A Retrospective Hospital Based Study of 440 Patients of Aplastic Anemia from India: Epidemiology; Response to Therapy; and Possible Significance of Jaundice during Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5299-5299 ◽  
Author(s):  
Rajat Kumar ◽  
Dharma R. Choudhary ◽  
Manoranjan Mahapatra ◽  
Atul Kotwal ◽  
Alka Mathur ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Statistical Significance ◽  
Medical Science ◽  
Specific Treatment ◽  
Complete Response ◽  
Response To Therapy ◽  
Acute Leukemias ◽  
Overall Response ◽  
High Incidence

Abstract All new cases of aplastic anemia (AA) seen in the Hematology out patient department (OPD) of All India Institute of Medical Science (AIIMS) from January 2001 to December 2003 were studied till last follow up. Complete response (CR) was defined as - normalization of blood counts; Partial response (PR) as - improvement in blood counts, transfusion independence and not meeting criteria of CR. Database was created in MS Access and SPSS ver 11 was used for statistical analysis. Descriptive statistics were calculated and appropriate tests of significance carried out. Result- A total of 440 cases of AA were seen during the study period. The total number of new hematology patients seen in the same period was 8605; thus AA comprised 51.13 per thousand (95% CI, 37.9–67.1) new hematology cases. The number of acute leukemias (AML and ALL) diagnosed during this period was 392: the ratio of AA to acute leukemia was 1.1:1. The total number of OPD patients registered in AIIMS for these 3 years was 43,04,849. Thus AA patients comprised 102.23 per million (95% CI, 83.2–123.8) hospital OPD patients. This very high incidence of AA may be due to the tertiary nature of AIIMS. The median age at presentation was 19yr (range 2–84), with males 311 (71%) and females 129 (29%). At presentation the hematological values were: mean hemoglobin (Hb) 5.2 ± 2.03 g/dl; mean total leucocyte count (TLC) 3.1 ± 1.3 x 109/L, mean platelet counts 33.8 ± 19.5 x 109/L. Follow up period was for a median of 3 months (range 0–42). Specific treatment consisted of (a) Androgens - Stanozolol at 2 mg/kg/d (b) Cyclosporine at 3mg/kg/d (c) Antithymocyte globulin at total dose of 75–80mg/kg over 5 to 8 days and (d) combinations of these drugs. The following subgroups were excluded from analysis (i) 14 (3.1%) patients whose records were incomplete and (ii) 38 (8.6%) patients who received only supportive therapy with no response, but whose individual follow up was limited. The overall response to all therapies was 29.7%. The response to different subgroups and statistical significance is given in Table. Jaundice occurred in 23 (5.2%) patients during treatment and HBsAg was positive in two. The course of jaundice was clinically uncomplicated and lasted for 2 to 3 weeks. An interesting finding was a partial or complete response to therapy in 19/23 (82.6%) with CR in 47.8% and PR in 34.8%. The difference in response rate of those who developed jaundice while on therapy and those who did not was statistically significant (P=0.000). Conclusions: The high incidence of AA in India provides a potential for future studies regarding its etiopathogenesis and therapy. Economic limitations make Stanozolol an important drug in developing countries with its response rates of 19.7%. The unexpected high response in those who developed jaundice during therapy suggests that this could be a marker for recovery. Response§ to Different Therapies in 388 Patients of Aplastic Anemia Treatment group Androgen alone Cyclosporin alone Androgen and Cyclosporin ATG + Cyclosporin ±Androgen Test Chi square test. ©Not statistically significant. ®Statistically significant. §Response compared to overall response to other therapies. Total number (%) 172 (39.1) 13 (3) 179 (40.7) 24 (6.3) Overall response, % 19.7 8.3 31.2 62.5 PR, % 8.6 8.3 15.9 33.3 CR, % 11.1 0 15.3 29.2 P value 0.067© not done 0.083© 0.000®

scholarly journals Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3115-3121 ◽  
Author(s):  
Bart Barlogie ◽  
Mauricio Pineda-Roman ◽  
Frits van Rhee ◽  
Jeff Haessler ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Complete Remission ◽  
Statistical Significance ◽  
Complete Response ◽  
Free Survival ◽  
Cytogenetic Abnormalities ◽  
Prognostic Feature ◽  
Total Therapy ◽  
Initiation Of Therapy ◽  
The One

AbstractTotal Therapy 2 examined the clinical benefit of adding thalidomide up-front to a tandem transplant regimen for newly diagnosed patients with multiple myeloma. When initially reported with a median follow-up of 42 months, complete response rate and event-free survival were superior among the 323 patients randomized to thalidomide, whereas overall survival was indistinguishable from that of the 345 patients treated on the control arm. With further follow-up currently at a median of 72 months, survival plots segregated 5 years after initiation of therapy in favor of thalidomide (P = .09), reaching statistical significance for the one third of patients exhibiting cytogenetic abnormalities (CAs; P = .02), a well-recognized adverse prognostic feature. The duration of complete remission was also superior in the cohort presenting with CAs such that, at 7 years from onset of complete remission, 45% remained relapse-free as opposed to 20% on the control arm (P = .05). These observations were confirmed when examined by multivariate analysis demonstrating that thalidomide reduced the hazard of death by 41% among patients with CA-positive disease (P = .008). Because two thirds of patients without CAs have remained alive at 7 years, the presently emerging separation in favor of thalidomide may eventually reach statistical significance as well.

Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.

1997 ◽  
Vol 15 (7) ◽  
pp. 2553-2558 ◽  
Author(s):  
H Xiao ◽  
M Mazumdar ◽  
D F Bajorin ◽  
M Sarosdy ◽  
V Vlamis ◽  
...  
Keyword(s):  
Germ Cell ◽  
Salvage Therapy ◽  
Germ Cell Tumors ◽  
Complete Response ◽  
Response To Therapy ◽  
Survival Status ◽  
Long Term Follow Up ◽  
Time To Relapse ◽  
Good Risk

PURPOSE To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP). PATIENTS AND METHODS Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported. RESULTS One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years. CONCLUSION Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.

Response to Therapy with Imatinib Mesylate in Patients with CML Is Poor in Non-Caucasian Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2937-2937
Author(s):  
Sarah George ◽  
Laura Horvath ◽  
Robert Molokie ◽  
John Berry ◽  
Damiano Rondelli ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Response Rates ◽  
Complete Response ◽  
Response To Therapy ◽  
Low Risk ◽  
Risk Scores ◽  
Genetic Characteristics

Abstract Imatinib mesylate is a targeted therapy for chronic myeloid leukemia (CML). All phases of CML are susceptible to imatinib, with more durable responses occurring in patients in chronic phase. Studies in patients with chronic phase CML who have been treated with imatinib have shown a complete hematologic remission (CHR) rate of 97%, a complete cytogenetic remission (CCR) rate of 70%, and a complete molecular remission (CMR) rate of 10%. Racial and ethnic differences have not been extensively studied in relation to cancer outcomes, and no studies to date have demonstrated a difference in outcomes based upon race or ethnicity of patients with CML treated with imatinib. Methods : A retrospective chart review of patients with CML who have been treated with imatinib at the University of Illinois, the Westside VA, and MacNeal hospitals over the past 3 years was performed. Primary endpoints were rates of CHR, CCR, and CMR in Caucasian (C) and non-Caucasian (NC) patients with CML on treatment with imatinib. A secondary endpoint was the correlation of Sokal scores at initiation of imatinib with rates of CHR, CCR, and CMR. Results: 26 charts were reviewed of 7 C and 19 NC patients ( 12 African American, 5 Latino, 1 Indian, 1 Lebanese) in chronic phase CML. For C patients at the initiation of imatinib, mean age was 46 (45 for NC) and mean Sokal score was 0.79 (0.75 for NC). 32% (8/25) of patients had cytogenetic abnormalities in addition to the Philadelphia chromosome, all of whom were NC (50% were pretreated; 29% obtained CCR). Mean duration from diagnosis to treatment with imatinib was 5 months for C and 9 months for NC. Mean length of follow up while on imatinib was 28 months for C and 14 months for NC, with early termination due to lack of follow up, progression of disease, and death. 31% (8/26) of patients (25% C, 75% NC) had received prior treatments with agents such as IFN, AraC, busulfan, anagrelide, homoharrington, and allogeneic SCT. 100% of pretreated C had CCR (vs 33% of pretreated NC). CHR rate was 100% in C (4/4) vs. 87.5% (14/16) in NC. CCR was obtained in 100% of C (6/6) but only 14% (2/14) of NC. CMR rate was noted to be 33% (1/3) in Caucasians compared to 8.3% (1/12) in NC. Low risk Sokal scores were associated with CHR rate of 100% in C (3/3) and 75% (6/8) in NC, as well as CCR rate of 100% in C (5/5) and only 25% (2/8) in NC. Conclusions: NC patients have a poorer response to treatment with imatinib for CML. The discrepancy between complete response rates (most notably the CCR rate) between C and NC patients could be accounted for by differences in the genetic characteristics of the disease, metabolism, or adherence rates. NC patients with low risk Sokal scores also had poorer complete response rates than C patients with the same risk scores. Prospective studies are needed to further evaluate these differences and discern their etiology. Given poor CCR rates, NC patients should be HLA typed soon after diagnosis and considered for transplant if a matched donor is available.

Rituximab in the Treatment of Adults with Chronic Idiopathic Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3930-3930 ◽  
Author(s):  
Ghassan Zalzaleh ◽  
Ahmad Jajeh ◽  
Diemante Tamoseviciene
Keyword(s):  
Partial Response ◽  
Hemolytic Anemia ◽  
Complete Response ◽  
Pure Red Cell Aplasia ◽  
Lymphocytic Leukemia ◽  
Overall Response ◽  
Medical Centers ◽  
History Of ◽  
Refractory Itp

Abstract Corticosteroids have been the first line of treatment of ITP since 1950, however some patients do not respond to this treatment (refractory) and some will relapse after its discontinuation. For such patients second line treatments were introduced. Some patients will continue to be refractory to this treatment and need other therapy modality. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen exposing B Lymphocytes, causing its depletion. This could alter the production of auto-antibodies in some Auto-Immune diseases and thus could be used in their treatment. Few medical centers had reported using Rituximab in the treatment of refractory (ITP) and (AIHA), yet its definite role could not be determined, and here we share our experience. Patients with documented diagnosis of ITP or AIHA who were refractory to at least two lines of therapy including steroids were offered to receive Rituximab (375mg/m2 weekly for 4 weeks). 15 patients were enrolled, 10 with ITP, 4 with AIHA, 1 with Coombs negative Hemolytic anemia, and 1 with pure red cell aplasia. One had both ITP and AIHA. 10 were females and 5 males. 5 were >60 years old and 10 were < 60 years old. 2 out of the 10 patients with ITP had also Chronic Lymphocytic Leukemia (CLL). Duration of follow up ranged from 2 months to 17 months (average 7 mos). Of the 10 patients with refractory ITP treated with Rituximab overall response was 60%. 4 were NR (no response), 2 were MR (minimal response: Platelets increased to <50000), 2 were PR (Partial response: Platelets increased to <100000) and 2 were complete response (Platelets became normal). 3 patients of 6 with Hemolytic anemia or PRC aplasia had NR, 1 had MR (Hct <30), and 2 had partial response (Hct 30–35). No complete response was observed in this group. In 3 patients with hemolytic anemia and CLL 1 had MR, 1 had PR and 1 had NR. 2 patients with hemolytic anemia who had NR died as a complication of their disease (one with septic shock and one with severe autoimmune flare up). Only one patient with refractory ITP had mild allergic side effects and did not complete 4 doses. No Rituximab related mortality was observed. CONCLUSION: Rituximab therapy had a variable but valuable effect in the treatment of patients with chronic refractory ITP and refractory/ relapsed AIHA. Overall response in our group reached 60%. No clinical or laboratory parameters were found to predict response, although there was a suggestion that males, younger age, and no history of splenectomy have a better chance of response. As we lack an effective alternative treatment in chronic refractory ITP and AIHA, Rituximab use could be a valid option in view of its mild toxicity. Further follow up of our patients and input from other institutions in this regard are needed.

Evaluation of number of target lesions to analyze in time to progression by RECIST

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6549-6549
Author(s):  
M. Gonen ◽  
L. Schwartz ◽  
R. Ford
Keyword(s):  
Response Assessment ◽  
Optimal Number ◽  
Response To Therapy ◽  
Phase Iii ◽  
Time To Progression ◽  
Overall Response ◽  
Considerable Controversy ◽  
Set Up

6549 Background: RECIST criteria were designed to evaluated tumor shrinkage and response to therapy by measurement of multiple target lesions, evaluation of non target and new lesions. There is considerable controversy surrounding the optimal number of lesions to assess response, with RECIST requiring the measurement of up to 10 target lesions. These guidelines were set up to evaluate the endpoint of best overall response. Increasingly, time to progression has become an important endpoint in oncology trials. We evaluated the optimal number of lesions to measure to accurately and reproducibly assess time to progression. Methods: We evaluated target lesions metastases in 105 patients enrolled on a Phase III clinical trial. All patients underwent CT at baseline and standard follow up scans until progression. Target lesions were measured unidimensionally and response was assessed according to RECIST by 2 independent Radiologists. A total of 519 target lesions were assessed. Response was calculated according to the rules of target lesions (up to 10) by RECIST, utilizing the 2 largest lesions and randomly selecting 2 target lesions. Results: Using the 2 largest lesions, time to progression was concordant in 83% of cases. The 2 Radiologists determined the two same largest lesions in 89% of cases. Since the determination of the largest or the same target lesions is not always possible or performed, a random selection of 2 target lesions demonstrated a 76% concordance in the time to progression. Conclusions: Measurement of time to progression may have a greater degree of variability than measurement of best overall response and therefore measurement of minimal selected lesions will lead to a great variability in response assessment. No significant financial relationships to disclose.

NONISOCENTRIC RADIOSURGICAL RHIZOTOMY FOR TRIGEMINAL NEURALGIA

Neurosurgery ◽  
2009 ◽  
Vol 64 (suppl_2) ◽  
pp. A84-A90 ◽  
Author(s):  
John R. Adler ◽  
Regina Bower ◽  
Gaurav Gupta ◽  
Michael Lim ◽  
Allen Efron ◽  
...  
Keyword(s):  
Pain Relief ◽  
Trigeminal Neuralgia ◽  
Symptom Relief ◽  
Complete Response ◽  
Patient Reported ◽  
High Incidence ◽  
Facial Numbness ◽  
Prescription Dose ◽  
Trigeminal Root

Abstract OBJECTIVE Although stereotactic radiosurgery is an established procedure for treating trigeminal neuralgia (TN), the likelihood of a prompt and durable complete response is not assured. Moreover, the incidence of facial numbness remains a challenge. To address these limitations, a new, more anatomic radiosurgical procedure was developed that uses the CyberKnife (Accuray, Inc., Sunnyvale, CA) to lesion an elongated segment of the retrogasserian cisternal portion of the trigeminal sensory root. Because the initial experience with this approach resulted in an unacceptably high incidence of facial numbness, a gradual dose and volume de-escalation was performed over several years. In this single-institution prospective study, we evaluated clinical outcomes in a group of TN patients who underwent lesioning with seemingly optimized nonisocentric radiosurgical parameters. METHODS Forty-six patients with intractable idiopathic TN were treated between January 2005 and June 2007. Eligible patients were either poor surgical candidates or had failed previous microvascular decompression or destructive procedures. During a single radiosurgical session, a 6-mm segment of the affected nerve was treated with a mean marginal prescription dose of 58.3 Gy and a mean maximal dose of 73.5 Gy. Monthly neurosurgical follow-up was performed until the patient became pain-free. Longer-term follow-up was performed both in the clinic and over the telephone. Outcomes were graded as excellent (pain-free and off medication), good (&gt;90% improvement while still on medication), fair (50–90% improvement), or poor (no change or worse). Facial numbness was assessed using the Barrow Neurological Institute Facial Numbness Scale score. RESULTS Symptoms disappeared completely in 39 patients (85%) after a mean latency of 5.2 weeks. In most of these patients, pain relief began within the first week. TN recurred in a single patient after a pain-free interval of 7 months; all symptoms abated after a second radiosurgical procedure. Four additional patients underwent a repeat rhizotomy after failing to respond adequately to the first operation. After a mean follow-up period of 14.7 months, patient-reported outcomes were excellent in 33 patients (72%), good in 11 patients (24%), and poor/no improvement in 2 patients (4%). Significant ipsilateral facial numbness (Grade III on the Barrow Neurological Institute Scale) was reported in 7 patients (15%). CONCLUSION Optimized nonisocentric CyberKnife parameters for TN treatment resulted in high rates of pain relief and a more acceptable incidence of facial numbness than reported previously. Longer follow-up periods will be required to establish whether or not the durability of symptom relief after lesioning an elongated segment of the trigeminal root is superior to isocentric radiosurgical rhizotomy.

scholarly journals Efficacy and Safety of Eltrombopag with or without Immunosuppressant in Patients with Relapsed/Refractory Acquired Aplastic Anemia: A Real-World Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1124-1124
Author(s):  
Jiang Ji ◽  
Ziqi Wan ◽  
Jing Ruan ◽  
Yali Du ◽  
Miao Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Aplastic Anemia ◽  
Median Time ◽  
Relapse Rate ◽  
Real World ◽  
Reticulocyte Count ◽  
Efficacy And Safety ◽  
Overall Response ◽  
Significant Difference

Abstract Background: Eltrombopag (EPAG) with or without immunosuppressant (IST) has been applied in acquired aplastic anemia (AA), yet data of EPAG+IST in relapsed/refractory AA was limited, and no study has compared efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients. Aims: To evaluate and compare the efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients in a real-world setting. Methods: Data from patients diagnosed as acquired AA in our center were retrospectively collected. All the enrolled patients were refractory/relapsed to the standard IST for at least 6 months before EPAG. All patients had been treated with EPAG, which was started at 25 mg/day and increased every 2 weeks to a maximum of 150 mg/day until a best response was achieved. Meanwhile, some patients were treated with cyclosporin A (CsA) or tacrolimus (FK506) at the same time. EPAG had to be prescribed for at least 6 months before evaluation. Complete response (CR), overall response (OR) and relapse rate, as well as adverse events and factors which could affect efficacy were analyzed. Results: Totally 99 patients (83 non-severe AA (NSAA) and 16 SAA) were included in the study. The median age at EPAG initiation was 46 (13-88) years old, the median time of EPAG treatment was 11 (6-41) months and the median time of follow-up was 18 (6-41) months. 72 patients were treated with EPAG+IST, including 41 (56.9%) treated with EPAG+FK506 and 31 (43.1%) treated with EPAG+CsA. 27 patients were treated with EPAG alone. No significant difference was found between EPAG+IST group and EPAG group in patient baseline characteristics like age, male proportion, NSAA proportion, presence of PNH clone, proportion of previous ATG+CsA / CsA treatment, previous IST duration and dosage. With compatible follow-up time, EPAG exposure duration and dosage, there was no significant difference in OR/CR rate at 3 rd/6 th/12 th month between patients who was treated with EPAG+FK506 and EPAG+CsA. Under similar compatible baseline conditions, the OR rate was 33.3% vs 22.2% (P=0.284) at 3 rd month, 61.1% vs 37.0% (P=0.032) at 6 th month, and 67.2% vs 42.1% (P=0.051) at 12 th month for patients treated with EPAG+IST and EPAG alone, respectively, but no significant difference was found in time to response (3 (1-12) vs 3 (1-7) months, P=0.679) or CR rate at 3 rd/6 th/12 th month (6.9%/12.5%/20.7% vs 3.7%/7.4%/5.3%, P&gt;0.05) between the two groups. Relapse occurred at 6 th to 12 th month of EPAG treatment, and the relapse rate at 12 th month was 9.8% and 27.3% (P=0.154) for patients treated with EPAG+IST and EPAG alone, respectively. For patients treated with EPAG+IST, responders had a significantly higher baseline reticulocyte count (60.25 (11.5-230.5)×10 9/L vs 16.7 (6.6-56.6)×10 9/L, P=0.040) compared with non-responders. No predictive factors for the overall response were found for patients treated with EPAG alone. Adverse events which led to dosage regulation were gastrointestinal disorders (2.8% vs 3.7%, P=1.000), elevated creatinine (2.8% vs 0, P=0.599), elevated ALT (1.4% vs 0, P=1.000) and arthralgia (0 vs 3.7%, P=0.280) for patients with EPAG+IST and EPAG, respectively. No deaths were found in either group, while the clone evolution rate was 2.8% and 3.7% (P=1.000) in EPAG+IST and EPAG monotherapy group, respectively. Conclusion: EPAG+IST had higher OR rate than EPAG monotherapy with similar side effects for patients with relapsed/refractory acquired AA. Those with higher baseline reticulocyte count were more likely to respond to EPAG+IST. Key words: relapsed/refractory, aplastic anemia, eltrombopag, immunosuppressant, efficacy Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: In the presented study, eltrombopag was prescribed in relapsed/refractory aplastic anemia patients.

scholarly journals Real-World Effectiveness and Safety of Eltrombopag in Patients with Aplastic Anemia: A Chinese Nationwide Survey

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5020-5020
Author(s):  
Wenrui Yang ◽  
Bing Han ◽  
Hong Chang ◽  
Bingyi Wu ◽  
Fankai Meng ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Real World ◽  
Overall Response Rate ◽  
Response Rate ◽  
Line Treatment ◽  
First Line ◽  
Overall Response ◽  
Treatment Naïve ◽  
First Line Treatment

Immunosuppressive therapy (IST) based on antithymoglobin (ATG) and cyclosporin (CsA) is the first-line treatment for severe aplastic anemia (SAA) patients who are unfit for transplantation,and the overall response rate (ORR) is about 70%.The utility of eltrombopag (EPAG),a TPO receptor agonist, achieved robust hematologic response in refractory and treatment-naïve SAA patients in clinical trials and some other studies. However, only a few data came from Asia countries where higher incidence of AA has been reported. A retrospective study on the use of EPAG in AA was conducted in mainland China. Aplastic anemia (transfusion dependent non-severe, severe, and very severe) patients who started eltrombopag before Feb 2019 and continued for at least 3 months either as first-line treatment or as rescue treatment, were enrolled. The maximum daily dosage of EPAG used continuously for at least 2 weeks is defined as the stable dosage. Response criteria were referred to that used in previous reports (Townsley DM, NEJM 2017; BCSH, BJH 2016). Fifty-six patients from eleven centers were enrolled in this study, including 26 males and 30 females at the median age of 39 (7-80) years. All patients were transfusion-dependent by the time of EPAG administration, and there were 14 VSAA, 24 SAA and 18 transfusion dependent non-severe aplastic anemia (TD-NSAA). Nineteen treatment-naïve patients received EPAG and IST (ATG+CsA, n=10; CsA/CsA+androgen, n=9) as first-line treatment. Thirty-seven patients were refractory to IST. Eltrombopag was administered at a median dose of 75 (25-150) mg per day for 7 (3-31) month. The median follow-up time was 9 (3-40) months. The overall response rate in patients receiving EPAG as first-line therapy was 78.9% (15/19), and most patients achieved complete response (CR) (10/15). Among the 10 patients receiving ATG+CsA, 6 patients achieved hematologic response (HR) at 3 months post-treatment, including 3 CR. Six patients were diagnosed as VSAA and three achieved HR. For the 9 patients treated with CsA/CsA+androgen, 8 achieved HR (88.9%) and 4 were CR (44.4%) at 3 months. By last follow-up, the cumulative HR rate was 70% in ATG+CsA group and 89% in CsA/CsA+ androgen group. Among the 14 responders, 11 patients receiving EPAG at a stable dosage ≤75mg/d and achieved HR at 3 months. The overall response rate in IST-refractory patients was 46% (17/37), with trilineage response in 27% patients at 3 months. For the 18 ATG+CsA refractory SAA patients,trilineage HR occurred in 4 patients (22.2%, 4/18), bi-lineage HR in one patient and single lineage HR in one patient. Thus, the total HR was 33.3% (6/18) at 3 months and increased to 44% (8/18) by last follow-up. Among the 19 CsA/CsA+ androgen refractory patients, 6 (31.5%, 6/19) achieved trilineage HR, one achieved bi-lineage HR and 4 achieved single lineage response. Total HR rate was 57.9% (11/19) at 3 months after EPAG initiation and 68% (13/19) by last follow-up, including 9 patients with trilineage HR. Among 17 responders, 13 received a stable EPAG dose of≤75mg/d. Most patients tolerated EPAG well. Adverse events occurred in 29 patients (52%) and most were mild to moderate, including gastrointestinal symptom (n=15, e.g. abdominal pain, nausea), impaired liver function (n=5), skin changes (n=7, e.g. skin pruritus and rash) and musculoskeletal pain (n=6), and venous thrombus (n=2). Eltrombopag dosage was reduced in 2 patients due to severe digestive symptoms at 100 mg/d and discontinued in one patient who suffered from upper limb venous thrombus. In conclusion, EPAG is effective and safe in treating Chinese AA patients at a daily dose of 75mg and less. The real-world result of EPAG in Chinese patients is similar to those reported in Western countries. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Retrospective Multicenter Case Study Evaluating the Characteristics, Management and Outcome of Acquired Amegakaryocytic Thrombocytopenia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3167-3167
Author(s):  
Anais Roeser ◽  
Guillaume Moulis ◽  
Mikael Ebbo ◽  
Louis Terriou ◽  
Elsa Poullot ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Aplastic Anemia ◽  
Board Of Directors ◽  
Bone Marrow Biopsy ◽  
Research Funding ◽  
Advisory Committees ◽  
Overall Response ◽  
Acquired Amegakaryocytic Thrombocytopenia

Abstract Introduction Acquired amegakaryocytic thrombocytopenia (AAT) is an extremely rare disease characterized by acquired megakaryocytic aplasia or hypoplasia with no other lineage abnormalities. Given limited evidence, the first aim of this study was to describe the characteristics, management and outcome of patients with AAT, the second aim was to examine the therapeutic response through a systematic review of published case reports. Patients and Methods We carried out a retrospective multicenter study through the French Reference Network for Adult Autoimmune Cytopenias, including patients aged &gt; 18 years with acquired thrombocytopenia with a platelet count &lt; 50 x 10 9/L, associated with a megakaryocytes / granulocytes ratio &lt; 50 % on bone marrow, diagnosed from July 2007 to February 2020. Exclusion criteria were: abnormal granular lineage, evidence of dysplasia, bone marrow infiltration by tumor cells or hematologic malignancy, significant karyotype abnormality, and significant paroxysmal nocturnal hemoglobinuria clone. Bone marrow biopsy were centrally reviewed. Patients' medical charts were collected using the standardized form of the referral center for adult immune thrombocytopenia (ITP). Response to treatment was defined according to standardized international criteria for ITP: response (R) and complete response (CR) were respectively defined as platelet count of &gt; 30 × 10 9/L with at least a doubling of the baseline value, and platelet count of &gt; 100 × 10 9/L ; overall response as either R or CR. We performed a systematic review conducted through Medline and Scopus databases from 1970 to April 2021. Cases were included in the analysis if initial platelet count was &lt; 50 x 10 9/L and bone marrow examination was available, demonstrating a megakaryocyte hypoplasia or aplasia with no alternate diagnosis. Results We screened 23 patients reported as thrombocytopenia with absence or decreased megakaryocytes. Eleven patients were excluded because of: presence of megakaryocytes on bone marrow biopsy despite megakaryocytic aplasia on bone marrow aspirate (n=2), absence of bone marrow biopsy (n=4), aplastic or hypoplastic bone marrow (n=3), moderate thrombocytopenia &gt; 50 x 10 9/L (n=1), lack of data (n=1). Twelve patients were included in the analysis. AAT patients had a median age of 52.5 years, 5/12 (41.7%) were female, 6/12 (50%) had a preexisting autoimmune disease (Table 1). All bone marrow biopsies reviewed to date contained CD8+ T-cell infiltrates. Eight patients received a first line treatment with corticosteroids and/or intravenous immunoglobulins (IVIg), a single response was observed. Ten patients received cyclosporine in monotherapy resulting in 4CR, and 1R or in combination with diverse agents with heterogenous responses. Six had received a single therapy with thrombopoietin receptor agonists (TPO-RAs) inducing 4 CR. Eventually, 9 patients (75%) achieved a CR under therapy, obtained with ciclosporin alone in 3 cases, ciclosporin in association with TPO-RA or ATG in 2 cases, cyclophosphamide followed-up by mycophenolate mofetil in 1 case, and TPO-RAs alone in 4 patients (of whom 3 had previously received at least on immunosuppressive therapy). After a median follow up time of 4.0 years (range 1.2 - 11.9), 2 (16%) patients eventually developed an aplastic anemia, 7 and 41.5 months respectively after initial AAT diagnosis. The literature search yielded 108 articles, of which 75 articles reporting 85 cases were included in the final analysis. The pooled analysis of newly reported and historic cases included 97 cases. Overall response rates to corticosteroids and IVIg were respectively 22.4 % and 5.3 % (Table 2). Ciclosporin was used as single agent in 37.1 % of patients, with an overall response rate of 66.7 %. TPO-RAs were used in 9 cases, with a CR in 7 patients (77.8%). Overall, 9/97 patients (9.3 %) experienced an aplastic anemia during the follow-up. The presence of a thymoma was associated with a higher risk of aplastic anemia (OR 6.83 (95%CI 1.22-34.00, p=0.020)). Conclusion Distinguishing AAT from ITP is of significance as the outcome and response to therapy strongly differ. Aplastic anemia may occur in the follow-up but remain rare. Corticosteroids and IVIg are inefficient in most cases, ciclosporin appear to be very effective, TPO-RA could also be an option, as single therapy or in associations. Further data will be needed to define the respective place of these treatments. Figure 1 Figure 1. Disclosures Moulis: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenix: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees. Ebbo: Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Other: Attendance Grant; Amgen: Honoraria; Sobi: Other: Attendance Grant; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Haioun: Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Miltenyi: Honoraria, Research Funding. Michel: Amgen,Novartis,UCB,Argenx,Rigel: Honoraria. Godeau: Amgen: Consultancy; Novartis: Consultancy; Grifols: Consultancy; Sobi: Consultancy. Mahevas: GSK: Research Funding; Amgen: Honoraria.

scholarly journals Low-Dose Radiotherapy Versus Moderate-Dose Radiotherapy for the Treatment of Indolent Orbital Adnexal Lymphomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Jonathan Baron ◽  
Christopher M. Wright ◽  
Daniel Y. Lee ◽  
Maribel Carpenter ◽  
Shwetha H. Manjunath ◽  
...  
Keyword(s):  
Low Dose ◽  
Response Rates ◽  
Complete Response ◽  
Moderate Dose ◽  
Exact Test ◽  
Overall Response ◽  
Low Dose Radiotherapy ◽  
Kaplan Meier ◽  
Grade 3

PurposeRadiation therapy (RT) with doses ranging from 24 Gray (Gy) to 40 Gy is a proven treatment modality for indolent orbital adnexal lymphoma (IOAL), but recently the use of low dose RT (LDRT, defined as 2 Gy x 2 fractions) has become a notable alternative. However, limited data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose 4 – 36 Gy). We present a single institution retrospective analysis comparing outcomes of patients with IOALs following LDRT or MDRT.MethodsA total of 36 patients treated with 38 consecutive courses of RT were identified; LDRT was delivered for 14 courses and MDRT for 24 courses. Overall response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Local control (LC), orbital control (OC), and overall survival (OS) rates were estimated with the Kaplan-Meier method. RT toxicity was graded per CTCAEv5 and compared with the Fisher’s exact test.ResultsMedian follow-up time was 29 months (m) (range, 4-129m), and median MDRT dose used was 24 Gy (range 21-36 Gy). Overall response rates (ORR) were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. OS at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively (p=0.36). LC rates at 2 years was 100% for both LDRT and MDRT groups and at 4 years was 100% and 89% for the LDRT and MDRT groups, respectively (p=0.56). The 4-year OC rate (including both ipsilateral and contralateral relapses) was 80% and 85% for the LDRT and MDRT groups, respectively (p=0.79). No patient required treatment with RT to a previously irradiated orbit. Acute toxicities were reported following 6 LDRT courses compared to 20 MDRT courses (p=.014). No Grade 3 or higher acute toxicities occurred in either group. Late toxicities were reported following 2 LDRT courses compared to 10 MDRT courses (p=0.147).ConclusionsLDRT produced similar ORR, LC, OC, and OS rates compared to MDRT with fewer acute and minimal late toxicities reported. Future multi-center studies with larger patient numbers are warranted to show significant associations.

Sign in / Sign up

Export Citation Format

Share Document