scholarly journals Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up

2018 ◽  
Vol 36 (33) ◽  
pp. 3315-3323 ◽  
Author(s):  
Sandra Lockmer ◽  
Bjørn Østenstad ◽  
Hans Hagberg ◽  
Harald Holte ◽  
Ann-Sofie Johansson ◽  
...  
Keyword(s):  
Optimal Timing ◽  
Indolent Lymphoma ◽  
First Line ◽  
Term Outcome ◽  
Cross Sectional ◽  
Term Survival ◽  
Long Term Outcome ◽  
New Therapy

Purpose For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies. Methods Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m2, and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations. Results At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%. Conclusion Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.

Long Term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Beta Thalassemia Major

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4606-4606
Author(s):  
Fouzia NA ◽  
Sindhuvi E ◽  
Kavitha ML ◽  
Korula A ◽  
Abraham A ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Endocrine Disorders ◽  
Term Outcome ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome

Abstract Introduction:Allogeneic hematopoietic stem cell transplantation (HSCT) cures beta thalassemia major (TM). Such individuals, ex-thalassemics, have good long term survival. However, there is limited data on long term outcome (LTO) of this therapy. This is particularly relevant as these patients often have organ dysfunction pre-transplant due to secondary hemosiderosis apart from the impact of post-transplant factors such as chronic GVHD, chimerism status and iron depletion therapy (IDT). In this report, we describe the LTO of patients with TM who underwent HSCT with busulfan (Bu) and cyclophosphamide (Cy) conditioning at our center from 2000 to 2011 and had a minimum of 2 year follow-up. Method: Data was extracted from prospectively maintained standardized case record forms for details of HSCT and long term follow-up with particular reference to GVHD, chimerism (evaluated at day +30, +60, +100 and thereafter as indicated), IDT (initiated at variable periods post-HSCT) and metabolic and endocrine disorders evaluated on physician discretion or as per clinical indications. Results:A total of 190 patients underwent matched related donor HSCT from 2001 to 2011 with Bu/Cy based conditioning. After excluding those who expired or had primary graft failure or did not have at least 2 years of follow-up, 124 patients were available for analysis of LTO. 44 patients (35.5%) class 3, 69 patients (55.6%) class 2 and 11 patients (8.9%) class 1. The median age was 7 years (range: 2-24) with 81 males (65.3%). The median follow-up was 7 years (range: 2 to 14). Chronic GVHD was present in 22 patients (17.7%]. Mixed chimerism (MC) occurred in 40 patients (32%) in the first year after HSCT: level I in 21 (52.5%), level II in 10 (25%), level III in 7 (17.5%), and level unknown in 2(5%). At last follow-up, 20/40 (50%) patients with MC went on to CC, 18 maintained stable MC (level I-5, level II-9 and level III-4) with hemoglobin of 11.35g/dl (range: 9-13.5), while 2 (5%) with level 3 MC remained transfusion dependent. Median serum ferritin (SF) at HSCT was 2367 ng/ml (range: 685-7660). IDT was initiated in 90 (72.6%) patients at a median of 15 months (range: 6-53) post-HSCT - 13 patients (14.4%) were treated with phlebotomy alone, while 39 (43.3%) received chelation and 38 (42.2%) the combination. Reduction in SF/month [absolute quantity (ng/ml/month) and percent] was as follows: 40.5 (range: 11.68 - 125.78); 1.67% (range: 0.5-4.58), 54.9 (range: 9.3- 278.7); 2.1% (range: 0.41- 13.8) and 36.6 (range: 3.51-590.7); 1.3% (range: 0.42-42.99), in the phlebotomy, chelation and combination groups, (p=0.077 & 0.017, respectively). SF level of <300 ng/ml was achieved in 33 patients (31%) at last follow-up. Anthropometry measurements (at last follow up) revealed short stature in 53 patients (42.7%; 38M/15F), underweight in 32 patients (25.8%; 20M/12F) and overweight in 14 (11.3%) patients (11M/3F). A total 48 patients (38.7%) had the following endocrine disorders: hypogonadism in 33 (73.3%), primary hypothyroidism in 9 (18.8%), hypopituitarism in 4 (8.3%), diabetes mellitus in 3 (6.2%), and hypoparathyroidism, dyslipidemia and hypertension in 1 patients each. 40 patients were vitamin D deficient (83.3%). Endocrine complications were more common in female patients (55.8% versus 29.6%; p=0.006). Two patients (1.3%) developed malignancies at 7 and 8 years, post-HSCT. Among different patient, donor and graft characteristics, there were no predictors of MC, nor did the ferritin levels or chelation therapy post-HSCT affect the incidence of endocrine complications in this cohort. Conclusion: Our data shows that even though the long term survival of ex-thalassemics is extremely good, at least 40% of them suffer from several co-morbidities related to iron overload and various metabolic and endocrine disorders which requires a coordinated plan for their management. The aim therefore should be to transplant these patients as early as possible before such complications occur and implement IDT intensively early after HSCT. Disclosures No relevant conflicts of interest to declare.

Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery

1995 ◽  
Vol 83 (4) ◽  
pp. 583-589 ◽  
Author(s):  
Leslie N. Sutton ◽  
Patricia T. Molloy ◽  
Heidi Sernyak ◽  
Joel Goldwein ◽  
Peter L. Phillips ◽  
...  
Keyword(s):  
Radical Surgery ◽  
Conservative Surgery ◽  
Low Grade ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Content Type ◽  
Fine Print

✓ The feasibility of radical surgery for astrocytomas of the optic chiasm/hypothalamus has been reported by several groups. Such surgery carries significant risks, however, including permanent damage to the pituitary gland, optic apparatus, hypothalamic structures, and carotid arteries. The benefits of radical surgery, both in terms of efficacy and toxicity, should, therefore, be evaluated against standard therapy, as is usually done for new chemotherapeutic protocols. To this end, a retrospective review was performed of 33 patients treated at Children's Hospital of Philadelphia between 1976 and 1991 who met criteria that would have made them eligible for radical surgery in many centers today, but were treated with either no surgery or conservative surgery (< 50% resection) or biopsy followed by adjuvant therapy with local radiation therapy (29 patients) and/or chemotherapy with actinomycin-D and vincristine (18 patients). The review encompassed all children with a globular enhancing mass of at least 2 cm in the hypothalamic/chiasmatic region, no evidence of optic nerve involvement or involvement of the optic radiations by computerized tomography or magnetic resonance imaging, and follow up of at least 3 years. All but one patient had tissue confirmation of a low-grade or pilocytic astrocytoma. Thirteen of the patients were 2 years of age or younger at diagnosis. Five individuals died: three of tumor progression, one of acute shunt malfunction, and one of intercurrent infection. The remaining 28 were alive at last follow up, a mean of 10.9 years from diagnosis. Twenty-three surviving patients have functional vision in at least one eye, 12 require no endocrine replacement, and 16 are in or have completed schooling with regular academic requirements. If radical surgery is to become standard care for children with low-grade astrocytomas of the hypothalamic/chiasmatic region, long-term survival and functional outcome will have to equal or surpass those of historical controls who were treated conservatively.

Surgical resection of pulmonary inflammatory pseudotumors: long-term outcome

2017 ◽  
Vol 25 (6) ◽  
pp. 440-445 ◽  
Author(s):  
Marine Peretti ◽  
Dana M Radu ◽  
Karel Pfeuty ◽  
Antoine Dujon ◽  
Marc Riquet ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Survival Rates ◽  
R0 Resection ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Long Term Survival ◽  
Inflammatory Pseudotumors

Background Pulmonary inflammatory pseudotumors are rare lesions that remain problematic in several aspects, especially regarding the therapeutic strategy. The goal of this study was to evaluate long-term survival in a multicenter series of patients who required surgery for pulmonary inflammatory pseudotumors. Methods Thirty-six cases of pulmonary inflammatory pseudotumors, operated on in 3 French thoracic surgery departments between 1989 and 2015, were studied retrospectively. We recorded pre-, peri- and postoperative data for each patient, and long-term survival was analyzed. Results There were 22 men and 14 women. Mean age was 53.5 years (range 14–81 years). Three pneumonectomies, 1 bilobectomy, 19 lobectomies, 2 segmentectomies, 10 wedge resections, and 1 biopsy were performed. Complete resection was carried out in 32 (88.8%) patients. Median follow-up was 76 months. Five-year and 10-year survival rates were respectively 86.8% and 81.7% (96% and 90% for patients with R0 resection). Conclusions Long-term survival was excellent for patients with pulmonary inflammatory pseudotumors who benefited from surgery, especially when surgical resection was complete. These results confirm that surgical resection must be proposed as the first-line treatment for patients with pulmonary inflammatory pseudotumors.

Long-term outcome in patients with juvenile dermatomyositis: a cross-sectional follow-up study

2011 ◽  
Vol 41 (1) ◽  
pp. 50-58 ◽  
Author(s):  
P Mathiesen ◽  
H Hegaard ◽  
T Herlin ◽  
M Zak ◽  
FK Pedersen ◽  
...  
Keyword(s):  
Juvenile Dermatomyositis ◽  
Term Outcome ◽  
Cross Sectional ◽  
Long Term Outcome ◽  
Follow Up Study

Aortic Valve–Sparing Root Replacement (David I Procedure) in Adolescents: Long-Term Outcome

2019 ◽  
Author(s):  
Erik Beckmann ◽  
Andreas Martens ◽  
Heike Krueger ◽  
Wilhelm Korte ◽  
Tim Kaufeld ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Connective Tissue Diseases ◽  
Young Patients ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Initial Surgery ◽  
Valve Sparing

Introduction Aortic valve-sparing root replacement (David's procedure) is an especially appealing treatment option for young patients. Here, we present the short-, mid, and long-term outcomes of this operation in adolescent patients. Methods Between September 1994 and March 2014, 29 patients aged 6 to 21 years underwent the David-I procedure at our center. We conducted a retrospective study with follow-up. Results The mean age was 16.8 ± 3.4 years and 90% (n = 26) were male. Marfan's syndrome was present in 86% (n = 25) of cases. Ninety-seven percent (n = 28) of cases were performed electively, and one case (3%) was performed emergently for acute aortic dissection type A. There were no early perioperative deaths (0%). Follow-up, which was completed on 100% of patients, comprised a total of 394 patient years and a mean follow-up time of 13.6 ± 5.4 years. The estimates for survival at 1, 5, and 10 years after initial surgery were 100, 97, and 93%, respectively. During follow-up, there were four (14%) late deaths and five (17%) aortic valve-related reoperations. The 1-, 5-, and 10-year estimates for freedom from valve-related reoperation were 100, 86, and 83%, respectively. The perioperative mortality for these five reoperations was 0%. Discussion Aortic valve–sparing root replacement can be performed in adolescents with a very low perioperative risk. Long-term survival seems to be affected by connective tissue diseases.

xxx

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8123-8123
Author(s):  
C. Tarella ◽  
M. Zanni ◽  
A. Rambaldi ◽  
F. Benedetti ◽  
R. Passera ◽  
...  
Keyword(s):  
Complete Remission ◽  
High Dose ◽  
Low Grade ◽  
High Grade ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Long Term Survival

8123 Background: The high-dose sequential (HDS) chemotherapy approach, including early dose-intensification and autograft with peripheral blood progenitor cells (PBPC), was introduced several years ago (Gianni & Bonadonna, 1989); subsequently, it has been broadly used in the management of both non-Hodgkin s (NHL) and Hodgkin s Lymphoma (HL). The outcome of a large series of lymphoma patients treated with the HDS approach at 10 GITIL Centers is reported. Methods: Data have been collected on 1,266 patients, who received either the original or slightly modified HDS regimens. There were 213 HL and 1,053 NHL (630 intermediate/high-grade, 423 low-grade); median age was 46 yrs. Overall, 671 (53%) patients had refractory/relapsed disease, 595 (47%) were at diagnosis. Most patients were autografted with PBPC; 158 (12%) patients did not undergo autografting due to toxicity, disease progression or poor harvests. Results: Overall, 1,013 (80%) patients reached Complete Remission (CR) following HDS. As to December 2006, 93 (7%) patients died for early/late toxicities, 328 (26%) died for lymphoma, 844 are known to be alive. At a lead follow-up of 18 years, and a median follow-up of 5 yrs, the 5-yr Overall Survival (OS) projection is 64% (S.E.: 2%). The long-term survival was quite favorable in patients achieving a Complete Remission (CR), with a 5-yr OS projection of 76%. The prolonged OS in patients achieving CR was consistent in all lymphoma subtypes, i.e. both low and high-grade NHL (5-yr OS: 77% in both), and HL (5-yr OS: 72%). Patients at diagnosis had a significantly better outcome compared to patients treated for relapsed/refractory disease, again CR achievement was associated with prolonged survival in both subgroups (82% and 69%, respectively, at 5 yrs.). On multivariate Cox survival analysis, CR achievement was the most powerful predictor of long-term survival (HR 0.13, c.i.: 0.10–0.17). Lastly, achieving substantial tumor reduction before autografting had a major influence on the clinical outcome. Conclusions: 1. the HDS program is feasible in a multicenter setting; 2. the long-term outcome is well influenced by the CR status after HDS; 3. the influence of CR achievement on the long-term survival holds true in all lymphoma subtypes, including indolent lymphomas; 4. an adequate pre-autograft tumor debulking may contribute to a favorable long-term outcome. [Table: see text]

scholarly journals Long-Term Outcome of Liver Transplantation in HIV-1-Positive Patients: 15-Year Follow-Up

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Shinji Yamamoto ◽  
Robert Schwarcz ◽  
Ola Weiland ◽  
Antti Oksanen ◽  
Annika Wernerson ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Highly Active Antiretroviral Therapy ◽  
Patient Survival ◽  
Biliary Cirrhosis ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Hiv 1

Liver transplantation (LT) for patients with human immunodeficiency virus type-1 (HIV-1) infection has been associated with poor outcome. However, after the introduction of the highly active antiretroviral therapy, short-term patient survival after LT has improved significantly. We examined the long-term outcome of HIV-1-positive patients who underwent LT. Medical records were analysed in nine HIV-1-positive LT patients who underwent LT from August 1998 to May 2012. Eight were known to be HIV-1 positive at the time of listing for LT and had end-stage liver disease (ESLD) due to hepatitis C. One patient had primary biliary cirrhosis, and primary HIV-1 infection was found at the date of LT. Seven of the nine patients remain alive to date. So far, three have survived more than 12 years after LT. The overall patient survival rate for both five and 10 years is 77.8%. Four patients experienced acute rejection and six acquired biopsy-confirmed HCV recurrence. HIV-1 replication was effectively blocked during follow-up in all patients. We conclude that long-term survival of HIV-1-positive patients after LT can be achieved. Our study suggests that LT can offer an effective treatment option in selected HIV-1 infected patients with ESLD.

scholarly journals Long-term survival in Waldenstrom macroglobulinemia: 10-year follow-up of Southwest Oncology Group–directed intergroup trial S9003

Blood ◽  
2009 ◽  
Vol 113 (4) ◽  
pp. 793-796 ◽  
Author(s):  
Madhav V. Dhodapkar ◽  
Antje Hoering ◽  
Morie A. Gertz ◽  
Saul Rivkin ◽  
Jackie Szymonifka ◽  
...  
Keyword(s):  
Prognostic Models ◽  
International Prognostic Scoring System ◽  
Serum Lactate Dehydrogenase ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia

AbstractThe survival of patients with Waldenstrom macroglobulinemia (WM) varies enormously. The development of prognostic models in WM has been fraught by limited follow-up in current studies. Here, we update the outcome of a prospective WM trial with a median follow-up of 10 years for live patients. Of the 59 previously untreated patients who initially were observed, only 12 patients (21%) required therapy at a median follow-up of 100 months. Multivariate analysis among the 183 patients requiring therapy reaffirmed age 70 years or greater, previous nonprotocol therapy, and β-2 microglobulin (B2M) of 3 mg/dL or greater as prognostic factors. Importantly, increased serum lactate dehydrogenase (LDH) was identified as an additional independent variable, which improved risk assessment beyond the recent WM international prognostic scoring system (ISSWM). By using age, previous therapy, B2M, and LDH, we identified 3 risk groups with 8-year survival estimates of 55%, 33%, and 5% (P < .001). These data provide novel insights into factors predicting long-term outcome in WM. This trial has been registered with www.cancer.gov under ID 4852904.

Long-Term Outcome for De Novo Lymphoblastic Lymphoma (LL) After Frontline Therapy with Hyper-CVAD Regimen and Variants.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2831-2831
Author(s):  
Deborah A. Thomas ◽  
Stefan Faderl ◽  
Susan O'Brien ◽  
William G. Wierda ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
First Line ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cns Disease ◽  
Mediastinal Disease

Abstract Abstract 2831 The long-term outcome for newly diagnosed LL has improved with use of intensive chemotherapy regimens designed for acute lymphoblastic leukemia (ALL) when compared to the historical experience with modified NHL regimens. An early report established the hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high dose methotrexate (MTX) and cytarabine) as an effective first line therapy for LL [Thomas D, Blood 104:1624, 2004]. From April 1992 to March 2009, 49 patients (pts) with de novo LL were treated with hyper-CVAD (n=20) or modified hyper-CVAD regimens (n=11 anthracycline intensification with liposomal daunorubicin-ara-C for course 2 [regimen detailed in Thomas D, Cancer, e-pub], n=18 without anthracycline intensification). CNS prophylaxis alternated intrathecal MTX and ara-C on days 2 and 7 of the first 4 courses in the absence of CNS disease. Bulky (> 7 cm) mediastinal disease at presentation was an indication for consolidative XRT (after consolidation prior to maintenance therapy). POMP (6-mercaptopurine, vincristine, MTX, prednisone) maintenance therapy was administered for 24 months with standard hyper-CVAD (MTX-L-asparaginase intensifications mos 7 & 11); and extended to 30 mos with the modified hyper-CVAD regimens (hyper-CVAD followed by MTX-L-asparaginase mos 6 & 7 and 18 & 19). Allogeneic stem cell transplant (SCT) was performed in first complete remission (CR) only if inadequate response to therapy. Median age was 31 yrs (range, 17–59); 77% were males. Mediastinal disease was noted in 74%; 30% were associated with pericardial and/or pleural effusions. Two pts had superior vena cava syndrome and five had CNS disease. T-lineage disease was present in majority (79%). Eight (17%) pts had bone marrow involvement. Overall CR rate was 96% in 46 evaluable patients (3 in CR at start), with remainder achieving partial response (PET scan negative residual mediastinal disease not qualifying for CR). Of the 23 pts with bulky mediastinal disease at presentation, 74% underwent XRT as planned. With a median follow-up of 80 months (range 30–187+ months), 31 (66%) pts remained alive without disease. Overall 5-yr rates for CR duration and survival were 72% and 68%, respectively. Fourteen pts relapsed or progressed within a median of 13 months (6 with standard, 8 with modified hyper-CVAD); five pts were successfully salvaged with chemotherapy and allogeneic SCT. The hyper-CVAD is a highly active regimen for de novo LL with long-term follow-up confirming the earlier report. Early anthracycline intensification was clearly not beneficial. The treatment paradigm for LL has recently changed owing to availability of new agents and data supporting superior efficacy of pediatric regimens compared with conventional adult regimens. For older adults with de novo LL, the deoxyguanosine analog nelarabine has now been incorporated into the hyper-CVAD regimen as a single agent during consolidation (cycles 9 & 10) and maintenance (in lieu of the early intensifications) [Vigil CE, ASCO 2010, abstract 6524], whereas adolescents and younger adults are treated according to the pediatric-inspired augmented Berlin-Frankfurt-Muenster regimen. An augmented hyper-CVAD regimen (dose intensifying VCR/dexamethasone components and incorporating pegylated asparaginase) has been successfully piloted in the salvage setting. The optimal first line chemotherapy of LL continues to be refined; the role of autologous or allogeneic SCT for LL in first CR remains unclear since majority of patients can be cured without use of these modalities. Disclosures: Off Label Use: Nelarabine for de novo T-lymphoblastic leukemia/lymphoma Nelarabine for de novo T-lymphoblastic leukemia/lymphoma.

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.

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