Background: There is a high unmet medical need for therapeutic options for patients suffering from myeloproliferative neoplasms (MPN), who have failed or are not eligible to available treatment options. Ropeginterferon-alfa-2b (P1101) is a novel, third generation pegylated interferon-alfa, recently approved by EMA to treat polycythemia vera (PV). Ropeginterferon-alfa-2b is also in the late stages of development in several countries for treatment of PV and other MPNs. Aims: Ropeginterferon-alfa-2b is a new and attractive treatment option for patients suffering from MPN who have exhausted all therapeutic options and require treatment. The Compassionate Use Program (CUP) was approved and initiated in Taiwan with the purpose of granting access to P1101 to patients with MPN disease with no therapeutic options who are not eligible to enroll in existing clinical trials for their disease. Methods: Patients were identified that had the potential to benefited from P1101 therapy and were eligible according to the protocol. Patients were treated at a starting dose of 250 ug with subsequent dose escalation every 2 weeks over a 6-week period to 350 ug, 450 ug and 500 ug. Dose adjustments were permitted based on tolerability and efficacy. Results: The CUP currently contains 15 patients from two academic hospitals: 9 with PV, 2 with post-PV myelofibrosis (MF), two with pre-fibrotic MF, one with primary MF, and one essential thrombocythemia patient. The driver mutation was JAK2 in 13 patients, CALR in one, and another one was triple negative. Pre-treatment with hydroxyurea and/or anagrelide was reported in 13 patients. P1101 was given for > 12 weeks to 14 patients (range 4 -64 weeks). The highest administered dose of P1101 was: 500 ug in 11 patients (time to highest dose -6 weeks in 9 patients, 10 weeks -in 1 and 20 weeks in another patient); 250 ug, 350 ug and 450 ug in three other patients. The need to decrease or temporarily interrupt P1101 therapy occurred in 4 patients, all due to transaminase(s) elevation. Notably, these events did not require permanent discontinuation of therapy and could be alleviated by appropriate dose modifications. The majority of observed adverse events were of grade 1 and included fatigue, arthralgia, myalgia, chills and dizziness. Grade 2 events included elevation of transaminases (in 3 patients), dizziness, pruritus and lower limbs pain (in 1 patient each). One patient developed elevation of transaminases of grade 3. Normalization of blood parameters within complete hematologic response range was observed in 3 PV and 2 post-PV MF patients. Two PV patients fulfilled the partial response criteria. In other patients, decrease of platelet count (even in previously treatment-resistant thrombocytosis) and symptomatic improvement were also observed. No major cardiovascular events were recorded. One pre-PMF patient transformed into MF (grade 5). No patients progressed to acute myelogenous leukemia (AML) during the observation. Summary/Conclusion: In this cohort of MPN patients, not amenable for establishe...
INTRODUCTION: Neurological complications (NC) are frequently reported after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but their incidence, characteristics and impact on the overall survival are not well defined. For this reason, we retrospectively analyzed our experience. PATIENTS AND METHODS: A retrospective study of 506 allo-HSCTs performed in our center from January 2000 to September 2013, including 336 myeloablative and 170 non-myeloablative, 280 sibling and 226 unrelated, and 397 matched and 109 mismatched. All neurological complications, according to NCCN classification, were included. RESULTS: Seventy seven patients developed neurological complications. Their median age was 48 years (5-70) and 43 (56%) were male. Underlying diseases were Acute Leukemia (34), Myelodysplastic Syndrome (11), Multiple Myeloma (9), Non-Hodgkin Lymphoma (7), Myeloproliferative disease (7), Bone marrow Aplasia (5), Hodgkin Lymphoma (2) and other (2). Thirty eight patients (49.4%) were in CR, 14 (18.2%) in PR, 16 (20.8%) had a refractory disease and 9 (11.7%) had a stable disease. Median preceding treatments were 2 (0-10), including in 24 (31.2%) a preceding HSCT (19 autologous and 5 allogeneic). Fifty seven patients (74%) had received a myeloablative (MA) regimen (14 TBI and 43 chemotherapy). Stem cell source was bone marrow, peripheral blood and umbilical cord blood in 53, 20 and 4 patients, respectively. The donor was unrelated in 47 patients (61%) and mismatched in 25 (32.5%). A calcineurin inhibitor (Cyclosporine or Tacrolimus) was included in all cases as GVHD prophylaxis, combined with Methotrexate (37), Mycophenolate (35) and Prednisone (5). Seventy seven patients developed 81 NC (74 central and 7 peripheral). The global incidence was 16%, being more frequently reported in unrelated (21.4% vs. 11.4%, p=0.002) or mismatched (24.5% vs. 13.5%, p=0.007) allo-HSCT. Within the group who developed central NC, 48 patients (65%) had an early onset (less than 100 days after HSCT), which consisted of impairment of consciousness (36 patients), focal syndrome (22 patients) or seizures (16 patients). The etiology was toxic-metabolic in 32 patients (posterior encephalopathy in 10 cases), infectious in 21 (viral 10, fungal 6, bacterial 5), vascular in 12 (Thrombotic Thrombocytopenic Purpura 6, hemorrhagic 4, ischemic 2) and relapse in 9. Within the group who developed peripheral NC, 5 patients (71.5%) had a late onset, which consisted of polyneuropathy. The etiology was infectious in 2 cases (viral) and immune in 5 cases. Twenty four patients are alive (31.2%) with a median follow-up of 10 months (0-110). Excluding relapses, NC was a direct or indirect cause of death in 24 patients (54.5%), due to viral (9) and fungal (8) infections, above all. The development of a NC, specially in the central nervous system, had a negative impact on the overall survival (17 months vs. 40 months; p=0.001) (figure 1) CONCLUSIONS: In our series, the incidence of NC in the setting of allo-HSCT was 16%, being more frequently found with unrelated and mismatched donor. They were associated with high mortality, having a negative impact on the overall survival and becoming a direct or indirect cause of death in more than half of cases. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
Introduction: Plasmacytomas are uncommon malignant lesions in the breast. Further knowledge is needed about the presentation, diagnosis, and therapy of this disease. Case report: A 78-year-old woman had a previous diagnosis of sacral bone plasmacytoma in March 2005 that was treated with radiotherapy. A new lesion involved in the cervical spine in 2008 was also irradiated. A mammogram and ultrasound found two well-defined nodules in January 2012 in the upper outer quadrant of the right breast, with a total diameter of 38 mm. Biopsy showed a proliferation of cells with Ki-67 staining in more than 90% and positivity for CD38, CD138, CD45, and CD79A, an exclusive expression of lambda light chains. The pathological diagnosis was anaplastic plasmacytoma. She received radiotherapy with remission of the breast lesions. After further appearance of bone lesions, she started chemotherapy with bortezomib, melphalan, and prednisone in January 2016. A PET study in July 2016 showed, among other findings, the presence of a 4-cm lesion in the upper-outer quadrant of the left breast (SUVmax: 3.9). Biopsy gave a diagnosis of plasmacytoma, with cells staining strongly positive for CD138, MUN1, and CD38, with the expression of lambda light chain. Chemotherapy was changed to lenalidomide plus dexamethasone. A further PET in January 2017 displayed, among other findings, the persistence of the lesion in the left breast (SUVmax: 5.4) with two new lesions in the right breast (SUVmax: 5.3 and 13). There was also a sacral progression, and chemotherapy was changed to pomalidomide, dexamethasone plus cyclophosphamide. The evolution of the patient was unfavorable, and she died in June 2017. Criteria for multiple myeloma were not present along the course of the disease. Conclusion: Evolution to bilateral involvement, relapse in the same breast, and refractoriness to chemotherapy are remarkable aspects of this case report and give further information about this presentation of the disease.
BACKGROUND AND OBJECTIVES. Post transplantation High dose Cyclophosphamide (PTCY) used in haploidentical hematopoietic transplantations, has a high effectivity in acute Graft versus Host Disease (aGVHD), and chronic Graft versus Host Disease prophylaxis (cGVHD), however it is associated with high relapse rates. On the other hand, Anti-T-Lymphocyte Globulin (ATG-Fresenius ®) is also effective as immunosuppressive (IS) drug, but its benefit on Overall Survival (OS) and Relapse Free Survival (RFS) is unclear. The aim of this study was to compare the effectiveness of two GVHD prophylaxis regimes used in high risk transplantation: PTCY used in Haploidentical transplantation and ATG used for peripheral blood, non-related, related and mismatched donors. The primary endpoint was to evaluate the incidence of aGVHD and cGVHD, and its severity in both groups. As secondary endpoints we analyse the OS, RFS and GRFS (recorded adverse events include grade 3-4 aGVHD, systemic therapy-requiring cGVHD, relapse or death during median follow-up). We also consider transplantation related mortality (TRM) and post-transplantation complications. PATIENTS AND METHODS. We retrospectively analyse 111 allo-transplantations performed at our institution between 2012 and 2017. We analyse two cohorts: 49 haploidentical transplantation with PTCY (50 mg/kg, on day +3, +4) followed by Tacrolimus and Mycophenolate; and 62 peripheral blood related, non-related and mismatched with low dose ATG Fresenius (7mgr/Kg on days -3, -2, -1) associated with Tacrolimus/Cyclosporine starting on day -1 with a short course Methotrexate (on day +1, +3, +6) or Mycophenolate. Mycophenolate was stopped on day +28 and Cyclosporine or Tacrolimus were tapered on day +50. RESULTS. There were no differences in patients' age (49 vs 51), sex or pre-transplantation HCTI-score ≥ 3 (30 vs 26) between PTCY and ATG groups. We found differences between diagnosis (lymphoproliferative disorders (16 vs 4, p= 0.003), high DRI-score (18 vs 11, p = 0.04), number of previous transplantations (12 vs 5, p= 0.02), reduced intensity conditioning regimen (36 vs 20, p < 0.001) and bone marrow as stem cells source (38 vs 9, p < 0.001) between PTCY and ATG groups. The median time to neutrophil engraftment (>500/uL) was similar: 17 days [13-34] for PTCY and 16 days [9-33] for ATG. Median time to platelet recovery was higher in PTCY cohort (33 vs 18 days, p= 0.016). There were 3 secondary graft failures in PTCY group vs 4 graft failures in ATG (3 primary, 1 secondary). The were no differences in grade 2 - 4 aGVHD incidence between groups (PTCY:30.6% vs ATG:36.4%), but we found differences in grades 3 - 4 aGVHD (PTCY:4.1% vs ATG: 9%, p=ns). The global incidence of any NIH grade cGVHD was 56.1% in PTCY vs 66% in ATG group. Mild, moderate and severe cGVHD incidence were 31.7%, 19.5% and 4.8% for PTCY vs 28%, 26% and 12% in ATG (p=ns). The median duration of IS in alive patients with cGVHD was 6.5 months [3-19] in PTCY patients and 10 [3-34] in ATG group. Among moderate and severe forms, the median IS duration was 10 and 5 months in PTCY group vs 13 and 12 months in ATG respectively. PTCY cohort developed more non-infectious complications, especially, cardiac, lung, digestive and neurologic complications, (p=0.086), however there were not differences in infectious complications (Table 1). TRM was similar between groups, 18.4% for PTCY vs 22.5% for ATG, (p=0.250). We didn´t find differences in early toxic mortality (<100 days): 16.3% for PTCY and 14.5% for ATG (p=0,421). With a median follow-up of 27 months in alive patients (28 months for PTCY and 22 months for ATG) we report an 67.8 % and 61% OS at 12 and 24 months for PTCY and 68.8% and 59.9% for ATG (Log Rank=0.971). Relapse free survival at 12 and 24 months was 61% and 57.9% for PTCY and 69% and 54% for ATG (Log Rank=0.839). GRFS at 12 and 24 months was 46.5% and 42.9% for PTCY patients and 40.7% and 33% for ATG patients, (Log Rank = 0.433). CONCLUSIONS. Regardless the different scenarios between transplantation cohorts, the use of PTCY and low dose ATG are equally effective in the prophylaxis of severe forms of aGVHD and cGVHD, offering similar GRFS. PTCY shows higher early toxicity but a similar rate of infectious events. In order to validate these results, it would be necessary to carry out a randomized controlled trial. Disclosures No relevant conflicts of interest to declare.
Background Patients undergoing hematopoietic stem cell transplantation (HSCT) are at high risk of multiple complications being graft versus host disease (GvHD) one of the most concerning. Addition of anti-T-lymphocyte globulin (ATG-Fresenius ®) reduces the incidence of acute and chronic GvHD however, optimal dose has not yet been established. Standard dose (60 mg/kg) has shown a significantly lower moderate-severe cGvHD yet its effect in Progression Free Survival (PFS) and Overall Survival (OS) is contradictory. Our primary objective was to analyze the efficacy of low ATG dose (21 mg/kg) in the prophylaxis of acute and chronic GvHD. As secondary objective we analyzed non-relapse mortality (NRM), infectious and non-infectious complications, GvHD and relapse free survival (GRFS), overall survival and progression free survival in high risk patients undergoing HSCT. Patients and methods We retrospectively analyzed 57 patients who underwent HSCT in our center from 2012 to 2017, receiving a total dose of 21 mg/kg (7 mg/kg on day -3, -2 and -1) of ATG as part of the GvHD prophylaxis, associated to cyclosporine/tacrolimus and MMF/short course-MTX. The conditioning regimen were myeloablative in 42 patients (73.7%). The donor was unrelated in 46 cases (80.7%). Seventeen (29.9%) had a mismatch (16 unrelated, 1 sibling). Stem cell source was peripheral blood in 51 patients (89.4%). Forty six (80.7%) patients were positive for CMV, from these 17 (36.9%) were paired with seronegative donors. The median age was 57 years old (18-70), 38(66.7%) were males. The most frequent diagnosis were Acute Myeloblastic Leukemia (40.4%), myelofibrosis (17.5%) and myelodisplastic syndrome (14%); 28 (49%) had a HCTI score ≥ 3 and 16 (29%) a high risk DRI score. Thirty patients (52.6%) were in complete remission at the moment of HSCT. (Table 1) Results Hematopoietic engraftment was observed in 54 patients (94.7%). The median neutrophil and platelet engraftment were 14 (10-34) and 15 (9-28) days, respectively. Primary graft failure occurred in 3 patients (2 myelofibrosis, 1 AML). Twenty (39.2%) out of 51 evaluable patients developed grade 2-4 acute GvHD. The cumulative incidence of grade 3-4 aGvHD was 8.8% (95% CI, 3.2-17.9%). Skin was the most affected organ (62%). We found a cumulative incidence of moderate to severe cGvHD of 35.2% (95% CI 22.7-47.9%), only 5 cases (10.6%) were severe, with a median onset at day 177 (57-893). The median duration of immunosuppresive systemic therapy was 488 days (207-2046) in the group of patients with moderate to severe cGvHD. Twelve patients died due to transplant related events, 7 were reported before day 100, all of infectious etiology. The NRM at two years was 21.9% (95% CI, 12-33.7%). Eleven patients (19.2%) had at least two episodes of CMV reactivation and one had cytomegalic gastrointestinal disease. One patient developed postransplantation lymphoproliferative disorder associated to Epstein Barr virus. Twenty patients (35%) developed noninfectious complications, being hemorrhagic diathesis, hepatotoxicity and severe mucositis the most frequents. With a median follow up of 28 months in alive patients (3-67), the GRFS at one year, OS and PFS at two years were 47.6% (95% CI, 42.8-52.2%), 59% (95% CI, 54.5-63.2%) and 52% (95% CI, 46.9-56.5%), respectively. The relapse incidence at two years was 26.3% (95% CI 14.7-39.4%). Conclusions In our center, the use of low ATG doses is protective against severe forms of acute GvHD, offering also a moderate protection against chronic GvHD in a cohort with high prevalence of mismatched unrelated donors, high median age and high risk DRI and HCTI. This approach doesn't seem to have a significant negative impact neither in GRFS, OS and PFS at two years. Disclosures No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.