCT group (5 units vs. 7.7 units; p = 0.01). No anemia-related side effects were reported. Overall survival did not differ between the two groups. CONCLUSION: The 1RBC transfusion policy made is feasible in patients with transient hematologic toxicity after chemotherapy. The number of units transfused between the two groups was not different. However, in the allo-HSCT group, the use of a single RBC unit reduced significantly RBC consumption. A randomized trial comparing the two strategies is planned with a medicoeconomic evaluation.


Subject(s)
Critical Care/methods , Erythrocyte Transfusion , Hematologic Neoplasms/therapy , Adult , Aged , Disease-Free Survival , Female , Hematologic Neoplasms/mortality , Humans , Intensive Care Units , Male , Middle Aged , Prospective Studies , Survival Rate
18.
Blood ; 124(22): 3228-36, 2014 Nov 20.
Article in English | MEDLINE | ID: mdl-25293768

ABSTRACT

We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m(2) and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician's preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 10(9)/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/adverse effects , Cause of Death , Disease-Free Survival , Female , Humans , Male , Middle Aged , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Recurrence , Registries , Rituximab , Treatment Outcome
19.
Haematologica ; 101(3): 336-45, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26703963

ABSTRACT

Quantification of minimal residual disease may guide therapeutic strategies in mantle cell lymphoma. While multiparameter flow cytometry is used for diagnosis, the gold standard method for minimal residual disease analysis is real-time quantitative polymerase chain reaction (RQ-PCR). In this European Mantle Cell Lymphoma network (EU-MCL) pilot study, we compared flow cytometry with RQ-PCR for minimal residual disease detection. Of 113 patients with at least one minimal residual disease sample, RQ-PCR was applicable in 97 (86%). A total of 284 minimal residual disease samples from 61 patients were analyzed in parallel by flow cytometry and RQ-PCR. A single, 8-color, 10-antibody flow cytometry tube allowed specific minimal residual disease assessment in all patients, with a robust sensitivity of 0.01%. Using this cut-off level, the true-positive-rate of flow cytometry with respect to RQ-PCR was 80%, whereas the true-negative-rate was 92%. As expected, RQ-PCR frequently detected positivity below this 0.01% threshold, which is insufficiently sensitive for prognostic evaluation and would ideally be replaced with robust quantification down to a 0.001% (10-5) threshold. In 10 relapsing patients, the transition from negative to positive by RQ-PCR (median 22.5 months before relapse) nearly always preceded transition by flow cytometry (4.5 months), but transition to RQ-PCR positivity above 0.01% (5 months) was simultaneous. Pre-emptive rituximab treatment of 2 patients at minimal residual disease relapse allowed re-establishment of molecular and phenotypic complete remission. Flow cytometry minimal residual disease is a complementary approach to RQ-PCR and a promising tool in individual mantle cell lymphoma therapeutic management. (clinicaltrials identifiers: 00209209 and 00209222).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/genetics , Lymphoma, Mantle-Cell/diagnosis , Adult , Aged , Antigens, CD/blood , Antigens, CD/genetics , Biomarkers, Tumor/blood , Female , Flow Cytometry , Humans , Immunophenotyping , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/mortality , Male , Middle Aged , Neoplasm, Residual , Pilot Projects , Prognosis , Real-Time Polymerase Chain Reaction , Recurrence , Remission Induction , Survival Analysis
20.
Haematologica ; 101(8): 918-25, 2016 08.
Article in English | MEDLINE | ID: mdl-27229713

ABSTRACT

The efficacy of azacitidine in patients with anemia and with lower-risk myelodysplastic syndromes, if relapsing after or resistant to erythropoietic stimulating agents, and the benefit of combining these agents to azacitidine in this setting are not well known. We prospectively compared the outcomes of patients, all of them having the characteristics of this subset of lower-risk myelodysplastic syndrome, if randomly treated with azacitidine alone or azacitidine combined with epoetin-ß. High-resolution cytogenetics and gene mutation analysis were performed at entry. The primary study endpoint was the achievement of red blood cell transfusion independence after six cycles. Ninety-eight patients were randomised (49 in each arm). Median age was 72 years. In an intention to treat analysis, transfusion independence was obtained after 6 cycles in 16.3% versus 14.3% of patients in the azacitidine and azacitidine plus epoetin-ß arms, respectively (P=1.00). Overall erythroid response rate (minor and major responses according to IWG 2000 criteria) was 34.7% vs. 24.5% in the azacitidine and azacitidine plus epoetin-ß arms, respectively (P=0.38). Mutations of the SF3B1 gene were the only ones associated with a significant erythroid response, 29/59 (49%) versus 6/27 (22%) in SF3B1 mutated and unmutated patients, respectively, P=0.02. Detection of at least one "epigenetic mutation" and of an abnormal single nucleotide polymorphism array profile were the only factors associated with significantly poorer overall survival by multivariate analysis. The transfusion independence rate observed with azacitidine in this lower-risk population, but resistant to erythropoietic stimulating agents, was lower than expected, with no observed benefit of added epoetin, (clinicaltrials.gov identifier: 01015352).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/therapeutic use , Drug Resistance , Myelodysplastic Syndromes/drug therapy , Aged , Azacitidine/administration & dosage , Biomarkers , Cytogenetic Analysis , DNA Mutational Analysis , Erythropoietin/administration & dosage , Female , Hematinics/therapeutic use , Humans , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/mortality , Polymorphism, Single Nucleotide , Recombinant Proteins/administration & dosage , Survival Analysis , Treatment Outcome
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