Long-Term Survival In Patients With Acute Steroid Refractory Graft-Versus-Host-Disease (SR-GVHD) Treated With Infliximab Combined With Daclizumab

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4624-4624
Author(s):  
Sanaz Nicky Soltani ◽  
Ramaprasad Srinivasan ◽  
Theresa Jerussi ◽  
A. John Barrett ◽  
Thomas E Hughes ◽  
...  
Keyword(s):  
High Probability ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival ◽  
Post Transplant

Acute SR-GVHD occurs in approximately 15% of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), and is associated with a 70-90% long-term mortality rate. We previously reported that concomitant blockade of TNF-α and IL-2 pathways with infliximab combined with daclizumab have a synergistic therapeutic effect, with a high probability of complete resolution of SR-GVHD. Although various treatment modalities are effective in the treatment of SR-GVHD, minimal long-term follow up data exists for complete responders to second line treatments. Here we report long-term outcomes in a cohort of 23 subjects developing SR-GVHD treated with infliximab/daclizumab. A consecutive series of 141 patients with a variety of hematological and non-hematological malignancies as well as nonmalignant hematological disorders including severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria and pure red cells aplasia, underwent a reduced intensity allogeneic HSCT from an HLA identical or single antigen mismatched relative at a single institution between 2/2001 and 12/2008. Transplant conditioning consisted of cyclophosphamide (60 mg/kg days -7, -6) and fludarabine (25 mg/m2days -5 to -1) with or without equine ATG or 6-12 Gy of total body irradiation. GVHD prophylaxis was with cyclosporine with or without additional MMF or MTX. Twenty three patients (median age 35 years, range 13-65 years) developed SR-GVHD at a median of 28 days post transplant. SR-GVHD was defined as absence of response to at least 6 days of high dose methylprednisolone therapy. Following a diagnosis of SR-GVHD, patients received a combination of daclizumab (1mg/kg given on days 1, 4, 8, 15, 22), infliximab (10mg/kg given on days 1, 8, 15, 22), broad spectrum bacterial and anti-fungal prophylaxis, and had their methylprednisolone tapered to 1mg/kg/day. Combined cytokine blockade was highly active against SR-GVHD, with 21/23 (87.5%) patients achieving a complete response (CR), defined as total resolution of GVHD in all involved organ systems. All complete responders survived to hospital discharge. With a median follow-up of 9 years (range 5-10 years), 9/23 (39%) survive, including 6 patients without chronic GVHD whose immunosuppressive therapy (IST) has been discontinued and 3 patients with chronic GVHD (2 limited and 1 extensive) who continue to be tapered off IST. Fourteen of 21 patients with resolution of SR-GVHD died a median 173 days post transplant (range 67-1039 days), including 1 from complications related to recurrent SR-GVHD, 6 from progression of malignancy (all solid tumors), 2 from bleeding related to peptic ulcer disease and 5 from infectious complications including invasive fungal infection and CMV disease. A subgroup analysis showed 5/6 patients with SAA developing SR-GVHD had a complete response to combined infliximab/daclizimab. Remarkably, at a median 6 years follow up, 67% (4/6) of these SAA patients were long-term survivors. All these survivors have maintained normal blood counts and remained transfusion independent with 100% donor chimerism in myeloid and T-cell lineages. Conclusion Patients with SR-GVHD treated with infliximab combined with daclizumab had a high probability of achieving a complete response with nearly 40% of patients having long-term survival. This is the first report to show that long-term survival can be achieved in a substantial proportion of patients receiving combined IL-2 and TNF blockade for SR-GVHD. Disclosures: Off Label Use: Infliximab is FDA approved for the treatment of psoriasis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis. Daclizumab gained FDA approval for use in transplant rejection.

Daclizumab Therapy Improves Outcome in Steroid Refractory Acute Graft Versus Host Disease (aGVHD).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5092-5092
Author(s):  
Richard T. Doocey ◽  
Matthew J. Greenwood ◽  
Dawn Warkentin ◽  
Kevin W. Song ◽  
Alan Le ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Gvhd ◽  
Interleukin 2 ◽  
Complete Response ◽  
Cell Transplant ◽  
Phase Ii Trials ◽  
Term Survival ◽  
Post Transplant ◽  
Steroid Refractory

Abstract Steroid refractory aGVHD following allogeneic stem cell transplant (SCT) is associated with a long-term event-free survival (EFS) of less than 20%. Daclizumab is a humanised monoclonal antibody specific for the Tac subunit of the Interleukin-2 (IL-2) receptor. It inhibits IL-2 binding and is thought to be more specific for alloreactive lymphocytes than pan-T cell antibodies. Limited phase II trials using daclizumab for steroid refractory aGVHD have demonstrated 50–60% complete response (CR) rates, though its safety and efficacy as primary aGVHD treatment has recently been questioned. We examined the Vancouver experience with daclizumab in the management of steroid refractory aGVHD. Between 8/00 and 2/04, 35 patients with steroid refractory aGVHD were treated with daclizumab. Male:female ratio was 1.7:1. Median age was 42 years (17–53). Pretransplant diagnoses were AML (n=7), ALL (n=6), CML (n=6), MDS (n=5), NHL (n=6), MM (n=4) and Myelofibrosis (n=1). One patient with relapsed AML post-SCT developed aGVHD following DLI. Stem cell source was matched unrelated bone marrow (BM) (n=11) or peripheral blood (PB) (n=8), mismatched unrelated BM (n=6) or PB (n=3), matched related BM (n=2) or PB (n=4), and mismatched related BM (n=1). Twenty eight pts were conditioned with Cyclophosphamide/TBI. CSP/MTX aGVHD prophylaxis was used in all pts and initial aGVHD therapy consisted of Methylprednisolone 2 mg/kg IV. Grade I-II aGVHD developed in 18/35 (51%) pts and grade III-IV in 17/35 (49%) pts. Median onset of aGVHD was 18 (6–49) days post transplant. Steroid refractory pts received daclizumab 1 mg/kg IV (maximum dose 100mg) on days 1, 4, 8, 15 and 22 at a median of 40 (18–94) days post transplant. Daclizumab response was assessed at day 42 following its initiation. A CR was defined as a return to stage/grade 0 aGVHD and a PR as a reduction of ≥ 1 aGVHD stage/grade without need for additional therapy. There were no significant infusional complications. One patient died during the response assessment period (regimen related pulmonary toxicity). Overall response rate (ORR) was 25/35 (73%), with 15/25 (44%) achieving a CR and 10/25 (29%) a PR. Response was most likely in pts with skin involvement. ORGAN ORR CR PR NR SKIN 25/33 (76%) 18/33 (55%) 7/33 (21%) 8/33 (24%) GUT 15/23 (65%) 7/23 (30%) 8/23 (35%) 8/23 (35%) LIVER 8/14 (57%) 3/14 (21%) 5/14 (36%) 6/14 (23%) SKIN ALONE 9/11 (82%) 8/11 (73%) 1/11 (9%) 2/11 (18%) Twenty four (68%) pts developed limited (n=8) or extensive (n=15) chronic GVHD. The 3-year OS and EFS rates were 35% (95% CI 17–53%) and 28% (95% CI 12–47%), respectively. Female patients had a significantly poorer OS (p=0.0064) and EFS (p=0.0112) as did those pts receiving SCT from female donors (p=.0333 / 0.0456). Eleven patients (31%) received antithymocyte globulin (ATG) in addition to daclizumab. In this subgroup, aGVHD response was more likely but ATG treated patients had increased CMV antigenemia rates during the treatment response period (p=0.01), and a significantly lower EFS (p=0.0064) and OS (p=0.0123). Daclizumab is an effective agent for steroid refractory aGVHD especially if limted to the skin. Long-term survival appears to be superior in pts treated with this agent although its use along with ATG may compromise pt outcome.

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.

scholarly journals Long-term survival in patients with peripheral T-cell non-Hodgkin lymphomas after allogeneic hematopoietic stem cell transplant

2012 ◽  
Vol 53 (6) ◽  
pp. 1124-1129 ◽  
Author(s):  
Jenna D. Goldberg ◽  
Joanne F. Chou ◽  
Steven Horwitz ◽  
Julie Teruya-Feldstein ◽  
Juliet N Barker ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival

Durable Engraftment and Long-Term Survival Following Fludarabine-Based Nonmyeloablative Hematopoietic Cell Transplantation (HCT) in Patients with ATG-Refractory Severe Aplastic Anemia (SAA) and Other Nonmalignant Hematological Disorders.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 252-252 ◽  
Author(s):  
Sakti Chakrabarti ◽  
Y. Takahashi ◽  
R. Srinivasan ◽  
I. Espinoza ◽  
T. Igarashi ◽  
...  
Keyword(s):  
T Cell ◽  
Hematopoietic Cell Transplantation ◽  
Bone Marrow Failure ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Term Survival ◽  
Long Term Survival ◽  
Hematological Disorders ◽  
Post Transplant

Abstract We evaluated the toxicity-profile, engraftment potential, and efficacy of fludarabine-based nonmyeloablative allogeneic HCT in patients with a variety of nonmalignant hematological disorders. Twenty three patients (median age 29 years; range 11–52) with nonmalignant hematological disorders including ATG refractory SAA (n=13), severe paroxysmal nocturnal hemoglobinuria (PNH: n=9), and pure red cell aplasia (PRCA; n=1) were transplanted from 5/99 – 8/2004 at the NHLBI. The majority of patients had an extensive transfusion history including 11/23 who had HLA allo-antibodies and 4/23 with allo-antibodies to RBCs. Conditioning with fludarabine (25 mg/m2 x 5 days), ATG (40mg/kg x 4 days) and cyclophosphamide (60mg/kg x 2 days) was followed by infusion of an un-manipulated G-CSF mobilized allograft from an HLA matched sibling (n=18), parent (n=2), or single antigen mismatched sibling (n=3). GVHD prophylaxis consisted of cyclosporine (CSA) either alone (n=2) or combined with mycophenolate mofetil (n=10) or mini-dose methotrexate (n=11). Despite a high prevalence of pre-transplant allo-immunization, all patients achieved sustained donor engraftment in both myeloid and T-cell lineages. Myeloid recovery (neutrophils >500cells/uL) occurred at a median 14 days post transplant (range 8–18 days). Conversion from mixed to full donor myeloid and T-cell chimerism occurred in all patients by 110 days post-transplant. CMV reactivation occurred in 11/21 patients at risk (KM probability 52%) without any cases of CMV disease. Grade II–IV and III–IV acute GVHD was the major transplant complication occurring in 13/23 (KM probability 60%) and 8/23 (KM probability 38%) patients respectively. Fourteen of 21 evaluable patients developed chronic GVHD (limited in 11 cases), which resolved completely with low-dose alternate day steroids and/or CSA in all but 1 case. One patient who received an allograft from his HLA matched father died 16 months post-transplant from complications related to chronic GVHD. With a median follow up of 25 months (range 1–64 months), 20/21 patients evaluable more than 100 days post-transplant survive in complete remission with full donor chimerism in all lymphohematopoietic lineages (KM probability of long-term survival 92.8 %-see figure ). Conclusion: Fludarabine-based nonmyeloablative transplantation achieves excellent donor engraftment and long-term disease free survival in heavily transfused and allo-immunized patients with ATG refractory SAA and other nonmalignant hematological disorders associated with bone marrow failure.

scholarly journals Biomodulatory Treatment Regimen, MEPED, Rescues Relapsed and Refractory Classic Hodgkin’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Florian Lüke ◽  
Dennis C. Harrer ◽  
Karin Menhart ◽  
Daniel Wolff ◽  
Ernst Holler ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Survival Rates ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Deauville Score ◽  
Institutional Review ◽  
Positron Emission

Introduction: Current combined intensive chemotherapy and radiation regimens yield excellent survival rates in advanced classic Hodgkin’s lymphoma (cHL). However, acute toxicity in elderly, comorbid patients can be challenging and long-term survival in refractory patients remains poor.Patients and Methods: We report on six patients with r/r HL, three patients with long-term follow-up, three newly treated, after biomodulatory therapy. All patients received MEPED (treosulfan 250 mg p.o. daily, everolimus 15 mg p.o. daily to achieve serum trough levels of 15 ng/ml, pioglitazone 45 mg p.o. daily, etoricoxib 60 mg p.o. daily and dexamethasone 0.5 mg p.o. daily). Patients had either received every at that time approved systemic treatment or were ineligible for standard treatment, including immune checkpoint inhibition (ICPi) due to prior demyelinating autoimmune polyneuropathy, myasthenia gravis and previous allogeneic hematopoietic-stem-cell transplant (alloHSCT). Medication was administered continuously from day 1. One patient with relapse after alloHSCT received trofosfamide 50 mg daily instead of treosulfan to avoid risk of increased myelotoxicity. The patients were treated in individual healing attempts outside a clinical trial after institutional review board approval. 18F-fluoro-2-deoxy-d-glucose positron emission tomography combined with computed tomography scan (FDG-PET/CT) was performed to monitor treatment and follow-up.Results: In the three newly treated patients, CT scans showed partial remissions after 2–5 months on MEPED treatment. Two patients had achieved PET Deauville score 2 and 3, while the third remained positive at Deauville score 5. One patient achieving PR became eligible for alloHSCT, while the other two patients continued treatment with MEPED. All patients eventually achieved continuous complete remission (cCR), one after consecutive alloHSCT, one after discontinuing MEPED consolidation for &gt;1 year and one on on-going MEPED consolidation, respectively. Only one patient experienced Grade 3 toxicity (bacterial pneumonia) requiring temporary discontinuation of MEPED for 10 days. All three previously published patients received allo HSCT for consolidation and have achieved cCR.Conclusions: MEPED is well tolerated with low toxicity and highly efficacious in relapsed/refractory cHL, including severely comorbid patients. Due to its immunomodulatory components, MEPED might also have a synergistic potential when combined with ICPi but requires further evaluation within a clinical trial.

Long-Term Survival and Late Deaths After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency Diseases and Inborn Errors of Metabolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3320-3320
Author(s):  
Mary Eapen ◽  
Kwang Woo Ahn ◽  
Paul Orchard ◽  
Morton Jerome Cowan ◽  
Stella M. Davies ◽  
...  
Keyword(s):  
General Population ◽  
Causes Of Death ◽  
Transplant Recipients ◽  
Inborn Errors ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival ◽  
Matched Sibling

Abstract Abstract 3320 Poster Board III-208 Late mortality in children who have undergone hematopoietic stem cell transplantation (HCT) for severe combine immunodeficiency (SCID), non-SCID immune diseases and inborn errors of metabolism (IEM) has not been studied. The goals of the current analyses were to: 1) determine the probability of long-term survival after HCT in patients who survive the first 2 years after HCT; 2) identify risk factors for late deaths; and 3) determine excess mortality relative to rates in an age and sex-matched general population. Nine hundred and sixty patients with >95% donor chimerism or recovery of T-cell function who survived at least 2 years after their transplantation were included in the study. Two hundred and one patients had SCID, 407, non-SCID immune diseases and 352, IEM. Seventy percent of SCID transplant recipients received grafts from an HLA-matched sibling or mismatched relative. Fifty six percent of non-SCID and IEM transplant recipients received grafts from unrelated donors, 32% from a matched sibling and 12% from a mismatched relative. All transplantations occurred in 1980 – 2003; the median follow-up of surviving patients was 7 years. Median ages of long-term survivors were 7, 9 and 10 years for SCID, non-SCID immune diseases and IEM, respectively. Because of differences in biologic features and transplant strategies for SCID, non-SCID immune diseases and IEM, the disease groups were analyzed separately. The 7-year probabilities of overall survival were 93%, 96% and 90% for SCID, non-SCID immune diseases and IEM, respectively. No patient, disease or transplant characteristic was associated with late deaths in patients with SCID. For non-SCID immune diseases, late deaths were higher in recipients of T-cell depleted grafts (RR 4.63, p=0.003). For IEM, late deaths were higher after unrelated donor (RR 2.75, p=0.018) and mismatched related donor (RR 2.77, p=0.042) transplants compared to matched sibling donor transplant. There were 69 late deaths with 52 occurring 2 – 6 years after transplantation and 17 after 6 years. Causes of death in patients who died between 2 – 6 years included: chronic graft-versus-host disease [CGVHD] (n=12), infection including encephalitis (n=11), organ failure (n=12), post-transplant lymphoproliferative disease (n=4), primary disease (n=5), acute abdomen (n=1), status epilepticus (n=1), acute myeloid leukemia (n=1), accidental death (n=1) and not reported (n=3). Causes of death beyond 6 years included CGVHD (n=1), infection including encephalitis (n=3), organ failure (n=4), primary disease (n=2), acute abdomen (n=1), brain stem glioma (n=1) and not reported (n=5). The table below shows the estimated excess deaths per 1000 compared to an age- and sex-matched general population at 2 – 6 years and beyond 6 – 10 years after HCT. Though the risk of late deaths in this population is in excess of that for the general population for several years after transplantation, with extended follow up, the risk appears to decrease towards normal rates. Beyond 6 years after HCT, among patients transplanted for SCID and non-SCID immune diseases, the risk of mortality does not differ significantly from the general population whereas for patients with IEM, mortality rates continue to be higher than that in the general population. Screening programs aimed at identifying late complications together with planned intervention may improve long-term survival in these patients. Excess deaths per 1000 (95% confidence interval) SCID Non-SCID IEM 2 – 6 years after HSCT 54 (28, 79)* 41 (28, 53)* 95 (82, 109)* 6 – 10 years after HSCT 25 (0, 51) 16 (0, 39) 45 (27, 62)* * Significant differences in mortality risks compared to the general population Disclosures No relevant conflicts of interest to declare.

Locoregional therapies as a bridge to transplant in patients with hepatocellular carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15608-e15608
Author(s):  
S. S. Sakaria ◽  
R. Dhanasekaran ◽  
M. Pankonin ◽  
S. Parekh ◽  
J. S. Kauh ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Survival Rates ◽  
Definitive Treatment ◽  
Transcatheter Therapy ◽  
Term Survival ◽  
Long Term Survival ◽  
Post Transplant ◽  
Locoregional Therapies

e15608 Background: Orthotopic liver transplantation (OLT) has been widely established as the definitive treatment for patients with HCC who fit within the Milan criteria. The limited availability of donor organs results in prolonged waiting periods leading to tumor progression and potential disqualification for OLT. As a result, there has been a rising interest in locoregional therapies that may stall tumor progression until a donor organ is available for transplantation. Methods: We reviewed patients with a diagnosis of HCC on the transplant list between 1998 and 2008. Of these patients, 72 patients received locoregional therapies (LRT). The various LRT consisted of transcatheter therapy alone (29 patients); combination transcatheter therapy and radiofrequency ablation (RFA) (33 patients), and RFA alone (10 patients). Kaplan Meier method with the log rank test and Cox proportional hazards method were used for survival analysis. Results: Of the 72 patients, 71% (51/72) were transplanted and 29% (21/72) dropped out. The reasons for drop-out from the transplant list included tumor progression (4.2%); condition deteriorated (11.1%); death (6.9%); refusal of transplant (2.7%); other causes (4.2%). The long term survival rates in the transplanted patients at 1 yr, 2 yrs and 5 yrs is 90%, 87% and 72%. The long term survival in the non-transplanted patients at 1 yr and 2 yrs is 47% and 33% respectively. Mean duration from the first LRT to OLT was 126 days (SD 208). In patients who dropped out, mean duration from the first LRT to the removal date was 143 days (SD 256). The mean post transplant follow-up period was 758 days (SD 527). No recurrence was found in the post transplant follow- up. Conclusions: Locoregional therapies can be effectively used as a bridging therapy to treat patients with HCC awaiting transplant. The long term recurrence-free survival in patients who received OLT after bridging therapies demonstrated 5-year survival rates of 72% and no recurrence after transplant. No significant financial relationships to disclose.

Clinical Features and Outcome of Thrombotic Microangiopathies: Comparison between Patients with and without Malignancy

2020 ◽  
Author(s):  
Andry Van de Louw ◽  
Austin Cohrs ◽  
Douglas Leslie
Keyword(s):  
Hospital Mortality ◽  
Cancer Patients ◽  
Case Series ◽  
Large Data ◽  
Sensitivity Analyses ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival

AbstractThrombotic microangiopathy (TMA) is an uncommon complication of cancers, related to the malignancy itself, antineoplastic drugs, or hematopoietic stem cell transplant. It was reported mostly as case series but large data are lacking. We used the large U.S. MarketScan database to compare TMA between patients with and without malignancy. Adult patients hospitalized between 2005 and 2014 with a diagnosis of TMA were included; cancer patients were defined by a diagnosis of cancer within 1 year prior to or during the admission with TMA. Associated inpatient diagnoses, procedures, hospital mortality, and long-term survival were collected. We included 3,227 patients; 617 (19.1%) had cancer (age 54 [44–60] years, 58% female), which was a new diagnosis for 23% of patients. Two-thirds of cancer patients had solid tumors (mostly pancreas, lung, breast, colorectal, and hepatobiliary, half of them metastatic) and one-third had hematological malignancies (lymphoma, acute leukemia, and multiple myeloma); TMA patients with cancer were older, more often men, had more noncancer-related comorbidities, and developed more sepsis and coagulopathy than TMA patients without cancer. Hospital mortality was significantly higher in cancer patients (16.6% vs. 6.1%, p < 0.001) and reached 30% in transplant recipients; malignancy was an independent risk factor for hospital mortality in multivariate analysis and sensitivity analyses excluding patients with metastases or patients who did not undergo plasmapheresis led to similar results. Malignancy was also associated with decreased long-term survival.

scholarly journals Preemptive interferon-α treatment could protect against relapse and improve long-term survival of ALL patients after allo-HSCT

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sining Liu ◽  
Xueyi Luo ◽  
Xiaohui Zhang ◽  
Lanping Xu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Multiparameter Flow Cytometry ◽  
Interferon Α ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival

AbstractRelapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Multiparameter flow cytometry and polymerase chain reaction assays were applied for MRD monitoring. Recombinant human IFN-α-2b injections were administered subcutaneously twice weekly in every 4 weeks cycle. Twenty-four (35.3%), 5 (7.4%), 6 (8.8%), and 13 (19.1%) patients achieved MRD negativity at 1, 2, 3, and > 3 months, respectively, after treatment. Seven patients showed grade ≥ 3 toxicities after IFN-α treatment. The 4-year cumulative incidence of total acute graft-versus-host disease (aGVHD), severe aGVHD, total chronic GVHD (cGVHD), and severe cGVHD after treatment was 14.7%, 2.9%, 40.0%, and 7.5%, respectively. The 4-year cumulative incidences of relapse and non-relapse mortality after treatment was 31.9% and 6.0%, respectively. The 4-year probabilities of disease-free survival and overall survival after IFN-α treatment were 62.1% and 71.1%, respectively. Thus, preemptive IFN-α treatment could protect against relapse and improve long-term survival for ALL patients who had MRD after allo-HSCT. The study was registered at https://clinicaltrials.gov as #NCT02185261 (09/07/2014).

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