scholarly journals Acquired Aplastic Anemia Patients Using Single Agent Cyclosporine a, in Resource Poor Setting

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4312-4312
Author(s):  
Liri Seraj ◽  
Alma Cili ◽  
Adela Perolla ◽  
Polikron Pulluqi ◽  
Elsuarta Çalliku ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Treatment Response ◽  
Cyclosporine A ◽  
Single Agent ◽  
Supportive Therapy ◽  
Severe Aplastic Anemia ◽  
Resource Poor Setting ◽  
First Year ◽  
Hematopoietic Stem ◽  
Resource Poor

Abstract Abstract: Aplastic Anemia (AA) is a syndrome characterized by peripheral blood pancytopenia and bone marrow hypo-cellularity. Acquired AA is considered to have an underlying autoimmune etiology. Hematopoietic stem cell transplantation (HSCT) still remains the treatment of choice for AA patients. However, due to cost restrictions, cyclosporine A has been tried in resource poor setting as a single agent. Aim: The aim of this study is to observe the single agent Cyclosporine treatment response in AA patients. Materials and Methods: The following study is a retrospective study. Patients diagnosed for the first time between January 2010 and December 2020, aged 14 years old and up, treated with cyclosporine A and supportive therapy, were included in this study. Statistical analysis for this study was performed using SPSS. All subjects were started on 5mg/kg per day of cyclosporine. The patients were divided into three groups according to the IAASG classification criteria (Non severe AA, Severe AA and Very severe AA). Another subgroup analysis related to sex (females to males) and age was performed, classifying the patients into three subgroups (14-29; 30-59; 60+ years old). Overall Survival (OS) was evaluated using Kaplan-Meier method with Log-Rank test. Overall survival (OS) was defined as the duration from the first day of treatment to all-cause death. T-test and Chi-square test were used for categorical and continuous parameters analysis. P value lower than 0.05 was considered statistically significant. Results: A total of 35 patients were diagnosed as Acquired Aplastic Anemia between 2010-2020. The median age at diagnosis was 51 years old. The incidence of Aplastic Anemia in Albania is 1.35 per million inhabitants. 5 patients (19.2%) developed complete response. NSAA showed the best treatment response (38.5%). The relation between the treatment response at the end of the first year of cyclosporine treatment and the 5-year survival was statistically significant, Pearsons' correlation coefficient 0.441 (P=0.035). The estimated mean survival time of AA patients in our study is 68.6 months. When compared the survival to the severity, the SAA group showed a better OS (53 months) (P=0.081). The 5-year cumulative survival of the patients resulted 71.9%. VSAA group had the worst estimated survival (45.5%). The youngest age group showed the worst 5-year survival on cyclosporine alone (33.3%) (P=0.016). The subgroup analysis between males and females resulted in women having a slightly better survival than men, 59 and 58 months respectively (P=0.276). Those patients who failed the treatment with cyclosporine alone at the end of the first year, showed the worse 5-year survival (50%). Conclusions: This study emphasizes once again the importance of the IAASG classification on AA patients' prognosis and treatment outcome. The youngest patients should be considered for HSCT rather than be treated on cyclosporine alone. Treatment on cyclosporine alone and supportive therapy is a reasonable option for older patients in poor resource countries as Albania. Abbreviations: AA- Aplastic Anemia, NSAA- Non severe aplastic anemia, SAA- Severe aplastic anemia, VSAA- Very severe aplastic anemia, HSCT- Hematopoietic stem cell transplantation, IAASG-International Aplastic Anemia Study Group, SPSS-Statistical Package for the Social Sciences. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effective treatment with tacrolimus for patients with non-severe aplastic anemia refractory/ intolerant to cyclosporine A: a retrospective study

2020 ◽  
Author(s):  
Yali Du ◽  
Yuzhou Huang ◽  
Wenzhe Zhou ◽  
Xinjian Liu ◽  
Fangfei Chen ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Cyclosporine A ◽  
Complete Response ◽  
Treg Cells ◽  
Severe Aplastic Anemia ◽  
Hematopoietic Stem ◽  
Independent Risk Factors ◽  
Elevated Creatinine ◽  
One Year

Abstract Background: For the symptomatic non-severe aplastic anemia (NSAA) patients who cannot afford anti-thymocyte globulin (ATG) or allogeneic hematopoietic stem cell transplantation (HSCT), tacrolimus (FK) was occasionally reported to be an option if they were not response or tolerant to the cyclosporine A (CsA). Method: We collected and analyzed respectively 101 NSAA patients refractory or intolerant to CsA with no chance of HSCT or ATG, and treated them with tacrolimus for at least 6 months and followed up for at least one year. Results: The overall response (ORR) was 38.6% (complete response: 9.9%; partial response: 28.7%) and the median time to optimal response was 6 (3～10) months. 32 (31.7%) cases had elevated creatinine level. 8 (7.9%) cases had elevation of AST/ALT. 25.6% (10/39) of patients relapsed at the end of follow-up. Age (P=0.0005), FK concentration (4.0~12ng/ml, P=0.0005) and intolerance to CsA (P=0.012) were the independent risk factors for ORR. Treg cells level pre-FK treatment was much lower than healthy controls (3.7±0.6% vs 6.8±0.7%, P=0.0004), but increased significantly after FK treatment (3.7±0.6% vs. 7.1±0.8%, P=0.0039). Conclusion: Our data provide a possibility of tacrolimus as a salvage treatment for patients with NSAA refractory or intolerant to CsA.

Eltrombopag Can Stimulate Trilineage Hematopoiesis In Patients with Refractory Severe Aplastic Anemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4427-4427
Author(s):  
Matthew J. Olnes ◽  
Yong Tang ◽  
Susan Soto ◽  
Elaine M Sloand ◽  
Philip Scheinberg ◽  
...  
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Aplastic Anemia ◽  
Severe Aplastic Anemia ◽  
Successful Outcome ◽  
Severe Thrombocytopenia ◽  
Hematopoietic Stem ◽  
Platelet Counts ◽  
Transfusion Independence

Abstract Abstract 4427 Severe aplastic anemia (SAA) is characterized by trilineage marrow hypoplasia and a paucity of hematopoietic stem cell progenitors. SAA is treated with immunosuppression or allogeneic stem cell transplantation (SCT), with a successful outcome in a majority. However, 20–40% of patients without a suitable donor for SCT do not respond to immunosuppression and may have persistent severe thrombocytopenia. Thrombopoietin (TPO) is the principal regulator of platelet production, and it exerts its effects through binding the megakaryocyte progenitor TPO receptor mpl, which stimulates production of mature megakaryocytes and platelets. Eltrombopag, a small molecule TPO mimetic that binds to mpl, increases platelet counts in healthy subjects, and in patients with chronic immune thrombocytopenic purpura. Both TPO and eltrombopag stimulate more primitive multilineage progenitors and stem cells in vitro. Patients with SAA and thrombocytopenia have very elevated TPO levels; nevertheless, we asked whether pharmacologic doses of eltrombopag could stimulate hematopoiesis in these patients without other options. We are conducting a pilot phase II study of eltrombopag in SAA patients with severe thrombocytopenia refractory to immunosuppressive therapy. Consecutive eligible adult patients were treated with oral eltrombopag at an initial dose of 50 mg daily, with escalation to a maximum dose 150 mg daily, with the goal of maintaining a platelet count of >20,000/uL above baseline. Treatment response was measured after three months and was defined as platelet count increases to 20,000/uL above baseline, or stable platelet counts with transfusion-independence for a minimum of 8 weeks. Nine patients have been enrolled and six are evaluable for response to date. Two patients did not respond to treatment. Three patients achieved platelet responses by 12 weeks of treatment, and all have sustained their responses (median follow up 10 months). Four patients exhibited improved hemoglobin levels 12 weeks after starting treatment (median hemoglobin increase of 2.1 g/dL) and two patients who were previously dependent on packed red blood cell transfusions have achieved transfusion-independence. Three neutropenic patients exhibited increased neutrophil counts after treatment with eltrombopag (median increase 0.46K cells/uL). These results provide evidence that eltrombopag can improve platelet counts in patients with severe refractory thrombocytopenia, and perhaps more surprisingly, have a clinically relevant impact on erythropoiesis and myelopoiesis. Updated data will be presented at the Society's meeting. Disclosures: Off Label Use: Eltrombopag for thrombocytopenia in refractory severe aplastic anemia patients.

Successful Engraftment In Children With Severe Aplastic Anemia After Transplantation Of HLA-Identical Hematopoietic Donor Cells With Shorter Telomere Length

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2047-2047
Author(s):  
Abdulrahman Alsultan ◽  
Gabriela M. Baerlocher ◽  
Elisabeth Oppliger Leibundgut ◽  
Sameera AlAfghani ◽  
Reem Al-Sudairy ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Telomere Length ◽  
Graft Failure ◽  
Reference Range ◽  
Severe Aplastic Anemia ◽  
Hematopoietic Stem ◽  
Cell Dose ◽  
Gvhd Prophylaxis ◽  
Donor Cells

Abstract Telomere length measurement is recommended in donors of patients with severe aplastic anemia (SAA) to screen for silent inherited telomeropathy. This was based on prior reports of delayed engraftment and graft failure after hematopoietic stem cell transplantation (HSCT) when donors had short telomeres or were silent carriers of dyskeratosis congenita (DC)-causative mutations (Fogarty et al. Lancet 2003 and Awaya et al. Biol Blood Marrow Transplant. 2002). The challenging question is, in the absence of a known causative mutation, how short the donor’s telomere length could be to be labeled as not suitable. Here, we summarize our patients with SAA who have been transplanted with HLA-matched related hematopoietic donor cells that were of variable telomere length. A total of eight patients were transplanted using the following conditioning in 6 patients (cases 2, 4, 5, 6 in table, and two with undetermined telomere length) that included fludarabine (35mg/m2) on day -6 to -2, cyclophosphamide (40mg/kg) on day -6 and -5, and rabbit antithymocyte globulin (thymoglobulin) (2.5mg/kg) on day -5 to -2. GVHD prophylaxis was mycophenolate mofetil and cyclosporine (CSA). Two patients (cases 1 and 3) had cyclophosphamide (50mg/kg) on day -5 to -2 and thymoglobulin (2.5mg/kg) on day -4 to -2 with CSA and methotrexate or steroids as GVHD prophylaxis. All eight patients (5 females and 3 males) with an average age of 7 (range 0.8-13.3 years) had bone marrow failure as a predominate feature and except for one patient (case 4) who had short stature, mental retardation and a brain MRI with bilateral encephalomalacia there were no abnormal physical findings, specifically no classical features of DC i.e. nail dystrophy, leukoplakia, and skin pigmentation. All donors had normal physical examination and normal CBC. History of consanguinity was reported in all patients except one. Patients had normal chromosomal fragility test, but the telomere length values for six of the patients and their donors were in the lower reference range of healthy Caucasian individuals (Table). Three patients had very short telomeres in practically all lymphocytes subsets (cases 3, 4, and 6) similar to the pattern observed in patients with DC. The telomere length results of the six donors were variable (table). One donor had very short telomeres (case 3) in all lymphocyte subsets. The telomere length result was not available for this donor prior to commencing conditioning, however, CD34 cell dose infused was adequate (9.29 X106/kg recipient weight). Genetic tests are ongoing to identify causative mutations. One patient with undetermined telomere length had a heterozygous mutation in the TINF2 gene that was not present in his donor. All eight patients engrafted successfully, median time to neutrophil engraftment was 22 (range, 11-29 days) and platelet engraftment 30 (range, 15-62 days). Median infused nucleated cell dose was 2.8 (range, 1.6-6.5 X108/kg) and CD34 cell dose was 5.8 (range, 1.1-11.2 X106/kg). Median donor chimerism was 100% for myeloid cells and 62% for T cells around 100 days post HSCT. None of our patients had acute GVHD and one patient had mild classic chronic GVHD of the skin. All patients are alive with median follow-up duration of 377 days (range, 152-907 days). In conclusion, fludarabine-based conditioning using reduced dose cyclophosphamide (80mg/kg) seems safe and feasible in our SAA patients with shorter telomeres. Hematopoietic stem cells obtained from related donors with shorter telomeres successfully rescued patients with SAA without signs of graft failure over a median follow-up of 377 days. It is not clear yet, whether these patients and donors have an inherited telomeropathy or whether the reference range of telomere lengths established from Caucasians is also applicable for Arabs or other ethnic groups as this could possibly exclude donors unnecessarily. These studies are ongoing and an update will be presented. Disclosures: No relevant conflicts of interest to declare.

More Intensity Immuno-Suppression In Conditioning Regimen  may Favor Donor Stem Cell Sustained Engraftment In Allogeneic Stem Cell Transplantation For Acquired Severe Aplastic Anemia Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5452-5452
Author(s):  
Sun Can ◽  
Lin Xia ◽  
Huang Yuxian ◽  
Chen Tuzhen ◽  
Bingyi Wu
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Hematopoietic Stem ◽  
Acquired Severe Aplastic Anemia

Abstract Background Hematopoietic stem cell transplantation (HSCT) is the first-line therapy for patients younger less than 40 years old with severe aplastic anemia (SAA). And the long-term survival for patients with SAA who received HSCT reaches to 70%-90%. Cyclophosphamide-based conditioning regimen with or without antithymocyte globulin (ATG) has been adopted in majority of HSCT for SAA patients with HLA matched related donor. However the graft rejection and graft failure in HSCT for SAA with cyclophosphamide-based conditioning regimen is still as high as 5%-16%. The aim of this study is to explore whether more immue suppression in conditioning regimen could favor the donor stem cells sustained engraftment for severe aplastic anemia patients receiving allogeneic hematopoietic stem cell transplantation. Fludarabine and busulfan were added in cyclophosphamide-based conditioning regimen to intensity immune suppression in conditioning. Methods To analyze the outcomes and chimeras of 40 patients with SAA who received HLA matched allo-HSCT from 2000 to 2012 with either fludarabine-based conditioning regimen or cyclophosphamide-based conditioning regimen retrospectively and to explore the relationship between the chimeras and conditioning regimen. Results Forty patients with SAA who received HLA matched allo-HSCT From May, 2000 to Dec. 2012. Twelve patients ( median age 25 year old  range 13-52, male 7, femal 5) received  fludarabine-based conditioning regimen which composed of fludarabine (30 mg/m2/d ×5d), busulfan ( 3 mg/kg ×2d ), cyclophosphamide ( 60mg/kg/d×2d) and ATG (2.5mg/kg/d ×5d). Twenty patients( median age 23 year old  range 12-42, male 19, femal 9)  received  cyclophosphamide-based conditioning regimen which composed of cyclophosphamide (50mg/kg/d ×4d )and ATG (2.5mg/kg/d ×2d ). The  median dose of MNC were 4.5×108/kg (range 3.8-7.0×108/kg )and 3.58×108/kg (range 3.2-6.8×108/kg ) and CD34+ cells were  4.5×108/kg and 3.58×108/kg respectively. GVHD prophylaxis were cyclosporine and short-term course methotrexate. Donor chimera was detected on day+30, +90, +180, and 360 after HSCT by short tandem repeat polymerase chain reaction, or fluorescein in situ hybridization for X and Y chromosomes in cases when patients and donors were sex mismatched. Results All patients with fludarabine-based conditioning regimen were successful Hematopoietic reconstitution and no graft failure occurred in this group patients. But two patients could not get recovery in cyclophosphamid-based conditioning regimen group. And complete donor chimeras always present when chimeras were detected by STR-PCR or FISH at day 30,day 60, day 90 and d 180 post transplantation in fludarabine-based conditioning regimen group, while seven patients with cyclophosphamide-based conditioning regimen were mixed chimeras at day 30 post transplant.  The graft was rejected in six of the seven patients at day 90 post transplant in cyclophosphamide-based conditioning regimen group. The complete donor chimera in fludarabine-based conditioning regimen group was obvious higher than that in cyclophosphamide-based conditioning regimen group ( p=0.037). The incidence of aGVHD in the fludarabine group was 16.7% and 10.7% in the cyclophosphamide-based group. There is no significant difference of aGVHD between two group (P = 0.627). The incidence of cGVHD was 8.3% and 10.7% respectively. The bacterial infections developed in 16.7% and 28.6% of patients respectively (P=0.693), The overall survival were 83.33% and 82.14% in fludarabine-based conditioning regimen group and cyclophosphamide-based group respectively (p=0.870). Conclusions More intensity immuno-suppression in conditioning regimen may favor donor stem cell sustained engraftment in allogeneic stem cell transplantation for acquired severe aplastic anemia patients. Disclosures: No relevant conflicts of interest to declare.

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