scholarly journals THROMBOTIC MICROANGIOPATHY IN HAEMATOPOIETIC CELL TRANSPLANTATION:AN UPDATE

2010 ◽  
Vol 2 (3) ◽  
pp. e2010033 ◽  
Author(s):  
Evi Stavrou ◽  
Hillard Michael Lazarus
Keyword(s):  
Thrombotic Microangiopathy ◽  
Hematopoietic Cell Transplantation ◽  
Immunosuppressive Agents ◽  
Treatment Strategies ◽  
Calcineurin Inhibitors ◽  
Cell Integrity ◽  
Medication Exposure ◽  
Conditioning Regimens ◽  
Treatment Mortality ◽  
General Plasma

Allogeneic hematopoietic cell transplantation (HCT) represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA). In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases), patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD) disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents.  Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended.   

scholarly journals Targeted Treatment and Survival Following Relapse after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia and MDS in the Contemporary Era

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4567-4567
Author(s):  
Sanghee Hong ◽  
Lisa Rybicki ◽  
Donna Corrigan ◽  
Betty K. Hamilton ◽  
Ronald Sobecks ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Strategies ◽  
Targeted Agents ◽  
Advisory Committees ◽  
Survival After Relapse ◽  
Grade Ii

Introduction: Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). While transplant-related mortality has decreased substantially over the last few decades, little progress has been made in outcomes and no standard of care exists for patients (pts) with post-alloHCT relapse. In the recent era, several new therapies, including targeted agents, have been approved for ALL, AML, and MDS. We conducted a study to evaluate outcomes of pts with these diseases who relapse after alloHCT in the contemporary period with routine availability of these newer therapeutic agents. Methods: We performed a single-institution retrospective cohort study to review treatment strategies and outcomes of relapse post-alloHCT. We identified 420 adult pts who received their first alloHCT in 2010-2018 using any conditioning regimen or donor source. Overall, 115 (27%) pts experienced relapse (ALL=17/64 [27%], AML=67/242 [28%], MDS=31/114 [27%]) and were included in the analysis. Results: Myeloablative (54%) matched-unrelated donor grafts (50%) were the most common types of HCTs. Peripheral blood stem cell graft (49%) and bone marrow graft (48%) were used the most. Median time from alloHCT to relapse was 5 (range 1-65) months, and 83% of relapses occurred within the first year. Only 24% and 11% of pts experienced grade II-IV acute and any chronic GVHD prior to relapse, respectively. Seven of 17 pts had Philadelphia chromosome positive ALL. Mutation panel was tested in 56% of AML and MDS. Median follow-up period after relapse was 19 (range 6-80) months. The estimated survival after relapse for all diseases was 32% (95% CI 24-41%) at 6 months, 21% (14-28%) at 12 months, and 14% (8-21%) at 24 months (Fig 1). Excluding pts treated with supportive care only, the majority received a combination of different treatments; pts with ALL received median 3 (range 1-5), pts with AML received median 2 (1-4), and pts with MDS received median 1 (1-3) agent. Targeted therapies used for ALL pts included blinatumomab (n=5) and BCR-ABL targeting tyrosine kinase inhibitors with (n=2) or without (n=4) chemotherapy. Among AML pts, targeted agents were used in 15 pts (sorafenib [n=7], 2 each with enasidenib, gemtuzumab ozagamicin, and ivosidenib, and 1 each with venetoclax and SEL24 [a dual pan-PIM/FLT3 inhibitor]). One pt each was treated with enasidenib, gemtuzumab ozagamicin, and PTC299 (an inhibitor of VEGFA mRNA translation) followed by SEL24 for MDS. Second alloHCTs (n=5) were performed median 5 (range 1-16) months after first HCT and median 1 month (range 0-5 months) after relapse. Two pts received no bridging therapy, while 3 pts received chemotherapy (n=2) or donor lymphocyte infusions (DLI [n=1]) prior to the second transplant. DLI without second transplant was used in 25 pts at a median of 20 (range 3-18) months after ALL relapse, median 2 (range 0-13) months after AML relapse, and median 3 (range 1-5) months after MDS relapse. Following DLI, 53% pts developed GVHD. Targeted therapy was associated with a trend towards better survival compared to other therapies (Fig 2, HR 0.65, 95% CI 0.41-1.03, p=0.06). Based on multivariable analysis, matched unrelated (vs. matched sibling, HR 1.70, p=0.027) or haploidentical donor grafts (HR 2.69, p=0.003), presence of grade II-IV acute GVHD before relapse (HR 2.46, p<0.001), and less than 12 months from HCT to relapse (<6 vs. >12 months, HR 6.34, p<0.001; 6-12 vs. >12 months, HR 3.16, p=0.005) were adverse prognostic features with survival after relapse post-alloHCT (Table 1). Conclusion: Outcomes of pts with ALL, AML, and MDS who relapse following alloHCT remain poor in the contemporary era when several newer therapies, including targeted agents, are available for their treatment. Targeted agents were used only in a minority of post-alloHCT relapses likely due to the combination of pt status, absence of the target mutation, the agents' availability, and other factors. Pts who developed grade II-IV acute GVHD and had shorter "disease-free" duration from unrelated or haploidentical donor grafts had the significantly shorter survival following relapse. More innovative treatment strategies to prevent and treat relapse post-alloHCT are needed. Disclosures Hill: Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celegene: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; Genentech: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding. Anwer:In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Majhail:Atara Bio: Consultancy; Anthem, Inc.: Consultancy; Nkarta: Consultancy; Mallinckrodt: Honoraria; Incyte: Consultancy.

scholarly journals Therapeutic use of glucocorticoids and immunosuppressive agents

2005 ◽  
Vol 133 (Suppl. 1) ◽  
pp. 67-73 ◽  
Author(s):  
Leposava Grbovic ◽  
Miroslav Radenkovic
Keyword(s):  
Organ Transplantation ◽  
Inflammatory Diseases ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Therapeutic Use ◽  
Toxic Effects ◽  
Renal Diseases ◽  
Autoimmune Thyroid ◽  
Beta Adrenoceptor ◽  
Antithyroid Agents

Pharmacotherapy of autoimmune thyroid disease (AITD) is complex. Apart from the replacement hormone therapy, antithyroid agents, beta adrenoceptor blockers and other drugs, in regard to the present symptoms, it also includes the administration of glucocorticoids and immunosuppressive agents. Physiological actions of glucocorticoids are significant in number, well known and described in details. The most prominent pharmacological properties of glucocorticoids, that are important for their clinical use, are antiinflammatory and immunosuppressive actions. In this article, the most notable clinical pharmacology aspects of glucocorticoids have been presented, including the basic principles of their therapeutic use, as well as the most important indications with the examples of dosing regiments (rheumatic disorders, renal diseases, allergic reactions, bronchial asthma, gastrointestinal inflammatory diseases, thrombocytopenia, organ transplantation, and Graves? ophthalmopathy). In addition, adverse and toxic effects of glucocorticoids as well as their interactions with other drugs have been described. Immunosuppressive agents have important role in treatment of immune disorders, including the reduction of immune response in autoimmune diseases and organ transplantation. Apart from glucocorticoids, immunosuppressive agents consist of calcineurin inhibitors (cyclosporine, tacrolimus), antiproliferative and antimetabolic agents (sirolimus, azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide), monoclonal antibodies: anti-CD3 antibody (muromonab-CD3), anti- CD25 antibody (daclizumab), anti-TNF-alpha antibody (infliximab). In this part, the most updated facts about mechanism of action, rational therapeutic use, as well as adverse and toxic effects of immunosuppressive agents have been reviewed.

scholarly journals Itch in Atopic Dermatitis – What Is New?

2021 ◽  
Vol 8 ◽  
Author(s):  
Franz J. Legat
Keyword(s):  
Atopic Dermatitis ◽  
Intracellular Signaling ◽  
Sleep Disturbances ◽  
Skin Diseases ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Inflammatory Skin Diseases ◽  
New Era ◽  
Short And Long Term ◽  
Chronic Pruritus

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

Long Term Neuropsychological Outcomes of Survivors of Young Childhood Brain Tumors Treated on the Head Start II Protocol

2021 ◽  
Author(s):  
Cara F Levitch ◽  
Benjamin Malkin ◽  
Lauren Latella ◽  
Whitney Guerry ◽  
Sharon L Gardner ◽  
...  
Keyword(s):  
Head Start ◽  
Brain Tumors ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Strategies ◽  
Receptive Language ◽  
Age At Diagnosis ◽  
High Dose ◽  
Treatment Protocols ◽  
Significant Change

Abstract Background The Head Start treatment protocols have focused on curing young children with brain tumors while avoiding or delaying radiotherapy through using a combination of high-dose, marrow-ablative chemotherapy and autologous hematopoietic cell transplantation (AuHCT). Late effects data from treatment on the Head Start II (HS II) protocol have previously been published for short-term follow-up (STF) at a mean of 39.7 months post-diagnosis. The current study examines longer-term follow up (LTF) outcomes from the same cohort. Methods Eighteen HS II patients diagnosed with malignant brain tumors &lt;10 years of age at diagnosis completed a neurocognitive battery and parents completed psychological questionnaires at a mean of 104.7 months post-diagnosis. Results There was no significant change in Full Scale IQ at LTF compared to baseline or STF. Similarly, most domains had no significant change from STF, including verbal IQ, performance IQ, academics, receptive language, learning/memory, visual-motor integration, and externalizing behaviors. Internalizing behaviors increased slightly at LTF. Clinically, most domains were within the average range, except for low average mathematics and receptive language. Additionally, performance did not significantly differ by age at diagnosis or time since diagnosis. Of note, children treated with high-dose methotrexate for disseminated disease or atypical teratoid/rhabdoid tumor displayed worse neurocognitive outcomes. Conclusions These results extend prior findings of relative stability in intellectual functioning for a LTF period. Ultimately, this study supports that treatment strategies for avoiding or delaying radiotherapy using high-dose, marrow-ablative chemotherapy and AuHCT may decrease the risk of neurocognitive and social-emotional declines in young pediatric brain tumor survivors.

scholarly journals Allogeneic hematopoietic cell transplantation for XIAP deficiency: an international survey reveals poor outcomes

Blood ◽  
2013 ◽  
Vol 121 (6) ◽  
pp. 877-883 ◽  
Author(s):  
Rebecca A. Marsh ◽  
Kanchan Rao ◽  
Prakash Satwani ◽  
Kai Lehmberg ◽  
Ingo Müller ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
High Mortality ◽  
Hematopoietic Cell Transplantation ◽  
Mortality Rates ◽  
Hematopoietic Cell ◽  
International Survey ◽  
Myeloablative Conditioning ◽  
Key Points ◽  
Conditioning Regimens ◽  
Poor Outcomes

Key Points High mortality rates are observed in patients with XIAP deficiency treated with myeloablative conditioning regimens for hematopoietic cell transplantation.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Hypophysitis: diagnosis and treatment

2018 ◽  
Vol 179 (3) ◽  
pp. R151-R163 ◽  
Author(s):  
Mamta N Joshi ◽  
Benjamin C Whitelaw ◽  
Paul V Carroll
Keyword(s):  
Imaging Techniques ◽  
Immunosuppressive Agents ◽  
Treatment Strategies ◽  
Rare Condition ◽  
Diagnostic Value ◽  
Serum Markers ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Pituitary Mass ◽  
Pituitary Antibodies

Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or as secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies). Hypophysitis can be classified using anatomical, histopathological and aetiological criteria. Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity. Newer serum markers such as anti-rabphilin 3A are yet to show consistent diagnostic value and are not yet commercially available. Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis. Modern imaging techniques, histological classification and immune profiling are improving the accuracy of the diagnosis of the patient with hypophysitis. The objective of this review is to bring readers up-to-date with current understanding of conditions presenting as hypophysitis, focussing on recent advances and areas for future development. We describe the presenting features, investigation and diagnostic approach of the patient with likely hypophysitis, including existing conventional techniques and those in the research/development arena. Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement. Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy. Glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice.

scholarly journals The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence

2014 ◽  
Vol 2014 ◽  
pp. 1-45 ◽  
Author(s):  
Goran B. Klintmalm ◽  
Björn Nashan
Keyword(s):  
Metabolic Syndrome ◽  
Liver Transplantation ◽  
Renal Function ◽  
De Novo ◽  
Immunosuppressive Agents ◽  
Mammalian Target Of Rapamycin ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors

Despite the success of liver transplantation, long-term complications remain, includingde novomalignancies, metabolic syndrome, and the recurrence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). The current mainstay of treatment, calcineurin inhibitors (CNIs), can also worsen posttransplant renal dysfunction, neurotoxicity, and diabetes. Clearly there is a need for better immunosuppressive agents that maintain similar rates of efficacy and renal function whilst minimizing adverse effects. The mammalian target of rapamycin (mTOR) inhibitors with a mechanism of action that is different from other immunosuppressive agents has the potential to address some of these issues. In this review we surveyed the literature for reports of the use of mTOR inhibitors in adult liver transplantation with respect to renal function, efficacy, safety, neurological symptoms,de novotumors, and the recurrence of HCC and HCV. The results of our review indicate that mTOR inhibitors are associated with efficacy comparable to CNIs while having benefits on renal function in liver transplantation. We also consider newer dosing schedules that may limit side effects. Finally, we discuss evidence that mTOR inhibitors may have benefits in the oncology setting and in relation to HCV-related allograft fibrosis, metabolic syndrome, and neurotoxicity.

Diabetes, Hypertension and Cardiovascular Events in Survivors of Hematopoietic Cell Transplantation (HCT): A Report from the Bone Marrow Transplant Survivor Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 699-699 ◽  
Author(s):  
K. Scott Baker ◽  
Kirsten Ness ◽  
Julia Steinberger ◽  
Andrea Carter ◽  
Liton Francisco ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Calcineurin Inhibitors ◽  
Arterial Disease ◽  
Marrow Transplant ◽  
Adjusted Risk ◽  
Allogeneic Hct ◽  
Increased Risk ◽  
Common Diagnosis

Abstract Early evidence indicates that survivors after HCT may be at increased risk for metabolic syndrome (MS), characterized by obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension (HTN). Individuals with MS are at a higher risk for development of cardiovascular disease. The purpose of this analysis was to ascertain the prevalence of self-reported medical late effects including diabetes, HTN, myocardial infarction (MI), stroke, and obesity (body mass index [BMI] of 30 kg/m2 or greater) in a cohort of patients treated with HCT; to compare these outcomes in HCT survivors to a sibling comparison group, and to identify risk factors for these conditions after HCT. Methods: Participants had undergone HCT at either City of Hope or the University of Minnesota for cancer or hematologic disorders between 1974 and 1998 and survived two or more years after HCT. A random sample of siblings of study participants was recruited for comparison. Participants (n=1276 cases, n=383 siblings) completed a 238-item health survey assessing medical conditions and medication use. Results: Median age at HCT was 32.9 yrs (0.2–68.5) and median length of follow-up was 7.1 yrs (2–27) since HCT. The median age at completion of survey was 42.1 yrs (4.1–72.9) for HCT survivors and 41.4 yrs (1.6–78.7) for siblings. HCT survivors were more likely to be male (55.0% vs. 38.9%, p &lt; 0.001) than were siblings. Leukemia was the most common diagnosis (32.6%), 58.8% of survivors received an allogeneic HCT, and 75.9% received total body irradiation (TBI) as part of their conditioning regimen. CGVHD had been diagnosed in 48.5% of allogeneic HCT survivors, and those still receiving calcineurin inhibitors or steroids were excluded from the analysis. Survivors were more likely than siblings to report diabetes (8.0% vs. 3.1%) and HTN (22.8% vs. 15.7%). The prevalence of obesity was 19.8% among siblings and 15.9% among HCT survivors. The proportion of participants reporting arterial disease, a history of MI or stroke was less than 2% in each group. Adjusting for age at survey, age at HCT and sex, HCT survivors were 3.0 times (95% CI: 1.6–5.6) more likely to report diabetes and 1.6 times (95% CI: 1.1–2.1) more likely to report HTN than siblings. HCT survivors who received allo-HCT were 4.1 times (95% CI 2.1–7.9) more likely to report diabetes, 2.3 times (95% CI: 1.6–3.2) more likely to report HTN, and 7.9 times (95% CI 1.1–56.5) more likely to report stroke than siblings, whereas auto-HCT survivors were not more likely than siblings to report any of the conditions in this analysis. HCT survivors who received TBI were only more likely to report diabetes (OR=3.1, 95% CI: 1.5–6.3) than those not exposed to TBI. Allogeneic HCT increased the risk of diabetes (OR=2.1, 95% CI: 1.2–3.3) and HTN (OR= 2.4, 95% CI: 1.7–3.4) compared to autologous HCT. HCT survivors were 30% (95% CI: 10–40%) less likely than siblings to be obese. Conclusions: HCT survivors, particularly those receiving allo-HCT and TBI, have a higher age-adjusted risk of diabetes and HTN that is independent of obesity, and that may predispose them to early cardiovascular events. Appropriate monitoring for the components of MS and interventions to decrease cardiovascular risk should be undertaken in this population.

Prospective Randomized Comparison of Cyclophosphamide Versus Cyclophosphamide Plus Fludarabine In Addition to Anti-Thymocyte Globulin for the Conditioning Therapy In Allogeneic Hematopoietic Cell Transplantation for Bone Marrow Failure Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 34-34
Author(s):  
Hawk Kim ◽  
Jae-Hoo Park ◽  
Je-Hwan Lee ◽  
Young Don Joo ◽  
Won-Sik Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Transplantation ◽  
Failure Rate ◽  
Graft Failure ◽  
Hematopoietic Cell Transplantation ◽  
Bone Marrow Failure ◽  
Pulmonary Complications ◽  
Phase Iii ◽  
Bone Marrow Failure Syndrome ◽  
Conditioning Regimens

Abstract Abstract 34 We performed randomized phase III study to compare the regimen related toxicities (RRT) of two different conditioning regimens, cyclophosphamide (CyATG) vs. cyclophosphamide plus fludarabine (CyFluATG) given in addition to anti-thymocyte globulin (ATG) for allogeneic hematopoietic cell transplantation (alloHSCT) for bone marrow failure syndrome including severe aplastic anemia (AA) and hypoplastic myelodysplastic syndrome (MDS). CyATG consisted of Cyclophosphamide (Cy) 50 mg/kg (D –5 to –2). CyFluATG arm received fludarabine (Flu) 30 mg/m2 (D –6 to –2) and Cy 50 mg/kg (D –3 to –2). Thymoglobuline 3 mg/kg, lymphoglobulin 15 mg/kg on days -4 to -2 or alemtuzumab 20mg on day -4 were infused in both arms. Patients were stratified by stem cell donor (related vs. unrelated). Total 83 patients (40 patients to Cy-ATG and 43 patients to Cy-Flu-ATG) were enrolled from February 2003. All patients except for one patient, who had assigned to Cy-Flu-ATG arm and died during conditioning, received full planed regimen and all planned patients were included in this analysis. Median age was 34 (15-60) years and male patients were 42/83 (50.6%). AA patients were 79 and MDS were 4. Matched sibling donors were 53 (63.9%). ATG was used in form of thymoglobulin (n=75, 90.4%), and some patients had received ALG (n=5, 6.0%) or alemtuzumab (n=3, 3.6%). Median duration from diagnosis to transplantation was 4.7 (0.2-177.7) months. Age, gender, donor type were not different in both arms (Table 1). Various TRT were similar between Cy-ATG and Cy-Flu-ATG (Table 2); granulocyte graft failure rate (p=0.959), platelet graft failure rate (p=0.625), acute GvHD (p=0.388), chronic GvHD (p=0.991), CMV antigenemia (p=0.550), hematuria (p=0.480). However, pulmonary complications (p=0.005) was significantly lower in CyFluATG arm. Infection rate (p=0.130) and sinusoidal obstruction syndrome (SOS, p=0.101) seemed lower in CyFluATG arm but were not statistically significant. Any RRTs were significantly higher in CyATG arm (80.0% vs. 39.5%; p<0.001) but any treatment-related toxicities were similar in both arms (85% vs. 79.1%; p=0.483). Figure 1 shows that 4-year survival rates (77.7% vs. 87.6%) were higher in CyFluATG arm without any statistical significance (p=0.265) and this trend was similar in MRD (81.9 vs. 92.1%; p=0.354) and AD (69.3 vs. 80.2%; p=0.442). In conclusion, overall treatment-related complications and survival were similar between CyATG CyFluATG, however, CyFluATG seemed superior over CyATG in terms of pulmonary complications and RRT.Table 1.Characteristics of patients between Cy-ATG and Cy-Flu-ATGCharacteristicsCy-ATGCy-Flu-ATGp-valueGender, n (%)0.586Male19 (47.5)23 (53.5)Female21 (52.5)20 (46.5)Age, median (range)34.5 (15±59)34.0 (18±60)0.365Months from diagnosis to SCT, median (range)4.8 (0.2–147.2)4.6 (0.9–177.7)0.982Diagnosis, n (%)0.617AA39 (97.5)40 (93.0)MDS1 (1.9)3 (7.0)Infused CD34+ cell dose (?106/kg), mean±SD5.76±4.895.25±5.300.449ATG, n (%)0.360Thymoglobulin38 (95.0)37 (86.0)ALG1 (2.5)4 (9.3)Alemtuzumab1 (2.5)2 (4.7)HLA-A, B, C and DR molecular matching, n (%)0.699Full matched30 (75.0)30 (69.8)1 locus mismatched3 (7.5)3 (7.0)2 loci mismatched3 (7.5)2 (4.7)Not determined4 (10.0)8 (18.6)Donor, n (%)0.834MSD26 (65.0)27 (62.8)AD14 (35.0)16 (37.2)Table 2.The comparison of treatment-related toxicities between Cy-ATG and Cy-Flu-ATGFactorsCy-ATGCy-Flu-ATGp-valueGraft failure, n (%)5 (12.5)7 (16.3)0.625Granulocyte1 (2.5)1 (2.3)0.959Platelet5 (12.6)7 (16.3)0.625Acute GvHD, n (%)Any grades6 (15.0)10 (23.3)0.388Grade 3/42 (5.0)1 (2.3)0.514Chronic GvHD, n (%)Any5 (12.5)5 (11.6)0.991Extensive4 (10.0)3 (7.0)0.369CMV antigenemia, n (%)24 (60.0)23 (53.5)0.550Infection, n (%)32 (80.0)28 (65.1)0.130Interstitial pneumonitis, n (%)0 (0.0)0 (0.0)–Pulmonary complications, n (%)14 (35.0)4 (9.3)0.005SOS, n (%)5 (12.5)1 (2.3)0.101Hematuria, n (%)10 (8.7)8 (29.6)0.480Any regimen-related toxicities, n (%)32 (80.0)17 (39.5)<0.001Any treatment-related toxicities, n (%)34 (85.0)34 (79.1)0.483Figure 1.Overall survivalFigure 1. Overall survival Disclosures: Off Label Use: Cyclophosphamide, Fludarabine and thymoglobulin were used in conditioning regimens of this phase III clinical trial.

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