Protective Effect of Rituximab Against Lymphoma Risk In HIV-Associated Multicentric Castleman Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2869-2869
Author(s):  
Jean Marie Michot ◽  
Laurence Gérard, MD ◽  
Claire Fieschi ◽  
Sarah Burcheri ◽  
Eric Oksenhendler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Castleman Disease ◽  
Control Group ◽  
First Line ◽  
Multicentric Castleman Disease ◽  
Median Period ◽  
History Of ◽  
Lymphoma Risk

Abstract Abstract 2869 Human Immunodeficiency Virus (HIV)-associated multicentric Castleman disease (HIV-MCD) is a rare lymphoproliferative disorder occurring in patients co-infected with HHV-8. Long-term prognosis remains severe mainly because of the high incidence of aggressive HHV-8 associated non-Hodgkin lymphoma (NHL). Chemotherapy is usually the first line therapy in active HIV-MCD. Most patients remain dependent on chemotherapy. Recent studies have demonstrated that rituximab allows to resume chemotherapy in most patients. However, effect of rituximab on long-term incidence of lymphoma is unknown. All consecutive patients with HIV-MCD from the national HIV-lymphoproliferative cohort (Clinical site, Saint-Louis Hospital, Paris, France) were enrolled in combination antiretroviral therapy (cART) era. Patients with NHL within the 2 months prior or following rituximab were excluded from analysis. Patients treated with rituximab received 4 infusions, 375 mg per m2 at weekly intervals. Primary objective of the study was to compare incidence of NHL between patients who received rituximab (rituximab group) and who did not received rituximab (control group). Secondary objectives were to compare overall survival and to describe tolerance to rituximab. Survival and NHL incidence was estimated using Kaplan-Meier method and tested with log-rank test. 115 patients with HIV-MCD were included in the HIV-lymphoproliferative cohort until november, 2009. Patients were followed for a mean period of 3 years. 7 patients received rituximab as part of LNH therapy and were excluded from analysis. 33 patients (29%) received rituximab as part of MCD therapy. In rituximab group at MCD diagnosis, mean age was 41 years, 24 patients (73%) received antiretroviral therapy, HIV viral load was undetectable (< 500 c/ml) in 10 patients (30%), median CD4 cell count was 233 × 106/L [IQR, 101–368], median nadir CD4 was 160 × 106/L [IQR, 61–194], 14 patients (42%) had an history of Kaposi sarcoma (KS) before rituximab therapy, which was in complete remission or stable at time of rituximab therapy. All 33 patients received chemotherapy as first line MCD treatment: etoposide (n=27), vinblastine (n=4), anthracyclines (n=2). The median period from MCD diagnosis to rituximab therapy was 7.7 months [IQR, 4.6–23.8]. All but 2 patients received the 4 scheduled infusions. These 2 patients discontinued rituximab after the second infusion; one died at day 15 from progressive MCD and the other one discontinued for investigation of rectal tumor. 4 patients received a second course of 4 rituximab infusions for MCD relapse, after a median period of 19.5 months (IQR, 15 to 23). The 3-years probability of developing lymphoma was 0.04% [95%CI,0.01-0.99] in rituximab group (n=33) and 23% [95%CI,14-34] in control group (n=74) (P=0.001). The only lymphoma in rituximab group occurred 22 months after rituximab therapy and patient died. In rituximab group, the median overall survival was 15.7 years compared to 5.2 years in control group (P=0.0007). During total follow-up, 5 patients (15%) died in rituximab group and 28 patients (38%) died in control group. Causes of death in rituximab group was MCD attack (n=1), lymphoma (n=1), acute myeloid leukemia (n=1), infection (n=1), cardiovascular disease (n=1). No severe adverse event was observed during rituximab infusions. Within the first year following rituximab therapy, 9 patients (27%) developed mild to moderate infections; pneumonia (n=2), herpes reactivation (n=2), enterocolitis (n=2), dacryocystitis (n=1), folliculitis (n=1), staphylococcus catheter-related infection (n=1). Transient grade 3 neutropenia occurred in 2 patients (6%). Exacerbation of KS was observed in 4 out of the 15 patients with prior history of KS (4, 4, 7, 36 months after rituximab therapy, respectively), and required specific treatment in 2 patients. Despite improvement in overall survival of HIV-MCD in cART era, risk for developing lymphoma remains high (23% at 3 years). Rituximab seems to induce long-term protection against lymphoma risk, with only one patient developing lymphoma during the 3-year follow-up period in our cohort. Disclosures: No relevant conflicts of interest to declare.

Improved outcome with rituximab in patients with HIV-associated multicentric Castleman disease

Blood ◽  
2011 ◽  
Vol 118 (13) ◽  
pp. 3499-3503 ◽  
Author(s):  
Christian Hoffmann ◽  
Holger Schmid ◽  
Markus Müller ◽  
Christian Teutsch ◽  
Jan van Lunzen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Antiviral Agents ◽  
Castleman Disease ◽  
Cytostatic Agents ◽  
First Line ◽  
Multicentric Castleman Disease ◽  
Remission Rates ◽  
Potential Risk Factors ◽  
The Mean

Abstract Although HIV-associated multicentric Castleman disease (HIV-MCD) is not classified as an AIDS-defining illness, mortality is high and progression to lymphoma occurs frequently. At present, there is no widely accepted recommendation for the treatment of HIV-MCD. In this retrospective (1998-2010), multicentric analysis of 52 histologically proven cases, outcome was analyzed with respect to the use of different MCD therapies and potential prognostic factors. After a mean follow-up of 2.26 years, 19 of 52 patients died. Median estimated overall survival (OS) was 6.2 years. Potential risk factors, such as older age, previous AIDS, or lower CD4 T cells had no impact on OS. Treatment was heterogeneous, consisting of cytostatic and/or antiviral agents, rituximab, or combinations of these modalities. There were marked differences in the outcome when patients were grouped according to MCD treatment. Patients receiving rituximab-based regimens had higher complete remission rates than patients receiving chemotherapy only. The mean estimated OS in patients receiving rituximab alone or in combination with cytostatic agents was not reached, compared with 5.1 years (P = .03). Clinical outcome and overall survival of HIV-MCD have markedly improved with rituximab-based therapies, considering rituximab-based therapies (with or without cytostatic agents) to be among the preferred first-line options in patients with HIV-MCD.

scholarly journals Prospective Long-Term Follow-up after First-Line Subcutaneous Cladribine Treatment in Patients with Hairy Cell Leukemia. a Study of the SAKK (Swiss Group for Clinical Cancer Research)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2875-2875
Author(s):  
Rudolf A. Benz ◽  
Kornelius Arn ◽  
Martin Andres ◽  
Thomas Pabst ◽  
Urban Novak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Secondary Malignancies ◽  
Hairy Cell ◽  
First Line ◽  
Purine Analogues ◽  
Minor Response ◽  
Kaplan Meier ◽  
Long Term Follow Up

Abstract Introduction : Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with a very indolent clinical course and patients may survive for many decades. First-line treatment with purine analogues such as cladribine (Cld) is considered standard of care since it is very efficient and induces profound remissions. However, patients with HCL often relapse after purine analogues and repeated treatment may increase morbidity and mortality. Despite good clinical evidence of long term control of the disease by several mainly single center studies of patients treated with purine analogues, there is only one study analyzing mainly subcutaneous (sc) treated patients based on registry data. We therefore performed a pooled long-term follow-up analysis of our prospective multicenter studies treating patients with sc Cld focusing on survival, secondary malignancy and retreatment. Materials and Methods : The SAKK included patients treated for HCL in 4 studies between 1993 and 2005. Three studies focused on first-line regimens with sc Cld, whereas the fourth protocol focused on the effect of Rituximab monotherapy in patients pretreated with Cld. Classical morphologic, immunohistochemistry and flow cytometry criteria were used as inclusion criteria and response was assessed by established criteria. Treatment algorithms in the 4 studies were as follows: 1) 5 days of Cld 0.14mg/kg sc followed by max 2 cycles of 7 days of Cld 0.1mg/kg sc in case of minor response or no response (SAKK 32/93); 2) Single shot of Cld 0.25mg/kg sc followed by a maximum of 2 cycles of 0.14mg/kg sc for 5 day in case of minor response, no response or relapse (SAKK 32/95); 3) 5 consecutive days of Cld 0.14mg/kg sc versus the same dose in 5 weekly applications (SAKK 32/98); 4) Rituximab 375 mg/m2iv weekly for 4 weeks in relapsed patients (SAKK 31/98). SAKK 32/93 included 63, SAKK 32/95 74 and SAKK 32/98 100 patients. Of the 26 patients registered in 31/98 20 were already in SAKK 32/93, 32/95 and 32/98. Therefore, we also included the treatment information and follow-up data of these 20 patients. All patients were subject to life-long follow-up within the clinical trials. Further information including secondary malignancies and retreatments were obtained by sending out questionnaires to the treating physicians of the study patients. Of the 237 patients 4 patients were in two of the studies and 10 patients have been excluded because of non-classical HCL phenotype. Therefore, a total of 223 patients were included in the analysis. Overall survival and follow-up time were assessed by Kaplan-Meier and reverse Kaplan-Meier method, respectively. Results : The median age of patients at the time of diagnosis was 55 (range 21 to 96) years, 50 patients were female (22.4%) and 173 (77.6%) male. At the time of data analysis, the median follow-up time was 12.1 (95%-CI 10.0 to 14.0) years. A total of 129 (57.8%) patients had the last follow-up information more than two years prior to the data cut-off in May 2016, however, the available information of all patients was used for the sub-analyses including secondary malignancies or retreatment. By the cut-off date, 49 patients have died, 14 (28.6%) due to secondary malignancies and 7 (14.3%) due to HCL progression. Median overall survival from diagnosis was 31.6 (95%-CI 31.6 to 37.8) years. Retreatment was necessary in 53 (23.7%) patients after a mean of 6 (0.2 to 20.4) years and first retreatment was mainly Cld (64%), rituximab (19%) or Cld and rituximab (13%). 21 patients (9.4%) required more than one retreatment with a mean number of 1.57 (range 1 to 5) treatments. A total of 42 (18.8%) patients developed secondary malignancies with an average time to occurrence of 7.1 (range: 0.1 to 17.7) years. The majority of the secondary malignancies were of non-hematological origin (85.9%), most frequently skin cancer (31.0%), followed by prostate cancer (19.0%) and colorectal cancer (16.7%). Six patients (14.4%) developed hematological secondary malignancies with a predominance of B-lymphoid neoplasms. Conclusion : Long-term overall survival in HCL patients treated with sc Cld was excellent and comparable to studies using iv Cld. Despite the long follow-up, sc Cld had a curative potential and relapses requiring re-treatment were observed only in a minority of patients. Secondary malignancies were predominantly non-hematological. These data indicate that patients need to be followed carefully with a special focus on secondary malignancies. Disclosures Chalandon: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

Outcome of Kidney Transplantation in Patients with Antiphospholipid Antibodies: A Case Series

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1230-1230
Author(s):  
Karen A Breen ◽  
Kaji Sritharan ◽  
Jonathon Olsburgh ◽  
Beverley J Hunt
Keyword(s):  
Kidney Transplantation ◽  
Antiphospholipid Antibodies ◽  
Graft Failure ◽  
Control Group ◽  
Cardiolipin Antibodies ◽  
Long Term Follow Up ◽  
History Of ◽  
Thrombotic Complications

Abstract Abstract 1230 Background: Thrombotic and obstetric complications occur in association with antiphospholipid antibodies (aPL), as do intrarenal vascular changes in primary and secondary APS. There are a limited number of studies reporting the outcome of patients with aPL receiving kidney allografts. Materials & Methods: A retrospective chart review of patients who underwent kidney transplantation in our institution between 2005 and 2010 (inclusive) was performed. Patients who had at least 1 positive aPL at the time of transplantation were identified, their demographic, immediate and long-term outcome details obtained including any aPL related complications (thrombotic episodes including intrarenal vascular complications). Comparison was made with a control group consisting of transplant recipients not known to have aPL, matched for age, sex, transplant type and year of transplant. Results: 884 patients underwent kidney transplantation between 2005 and 2010. 87 patients were screened for aPL(9.8%), 41 patients with aPL were identified(4.6%), 34 patients had a lupus anticoagulant, 1 had anti-cardiolipin antibodies and 6 both lupus anticoagulant and anti-cardiolipin antibodies. Long-term follow up was available for 31 patients. 25/31 patients were found to have persistent aPL (25/31 had repeated aPL screening). Patients included 17 males, 24 females, mean age 42 (range 19–61) years). 14 patients were known to have persistent aPL prior to transplantation and 5 of these were receiving long-term anticoagulation because of a history of thrombosis prior to renal transplant. 3 of the 27 patients not known to have persistent aPL prior to transplantation had a history of thrombosis prior to renal transplant; none of these were receiving long-term anticoagulation. 13 patients had aPL in association with other autoimmune disease (SLE). 30 patients had screening for other thrombophilic disorders performed. Other risk factors included hypercholesterolaemia, hypertension and cigarette smoking. The table below summarises short and long-term aPL related complications. 25 patients had a cadaveric transplant, 2 had live unrelated donor transplants and 14 had live-related donor kidney transplants. Immediate thrombotic complications in patients with aPL included 4 patients who had graft failure due to renal vessel thrombosis resulting in graft excision because of ischaemia of the transplanted organ and 2 had a lower limb DVT (receiving perioperative thromboprophylaxis with aspirin, n=6) compared to 1 patient in the control group who experienced a lower limb DVT(significantly higher in patients with aPL compared to controls p=0.03). Of the patients for whom long term follow up was available, long-term thrombotic complications were significantly higher in patients with aPL compared to controls (5/31 patients with aPL compared to 0/31 controls, p=0.02). Complications included fatal PE in 1 patient (on warfarin with subtherapeutic INR), bowel ischaemia secondary to mesenteric artery occlusion in another (on aspirin), and 1 patient had graft failure 9 months following transplant due to thrombotic microangiopathy (commenced on warfarin 6 months post transplant due to persistent aPL). Renal artery stenosis occurred in 2 patients (both receiving aspirin). Conclusions: There is a high risk of thrombotic complications in patients with aPL who are undergoing renal allograft. These patients should be considered for perioperative and longterm thromboprophylaxis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Short-term skin problems in infants aged 0–3 months affect food allergies or atopic dermatitis until 2 years of age, among infants of the general population

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Kaori Yonezawa ◽  
Megumi Haruna
Keyword(s):  
Atopic Dermatitis ◽  
Family History ◽  
Food Allergies ◽  
Control Group ◽  
Short Term ◽  
Skin Problem ◽  
Significant Difference ◽  
History Of

Abstract Background This study examined whether infants aged 0–3 months exhibited long-term effects of using a moisturizer skincare intervention and whether a short-term skin problem resulted in the subsequent development of food allergies or atopic dermatitis (AD) until the age of 2 years. Methods This study was a follow-up of a completed randomized control trial (RCT) of moisturizer skincare for infants aged 0–3 months. A self-reported questionnaire was mailed to the parents of children aged 1–2 years who had participated in the RCT. Data were analyzed using a Chi square test, by intention to treat analysis, and by multiple logistic regression. Results Of 155 infants, 22 (14.2%) and 28 (18.1%) had food allergies and AD/eczema until 2 years of age, respectively. No significant difference was seen in food allergies or AD between the group that received moisturizer skincare intervention and the control group. On the contrary, food allergies until 2 years of age were significantly associated with short-term (4–7 days) and long-term (more than 7 days) body skin problems occurring in the first 3 months of life, a family history of AD, and the time of starting complementary food. High value of face transepidermal water loss at 3 months of age was also associated with food allergies. Moreover, a short duration of severe diaper dermatitis during the first 3 months, a family history of AD, and being male were significantly associated with AD/eczema until the age of 2 years. Conclusions After adjusting for family history of AD, a short-term skin problem in the first 3 months of life was significantly associated with the development of food allergies or AD/eczema until the age of 2 years. Prevention or prompt treatment of skin problems in newborns is essential for preventing future allergic diseases. Trial registration This was a follow-up study conducted 2 years after the completed RCT of a moisturizer skincare intervention for early infants, which was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000013260)

Rituximab, Endoxan, Ganciclovir, Dexamethasone, Tocilizumab Sequential Treatment In Kaposi's Sarcoma-Associated Herpesvirus (KSHV) -Related Multicentric Castleman Disease. A Case Report with 8 Months Follow-up

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4872-4872
Author(s):  
Francesco Iuliano ◽  
Tecla Mingrone ◽  
Stefania Infusino ◽  
Alessia Perricelli ◽  
Angelo Pomillo ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Sequential Therapy ◽  
Clinical History ◽  
Castleman Disease ◽  
High Grade Fever ◽  
Intravenous Ganciclovir ◽  
Multicentric Castleman Disease ◽  
First Case ◽  
History Of

Abstract Abstract 4872 Clinical history of Kaposi sarcoma-associated herpesvirus (KSHV),-related Multicentric Castleman Disease is characterized by a rapidly progressive and often fatal course. We report a case successfully treated sequentially with a course of 4 infusions of rituximab 375mg/m2 at weekly intervals, Endoxan, 750 mg/m2 as an intravenous infusion once weekly for 2 weeks, intravenous ganciclovir, 5 mg/kg twice daily for 2 weeks and then once daily, dexamethasone 20 mg on days 1–4, 9–12, 17–20 and anti-interleukin-6 receptor antibody (tocilizumab) administered intravenously at a dose of 8 mg/kg every 2 weeks, starting at day 32. On December 12, 2009, a 54-year-old man came to the medicine department because of a 2-week history of progressive fatigue, wasting, high-grade fever (39°C), profuse sweating, and severe autoimmune hemolytic anemia (4.2 mg/dL). He had been diagnosed with asymptomatic MCD 6 months before admission. Generalized lymphadenopathy and hepato-splenomegaly were evident on physical examination and enlarged lymph nodes in retroperitoneal regions (CT scan). Blood biochemistry showed very high CRP, IL-6, beta 2 microglobulin serum levels, low LDH and albumin, increase polyclonal immunoglobulin, grade 3 thrombocytopenia and neutropenia. Serologic tests (Epstein-Barr virus, hepatitis B and C viruses, cytomegalovirus and human immunodeficiency virus) were negative. On hospital day 10, 250.000 copies of HHV-8 DNA were detected in 1 mL plasma by RT-PCR. The patient achieved CR two months after admission, still maintained at 8 month follow-up. HHV-8 DNA became undetectable over the course of 8 weeks, at which time ganciclovir was discontinued. Conclusions: In our case the onset of the disease was serious and life-threatening. Sequential therapy has proven to be able to save the life of the patient acting on different biological targets. To date is the first case treated with this schedule. Disclosures: No relevant conflicts of interest to declare.

The Natural History of Fanconi Anemia: A Report from the Italian Fanconi Anemia Registry (RIAF)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1208-1208
Author(s):  
Serena Marotta ◽  
Antonio M Risitano ◽  
Rita Calzone ◽  
Oriana Catapano ◽  
Adriana Zatterale
Keyword(s):  
Overall Survival ◽  
Natural History ◽  
Fanconi Anemia ◽  
Research Funding ◽  
Disease Course ◽  
Hematopoietic Stem ◽  
History Of ◽  
Hematological Manifestations

Abstract Fanconi anemia (FA) is a rare inherited syndrome characterized by chromosomal instability, eventually resulting in a number of manifestations affecting the hematopoietic system and other organs. The phenotype of FA patients is largely heterogeneous, and encompasses different clinical manifestations that may be present at birth, or rather develop later during the disease course. Thus, even due to the rarity of the disease, the natural history of FA remains hard to be established in its details. To accomplish the need of a large disease registry, in 1994 we have established at the local health unit "ASL Napoli 1" a National Database named as "Registro Italiano Anemia di Fanconi " (RIAF): here we report on a 20-year experience of the Italian FA Registry. Patients were enrolled prospectively at diagnosis or later on, after signature of the informed consent form; epidemiological, genetic and clinical data were recorded at registration, with these latter information eventually collected periodically to assess the clinical course, possible complications and long-term survival. The main endpoint of the study was the description of the natural history, looking for the following variables: family history, disease presentation, development of hematological manifestations, development of malignancies, occurrence of hematopoietic stem cell transplantation (HSCT) and survival. Between 1994 and 2014 a total of 180 patients were included in the RIAF, belonging to 151 distinct families; all diagnoses were based on standard chromosome DEB (diepoxybutane) - or MMC (mytomicin C) - breakage test confirmed at specialized centers. The median age at diagnosis was 3170 days, and it was lower in patients born in the more recent periods; the median follow up of enrolled patient was 15.6 years. For the majority of patients the diagnosis was suspected based on the typical morphological abnormalities and/or growth retardation; congenital abnormalities (mostly skin pigmentation and skeletal abnormalities) were demonstrated in 90% of patients. The majority of patients (77%) exhibited some hematological abnormalities at diagnosis, which in most cases was a mild-to-moderate cytopenia. Looking at the subsequent disease course, a total of 172 (96%) FA patients developed some hematological manifestations, typically progressive cytopenia due to bone marrow failure. The cumulative incidences (CI) of any hematological disorder were 62%, 88% and 94% at 10, 20 and 30 years, respectively, whereas those of a hematological malignancy were 5%, 8% and 22% at 10, 20 and 30 years. Hematological manifestations led to an allogeneic hematopoietic stem cell transplantation (HSCT) in more than half of the patients (57%), with a CI of HSCT of 33%, 64% and 72%% at 10, 20 and 30 years, respectively; patients born in the most recent years were transplanted earlier. The presence at diagnosis of a solid tumor was quite rare; nevertheless, solid tumors were the most significant complication in the long-term period, with a CI of 1%, 15% and 32% at 10, 20 and 30 years respectively; head and neck were the most common cancer sites. Eighty-eight of the 180 FA patients enrolled in the RIAF died during their follow up; in non-transplanted patients, the main causes of death were related to the underlying disease (infections, bleeding, and solid tumors), whereas in transplanted patients graft versus host disease and other transplant-related complications played a major role. The median survival of this large cohort was 22.5 years; overall survival at 10, 20 and 30 years were 88%, 56% and 37%, respectively, with no improvement over the past decades. These data confirm the poor long-term prognosis of FA patients, irrespective of earlier diagnosis and improved treatment options achieved in the most recent years. Figure 1. Overall survival of the 180 patients enrolled in the RIAF Figure 1. Overall survival of the 180 patients enrolled in the RIAF Disclosures Risitano: Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alnylam: Consultancy, Research Funding; Rapharma: Consultancy, Research Funding; Novartis: Research Funding; Pfizer: Consultancy.

Long-Term Outcome after Immunosuppressive Therapy with Rabbit ΑΤG for Pediatric Aplastic Anemia: A Single-Center Retrospective Study in China

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2678-2678
Author(s):  
Jingliao Zhang ◽  
Lixian Chang ◽  
Ye Guo ◽  
Yingchi Zhang ◽  
Tianfeng Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Response Rate ◽  
First Line ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Free Survival ◽  
Time Points

Abstract Background: Antithymocyte globulin (ATG)-based immunosuppressive therapy (IST) has been successfully used as the first-line treatment for severe / very severe aplastic anemia (SAA/VSAA) patients if no HLA-matched sibling donor was eligible for HSCT as a first choice. It was reported rabbit ATG (rATG) produced more profound immunosuppressive activity compared to horse ATG (hATG). However, recent clinical studies indicated that the stronger lympholytic activity did not mean that rATG was more effective. Most experiences from adult SAA/VSAA implied the efficacy of rATG was worse than hATG. However, susceptibility of children to intensive IST might not be exactly the same as adult patients, long-term efficacy of rATG in historic studies for children with SAA/VSAA was still elusive. Purpose: This study includes the largest cohort of pediatric AA patients treated with first-line rATG+CSA regimen published to date after a median follow-up of 69 months, aiming to assess the long-term outcome of rATG for children, and to identify the significant prior factors in clinical decision making. Methods: We reviewed 231 SAA/VSAA patients under 18 years old assigned to rATG+CSA from February 2000 to May 2014 in Department of Pediatrics, the Blood Diseases Hospital & Institute of Hematology, CAMS & PUMC. Response was evaluated 3, 6, 9, 12 24, 36 and 60 months after IST. We separately defined SAA-II as a specific type of gradually progressed SAA from a NSAA status within a longer period for at least 6 months. Multivariate logistic regression models were used to evaluate the effects of variables on the responses at different time points. Multivariate Cox model analysis of overall survival (OS) and failure-free survival (FFS) was calculated for variables with a log rank P value less than 0.1 in Kaplan-Meier analysis. Results: Of the overall patients, the total responded patients were 79(34.3%), 110(51.6%), and 129 (60.6%) at 6, 9, 12 months following IST, respectively. Intriguingly, 22 patients achieved delayed response between 12 months and 24months after IST, which increased the overall response rate by 10.2%, afterwards the rate reached a plateau by 3 years with the best response rate of 74.6% (Figure 1). Differences in baseline clinical parameters pre-IST were associated with response to IST. Absolute neutrophil count (ANC) less than 0.1*109/L was associated with an unfavorable early response rate at 6 months (P=0.009); absolute lymphocyte count (ALC) less than 1.6*109/L was a significant predictor for better response by 6 months and 12 months in multivariate analysis [6 months, P=0.033 vs. 12 months, P=0.021]. Lower absolute reticulocyte count (ARC no more than 18.5*109/L) predicted worse late IST response by 2 years and 3 years. In our large series of cohort, 5-year OS and FFS were 82.7% and 61.9%. Patients with VSAA as a significantly unfavorable prognostic factor had a much lower probability of 5-year survival when compared to patients diagnosed with SAA (76.4% vs. 87.2%, P<0.001, Figure2A). In multivariate analysis, SAA-II (P=0.021, Figure2B), and a pretreatment lower ARC (P=0.020, Figure2C) were independent unfavorable prognostic factors for FFS, but moderate PNH clone size (more than 5%) was verified as a good predictor for FFS (P=0.006, Figure 2D). At the last follow-up, twelve of the 135 responders relapsed after IST, meanwhile eight patients in responders and seven patients in non-responders experienced clonal evolution after IST, corresponding to cumulative incidences at 5.2% of relapse and 6.5% of evolution, which were obviously lower than previous reports. Conclusions: The combination of rATG and CSA was confirmed as an effective first-line therapy for children with SAA/VSAA in our cohort. We discerned a protracted recovery but an ultimately comparable long-term outcome of rATG. Baseline blood parameters (ANC, ALC, ARC) were predictive factors of response rate. Intensive supportive care may be necessarily pivotal to survival in cases of VSAA. Importantly, moderate PNH clone might be beneficial to FFS. Besides, for those who experienced gradually progressed disease course, early HSCT might be a more preferable option than receiving IST although further validation remains to be done. Figure 1 Overall efficacy at different time points following IST initiation Figure 1. Overall efficacy at different time points following IST initiation Figure 2 Prognostic factors for overall survival (OS) and failure-free survival (FFS) Figure 2. Prognostic factors for overall survival (OS) and failure-free survival (FFS) Disclosures No relevant conflicts of interest to declare.

Overall survival benefit with masitinib mesylate in imatinib-naive, locally advanced, or metastatic gastrointestinal stromal tumor (GIST): 4-years follow-up of the French Sarcoma Group phase II trial.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 85-85 ◽  
Author(s):  
J. Blay ◽  
A. Le Cesne ◽  
N. Bin Bui ◽  
O. Bouche ◽  
A. Adenis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Locally Advanced ◽  
Phase Iii ◽  
Long Term Results ◽  
First Line ◽  
Juxtamembrane Region ◽  
Metastatic Gist

85 Background: Masitinib is a novel tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib (IM) against both wild-type KIT receptor and its mutated form in the juxtamembrane region (IC 50=100 nM versus 200 nM for IM, 3 nM versus 27nM and 40 nM versus 120nM, respectively, for exons 9,11, and 13). This multicenter phase II study evaluated efficacy and safety of masitinib as a first-line treatment of advanced GIST. Methods: IM-naïve patients with inoperable, locally advanced or metastatic GIST received oral masitinib (7.5 mg/kg/day) until progression, refusal or toxicity. Efficacy variables included response rate, best response (RECIST), progression-free survival (PFS) and overall survival (OS). Initial results were previously reported in EJC 2010. We present here the same series with updated PFS and OS (median follow up of 48 months). Results: 30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. At the cut-off date (31 august 2010), 9 patients are still under treatment with a median treatment duration of 41 months (min=33, max=52). Two additional progressions have been reported for a total of 14 events (13 progressions and 1 death). Updated median PFS is 41 months (95% CI: [17.5; NR]) with PFS rates of 60% [39; 77], 56% [35; 73] and 45% [24; 64] respectively at 2, 3 and 4 years. With 8 patients dead, median OS is not yet reached with OS rates of 90% [72; 97], 87% [68; 95] and 74% [52; 87], respectively, at 2, 3, and 4 years. The main frequent relevant grade 3 toxicities were: rash (10%), neutropenia (7%) and abdominal pain (7%) with one patient presented a grade 4 skin exfoliation. No other relevant long-term toxicities were reported and no more patients discontinued treatment due to suspected toxicity. Conclusions: The long term results observed with masitinib confirm a very interesting activity with prolonged PFS and OS. These results support the head to head comparison with imatinib in the currently ongoing phase III randomized clinical trial in first line locally advanced or metastatic GIST patients. [Table: see text]

scholarly journals Mesenchymal Stem Cell Therapy in Decompensated Liver Cirrhosis: A Long-Term Follow-up Analysis of the Randomized Controlled Clinical Trial

2021 ◽  
Author(s):  
Ming Shi ◽  
Yuan-Yuan Li ◽  
Ruo-Nan Xu ◽  
Fan-Ping Meng ◽  
Shuang-Jie Yu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Liver Function ◽  
Treated Group ◽  
Control Group ◽  
Overall Survival Rate ◽  
Decompensated Liver Cirrhosis ◽  
Randomized Controlled

Abstract BackgroundMesenchymal stem cells (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC), however, whether the medication can improve outcome of these patients is poorly understand.MethodsThis prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n=111) and umbilical cord-derived MSC (UC-MSC) treated group (n=108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survial rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated.ResultsDuring the follow-up check period from 13th to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group.ConclusionsTherapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.

HHV-8-Negative, Idiopathic Multicentric Castleman Disease (iMCD): A Description of Clinical Features and Therapeutic Options through a Systematic Literature Review

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4861-4861 ◽  
Author(s):  
David C Fajgenbaum ◽  
Amy Liu ◽  
Jason Ruth ◽  
Chris Nabel ◽  
Brian Finkelman ◽  
...  
Keyword(s):  
Case Reports ◽  
Castleman Disease ◽  
Hiv Positive ◽  
Inclusion Criteria ◽  
First Line ◽  
Median Length ◽  
Advisory Committees ◽  
Multicentric Castleman Disease ◽  
Hiv Negative

Abstract Background: Multicentric Castleman disease (MCD) describes a heterogeneous group of poorly-understood diseases involving proinflammatory hypercytokinemia that ultimately results in systemic inflammatory symptoms, generalized lymphadenopathy, multiple organ system dysfunction, and even death. HHV-8 is responsible for driving MCD in immunosuppressed patients (HHV-8-associated MCD). There is also a cohort of HHV-8-negative MCD cases, referred to as idiopathic MCD (iMCD), in which the etiology remains unknown. No formal diagnostic criteria exist for iMCD, and knowledge is limited to small case series and case reports. Objectives: We conducted a systematic literature review to describe demographic, clinical, and laboratory features of iMCD as well as the treatments currently used in practice. Methods: PubMed was queried using a comprehensive list of terms to identify all published cases of HHV-8-negative MCD. Criteria for study inclusion were as follows: (1) Pathology-confirmed Castleman disease in multiple lymph nodes; (2) Exclusion of another cause of Castleman-like histopathology, such as SLE or POEMS syndrome; (3) Negative testing for HHV-8 via PCR of blood, PCR of lymph node tissue, serum serologies, and/or IHC for LANA-1; (4) Written in English and published from January 1995 to July 2013; and (5) Availability of specified minimum data elements. HIV-positive cases were excluded. Inclusion criteria were confirmed by three independent investigators, who also extracted data into a standardized database. Case report authors were contacted to gather additional data in a standardized case report form. Results: 3,428 articles were identified on PubMed. Initial evaluation for exclusion criteria yielded 1,951 MCD cases; 629 patients were HIV-positive (32%). Of the 999 HIV-negative and 323 HIV-unknown MCD cases, 626 were HHV-8 negative (32% of total MCD), 517 were HHV-8-unknown (26%), and 179 were HHV-8-positive (9%).129 cases of HHV-8-negative MCD met all inclusion criteria and were included in the final analysis. 58% were male and median age was 50 years (range: 2-80). Frequently reported clinical features included: fever (51/64), enlarged liver and/or spleen (45/60), pleural effusion (29/38), edema (26/36), and weight loss (21/29). There were 43 plasmacytic, 26 mixed, and 23 hyaline vascular cases out of 108 cases that reported histopathological subtype. The most commonly reported laboratory abnormalities included elevated CRP (70/79), anemia (76/90), hypergammaglobulinemia (63/82), hypoalbuminemia (57/63), elevated IL-6 (57/63), and positive ANA (14/38). Of cases with abnormal platelet levels, 28 had thrombocytopenia and 14 had thrombocytosis. There were 19 reported cases with elevated soluble IL-2R levels and 15 with elevated VEGF. 27 patients were diagnosed with a malignancy before (5), concurrently with (12), or after (10) diagnosis. Most commonly employed first line therapies included corticosteroid monotherapy (36%), combinations of cytotoxic chemotherapies (36%) that included regimens with cytoxan (17%) and rituxan (12%), and anti-IL-6 therapies, such as siltuximab and tocilizumab, without a cytotoxic agent (10%). Thalidomide, bortezomib, anakinra, and IVIG were used less frequently. Patients experienced no response (21%), partial response (42%), and complete response (37%) to first-line therapies. Failure (relapse, death, additional treatment) of first line therapy occurred in 41% of patients, and median time to treatment failure was 6 months. Overall, 22% of patients died by the time of most recent follow up (median: 28 months) with median length of survival among fatal cases being 26 months (range: 1-120). The most common causes of death were septic shock, multi-organ failure, including renal and cardiac, pulmonary complications, and malignancy. Conclusion: This study identified a significant proportion of MCD patients who are HIV-negative and HHV-8-negative (iMCD). 45% of patients did not demonstrate the plasmacytic variant alone, which has been classically associated with MCD. It is striking that 22% of patients died by the time of most recent follow up, which had a median length of 26 months. Despite the many limitations of analyzing case reports, this study provides the most comprehensive data on HHV-8-negative MCD to date. A global natural history study and Castleman disease registry are urgently needed to gather more extensive data on MCD. Disclosures Fajgenbaum: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Cyclophosphamide, rituximab, tocilizumab, thalidomide, bortezomib, anakinra, and intravenous immunoglobulin will be presented as drugs used in HHV-8-negative MCD. It is very important to inventory the treatments that a physician has available when conventional therapies do not work, which is frequent in MCD. At the time that this data set was assembled, there were no FDA approved therapies for this orphan disease. van Rhee:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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