Hyperlipidemia After Allogeneic Stem Cell Transplantation: Prevalence, Risk Factors and Impact on Prognosis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3458-3458
Author(s):  
Yuki Kagoya ◽  
Sachiko Seo ◽  
Yasuhito Nannya ◽  
Mineo Kurokawa
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Calcineurin Inhibitors

Abstract Abstract 3458 Introduction: Hyperlipidemia is one of the late complications after allogeneic stem cell transplantation (SCT). Although intrahepatic cholestasis caused by chronic graft-versus host disease (GVHD) or calcineurin inhibitors has been considered to be one of the etiologies, its prevalence, risk factors, and the impact on prognosis have not been investigated well. Methods: We performed a retrospective analysis of 194 adult patients who underwent allogeneic SCT between 1995 and 2008 in our institute, and survived more than 100 days after SCT. Hypercholesterolemia or hypertriglyceridemia was defined as more than 240 mg/dl or 200 mg/dl, respectively, at two successive tests at least one week apart after the first 100 days after SCT. Cumulative incidence of hypercholesterolemia or hypertriglyceridemia was analyzed. The time to the development of hypercholesterolemia or hypertriglyceridemia was calculated and the multivariate analysis of pre- and posttransplant variables was performed by a Cox proportional hazards model. Chonic GVHD, chronic liver dysfunction (CLD; defined as more than twice the upper limit of normal for aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase, or total bilirubin >3 mg/dl over 3 months) and administration of calcineurin inhibitors were studied as posttransplant factors, which were assessed as time-dependent variables. To analyze the prognosis of patients who developed persistent hyperlipidemia, the multivariate analysis of overall survival (OS), relapse rate, and non-relapse mortality (NRM) was carried out by a landmark approach. Persistent hyperlipidemia was defined as hypercholesterolemia or hypertriglyceridemia continuing more than 3 months. Results: Overall, 83 (42.8%) and 98 (50.5%) patients developed hypercholesterolemia and hypertriglyceridemia, respectively. The median follow-up period of serum cholesterol and triglyceride values in surviving patients was 44 months. The cumulative incidence of each abnormality at 3 years after SCT was 38.1% (95% confidence interval [CI]: 31.0–45.1%), and 46.0% (95% CI: 38.8–52.9%), respectively. In a multivariate analysis, the development of chronic GVHD was independently associated with both hypercholesterolemia (hazard ratio [HR] 2.05, 95% CI: 1.23–3.43, P<0.01) and hypertriglyceridemia (HR 2.04, 95% CI: 1.30–3.18, P<0.01). Besides, CLD was significantly associated with hypercholesterolemia (HR 2.20, 95% CI: 1.39–2.50, P<0.01). Administration of calcineurin inhibitors was not an independent risk factor for the development of hypercholesterolemia (HR 1.23, 95% CI: 0.73–2.08, P=0.43) or hypertriglyceridemia (HR 1.03, 95% CI: 0.61–1.54, P=0.89). Among pretransplant factors, prior hypercholesterolemia and hypertriglyceridemia were associated with posttransplant hypercholesterolemia (HR 2.76, 95% CI: 1.07–7.17, P=0.04) and hypertriglyceridemia (HR 2.04, 95% CI: 1.27–3.27, P<0.01), respectively. Persistent hyperlipidemia was found in 49 patients (25.3%), of which 35 patients (71.4%) developed hyperlipidemia within one year. The median interval to the occurrence of hyperlipidemia of the patients was 180 days after SCT. In univariate analysis, patients with persistent hyperlipidemia had a tendency of better 3-year OS (77.3% vs 64.7%, P=0.23). Multivariate analysis showed that the development of persistent hyperlipidemia was independently associated with better OS (HR: 0.49, P=0.049). Further, although not statistically significant, patients with persistent hyperlipidemia had a tendency of lower 3-year cumulative relapse rate (15.7% vs 20.3%). There were no significant differences in 3-year NRM between patients with or without hyperlipidemia (12.3% vs 13.9%). Conclusions: Both hypercholesterolemia and hypertriglyceridemia are very common complications after SCT. Patients with persistent hyperlipidemia, however, have significantly better OS. Considering a strong association between the development of hyperlipidemia and chronic GVHD, and a tendency of lower relapse rate in patients with persistent hyperlipidemia, hyperlipidemia is regarded as one of the symptoms accompanied with chronic GVHD. Unless severe, its incidence indicates a better control of the primary disease and an improved prognosis. Disclosures: No relevant conflicts of interest to declare.

Incidence, Risk Factors and Outcomes of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3365-3365
Author(s):  
Chiaki Nakaseko ◽  
Shinnichi Ozawa ◽  
Miki Nishimura ◽  
Miwa Sakai ◽  
Kumi Ohshima ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Respiratory Failure ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Bronchiolitis Obliterans ◽  
Chronic Gvhd ◽  
Time Interval

Abstract Background: Bronchiolitis obliterans (BO) after allogeneic stem cell transplantation (allo-SCT) is a late-onset, life-threatening respiratory complication which significantly reduces patients’ quality of life. Despite different therapeutic protocols, BO mortality remains high and most patients die of respiratory failure or infections. In recent practice, the source of stem cells and the conditioning regimen for allo-SCT have become more varied, but their influence on the incidence of BO is not established. Here, we retrospectively analyzed incidence of and risk factors for BO in allo-SCT protocols. Patients and methods: Between Jan 1994 and June 2005, 2692 patients underwent allo-SCT in 14 facilities of the Kanto Study Group for Cell Therapy (KSGCT) in Japan, and 2154 surviving at least 100 days after transplantation were evaluated in this study. Clinical diagnosis of BO was made by pulmonary function tests (PFT) revealing a forced expiratory volume for 1 second (FEV1) less than 70% and FEV1/forced vital capacity less than 80% of the predicted value, along with typical changes on high-resolution computed tomography. Results: BO developed in 57 patients with a cumulative incidence at 5 years post transplant of 2.6%. The Kaplan Meier estimate of median time interval from transplant to diagnosis of BO was 335 days (83–907). The cumulative incidence of BO at 5 years was 1.62% (12/691) in bone marrow transplants from related donors (R-BMT), 3.83% (16/424) in peripheral blood stem cell transplantation from related donors (R-PBSCT), 2.91% (24/808) in BMT from unrelated donors (UR-BMT), and 2.65% (5/199) in unrelated cord blood transplantation (CBT). The incidence of BO after R-PBSCT was significantly higher than after any other type of allo-SCT (p=0.02). At BO diagnosis, the mean value of FEV1% decreased to 52.1% from 82.2% pre-transplant. 94% of patients had already developed chronic GVHD before the onset of BO. Risk factors for BO by univariate analysis were R-PBSCT (p=0.019) and preceding chronic GVHD (p=0.000). Twenty eight patients died after developing BO, 21 of respiratory failure. Only one patient died of relapse of primary disease. Overall 5 yr-survival of patients with BO from the time of diagnosis was 46.5%, significantly less than for those without (76.2% from day 335, p=0.000) by semi-landmark analysis. Conclusions: The incidence of BO in CBT recipients was higher than R-BMT recipients and not significantly different with UR-BMT recipients. R-PBSCT recipients who have already developed chronic GVHD have a higher risk for developing BO and need extensive care and repeated PFT examinations.

Fatal Infectious Complications Developing Late after Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3239-3239
Author(s):  
Andreas Bjorklund ◽  
Johan Aschan ◽  
Olle Ringden ◽  
Jacek H. Winiarski ◽  
Per T. Ljungman
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Control Group ◽  
Cmv Infection ◽  
Respiratory Dysfunction

Abstract Background and aim: The procedure of allogeneic stem cell transplantation (SCT) has evolved during the past decades. Infectious complications are still a major problem contributing to the transplantation related mortality (TRM). The epidemiology and outcome of early infections after SCT are well described. However, less is known has about late infections after SCT. Thus, the aim of this study was to determine risk factors for fatal infections occurring later than 6 months after allogeneic SCT. Material and methods: Our study is based on 938 consecutive SCT patients transplanted 1976–2003 of whom 688 (73%) had survived for at least 6 months after SCT. A retrospective chart review was performed identifying 44 (6.4%) patients surviving for at least 6 months, having died from infection. Patients who had relapsed in their malignant disease were excluded. A control group of 176 patients (4 per case) was identified using relapse-free survival for at least 6 months and year of SCT as the matching criteria. Five controls were excluded leaving 171 patients in the control population. Risk factors for death from late infections were identified by logistic regression. Results: 29 patients (66%) developed their fatal infection within 18 months and 37 (84%) within 5 years after SCT. 37 patients (84%) had ongoing chronic graft versus host disease (GVHD) and 36/44 (82%) had ongoing immunosupression at the time of death. 57 controls had died after 6 months from SCT; 32 of 57 from relapse. Comparing patients and controls in univariate analyses, the mean age was 30.6 years in the cases and 26.5 years in the controls (p=.13). 22/44 (50%) cases had been transplanted from an unrelated or mismatched donor, compared to 57/171 (33%) controls, p=.053; and 35/44 (80%) cases had received a conditioning regimen including myeloablative dose of TBI compared to 113/171 (66%) in the control group, p&lt;.05). Regarding post-transplant complications 40/44 (91%) cases had experienced cGVHD compared with 101/171 (59%) controls, p&lt;.001. 21/44 (48%) cases had developed obstructive respiratory dysfunction compared with 46/171 (27%) controls, p=.01; and more cases (33/44; 75%) than controls (85/171; 50%;) had experienced CMV infection. In multivariate analysis chronic GVHD (OR 9.2; p&lt;.001), use of a mismatched or unrelated donor (OR 4.8; p&lt;.001), and having had a CMV reactivation (OR 8.3; p=.004) increased the risk. Age, acute GVHD, TBI or obstructive respiratory dysfunction had no significant impact on the risk for late fatal infection. Conclusion: Infections later than 6 months after SCT are important contributors to late TRM. Risk factors for late fatal infections include chronic GVHD, use of alternative donors and CMV infection.

Clostridium Difficile Infections After Allogenic Hematopoietic Stem Cell Transplantation: Comparison of Cord Blood to Other Grafts

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4573-4573
Author(s):  
Kohei Hosokawa ◽  
Masanori Tsuji ◽  
Hideki Araoka ◽  
Kazuya Ishiwata ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Clostridium Difficile ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Hematopoietic Stem

Abstract Abstract 4573 Background: Clostridium difficile, a gram-positive sprore-forming anaerobic bacillus, associated diarrhea (CDAD) is a major cause of nosocomial antibiotic-associated diarrhea. Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of developing CDAD during the early posttransplant period due to prolonged exposure to broad-spectrum antibiotics and immunosuppressive agents. The incidence of CDAD has been increasing up to as high as 20% in allogeneic bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT). Although cord blood transplant (CBT) recipients are subjected to delayed immune constitution and high incidence of infectious complications to be risk factors for CDAD, the frequency of CDAD after CBT is unclear. We therefore retrospectively investigated the incidence and clinical features of CDAD in patients receiving CBT. Objectives/Methods: During the 2-yr retrospective period (2007–2008), 201 allogeneic HSCT were performed at the Department of Hematology of Toranomon Hospital: 135 CBT, 39 BMT and 27 PBSCT. The median age of the patients was 56 yr (range, 19–82 yr). All patients with diarrhea had a minimum of one diarrheal stool sample evaluated for the presence of toxin A. A patient found to have toxigenic Clostridium difficile by ELISA was diagnosed as CDAD. The cumulative incidence of CDAD was calculated using the Gray method considering death without CDAD as a competing risk. Overall survival (OS) was estimated by the Kaplan-Meier method. The time-dependent Fine and Gray proportional hazards model was used for multivariate analysis. Results: CDAD developed within 100 days in 11 out of 135 CBT recipients at a median onset of day 18 (range, 3–56 days). The cumulative incidence of CDAD after CBT was 9% at day 100 (Fig 1), which was similar to that after BMT (6%, P= 0.55) and to that after PBSCT (16%, P=0.27). All 17 patients who developed CDAD were successfully treated with using oral metronidazole or oral vancomysin. Of the 17 patients with CDAD, 7 (41%) died within 100 days after transplant, and the direct cause of death was irrelevant to CDAD in the 7 patients. The 1-yr survival after diagnosis of CDAD was 58%, which was comparable to that in patients without developing CDAD (59%, P=0.98). The univariate analysis failed to identify any significant risk factors for CDAD as well as the multivariate analysis. Conclusions: The current study showed that CDAD developed early after CBT at the incidence similar to BMT or PBSCT, and that prompt treatment for CDAD may work in improving its prognosis. It is therefore essential to recognize CDAD as one of the differential diagnosis of diarrhea because it is treatable complication after HSCT. Disclosures: No relevant conflicts of interest to declare.

The Impact of ATG/Alg in Preconditioning On the Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4185-4185
Author(s):  
Koji Kato ◽  
Yoshiko Atsuta ◽  
Kazuteru Ohashi ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Cell Sources ◽  
The Impact

Abstract Abstract 4185 Background: Since the clinical implication of anti-lymphocyte globulin (ATG/ALG) in allogeneic stem cell transplantation (allo-SCT) is not fully understood, we tried to identify the clinical impact of ATG/ALG in patients with acute leukemia who received allo-SCT in Japan. Patients and Methods: We analyzed patients with ALL (n=5494) and AML (n=8115) who received first allogeneic SCT from 1983 to 2009 with (n=356) or without (n=13253) ATG/ALG. Their stem cell sources were bone marrow (BM, n=9056), peripheral blood (PB, n=1918), and cord blood (CB, n=2575) and they were transplanted at 1st complete remission (CR1, n=5681), 2nd CR (CR2, n=2495), and advanced stages (>CR3, n=5033). Results: Five year overall survival (5y OS) of all patients with or without ATG/ALG was 33.6% vs 44.5%, respectively (P<0.001) and multivariate analysis showed that ATG/ALG significantly reduced acute GVHD (P<0.001, HR=1.980) as well as chronic GVHD (P<0.001, HR=1.894). According to stem cell sources, 5y OS with or without ATG/ALG was 35.8% vs 47.5% (P<0.001) in BM, 34.7% vs 37.6% (P=0.067) in PB and 18.3% vs 39.9% (P<0.001) in CB. By multivariate analysis, ATG/ALG significantly reduced A-GVHD (P=0.005, HR=1.565) but decreased OS (P=0.004, HR=0.729) in BM, it reduced A-GVHD (P<0.001, HR=2.376) and C-GVHD (P<0.001, HR=2.691) but lowered engraftment (P=0.046, HR=0.810) in PB, and it increased TRM (P=0.004, HR=0.437) with decreased OS (P=0.011, HR=0.576) in CB. In Haplo transplantation (SCT from 2 or 3 antigens of HLA mismatched family donor, n=337), multivariate analysis showed that ATG/ALG did not affect the relapse, TRM and OS but, it significantly lowered engraftment (P=0.002, HR=0.602), and reduced A-GVHD (P<0.001, HR=2.622) as well as C-GVHD (P<0.001, HR=3.834). In contrast to these results, ATG/ALG did not affect the relapse rate irrespective of stem cell source or diagnosis. Conclusion: In allogeneic stem cell transplantation for patients with ALL and AML, ATG/ALG contribute in reducing acute and chronic GVHD without affecting relapse rates but it was a risk factor of OS for patients who received BM or CB. Disclosures: No relevant conflicts of interest to declare.

Donor Lymphocyte Infusions and Second Transplantation as Salvage Treatment for Relapsed Myelofibrosis After Reduced-Intensity allografting.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1300-1300
Author(s):  
Nicolaus Kröger ◽  
Evgeny Klyuchnikov ◽  
Daniel Wolff ◽  
Martin Bornhäuser ◽  
Guido Kobbe ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Complete Loss ◽  
Donor Lymphocyte Infusions

Abstract Abstract 1300 Introduction: Around 20–30% patients (pts) with primary myelofibrosis (PMF) experience relapses within 3 years after dose-reduced conditioning followed by allogeneic stem cell transplantation (HSCT). The prognosis for those pts is unclear, and standard treatment recommendations have not yet been proposed. Early withdrawal of post-transplant immunosuppression, use of dose escalating donor lymphocyte infusions (DLIs), and/or 2nd HSCT have been suggested as therapeutic options for pts relapsing after HSCT. Although DLIs were found to be effective in certain disease as salvage approach, the role of 2nd HSCT for non-responding patients remains controversial. Here we report on our multicenter experience on the use of a two-stage salvage strategy including DLIs and a 2nd RIC-HSCT in pts with post-transplant relapse of PMF. It was planned to start salvage therapy with DLI and only non-responding patients as well as patients with transformation to blast crisis and complete loss of donor chimerisms were assigned to receive a second allogeneic stem cell transplantation. Responses were evaluated using the International Working Group consensus criteria for treatment response in myelofibrosis. Additionally, the JAK2V617F mutation level (in 1 case, the MPLW515mut level) and donor chimerism were used to assess the molecular remission status. Patients/Methods: Thirty pts with morphologic (n=24) or molecular (n=6) relapse of PMF after 1st HSCT were proceeded to a salvage strategy, including DLIs and/or 2nd RIC-HSCT. Median time from transplantation to relapse was 9 months (range, 2–62). 26 pts received a median of 3 (range, 1–5) DLIs. The initial median dose was 1.2×106 (range, 0.3×104 – 8×107) consequently being increased up to 4×107 CD3+ cells/kg (range, 1×107 – 1.3×108). As a second stage, 13 non-responding pts as well as those who received no DLIs (transformation to blast phase, n=1; complete loss of donor chimerism, n=3) underwent a 2nd RIC-HSCT. The median interval between 1st and 2nd HSCTs was 17 months (range, 11–77). The majority of the patients received a reduced busulfan/fludarabine conditioning regimen for the 1st HSCT. Conditioning regimen at the 2nd RIC-HSCT for most pts (12/17, 71%) consisted of a combination of treosulfan (30-36 g/m2) with fludarabine (150-180 mg/m2), and anti-thymocyte globuline (Thymoglobulin®, 2.5–8 mg/kg). The majority of pts (15/17, 82%) received 2nd allografts from alternative unrelated (HLA-matched, n=8; mismatched, n=5), related (matched, n=1), and haploidentical donors (n=1). Results: After DLIs, responses were observed in 10/26 pts (39%; complete remission (CR): n=8; CRu (unconfirmed: no bone marrow histology: n=2). All pts maintain the response during a median follow-up of 31 months (range, 13–45). Acute (grade II-IV) and chronic GvHD occurred in 3/26 (12%) and 7/25 (28%) pts, respectively There were no cases of non-relapsed mortality (NRM), while 3/26 pts expired from progression. Seventeen pts received a 2nd RIC-HSCT and engraftment was documented in 16/17 pts (leukocytes: median, d +14; platelets: median, d +18). Responses were observed in 12/15 evaluable pts (80%; CR, n=8; CRu, n=1; partial remission (PR), n=3). Acute (II-IV) and chronic GvHD were observed in 8/17 (47%) and 6/14 pts (43%), respectively. The 1-year cumulative incidence of NRM was 6% (95% CI: 0%-18%). The cumulative incidence of relapse at 1 year was 24% (95% CI: 0%-50%). Overall for whole study population, after a median follow-up of 27 mo (range, 9 – 61), the 2-year probabilities of OS and PFS was 80% (95% CI: 62% - 98%) and 72% (95% CI: 52% - 92%), respectively. Conclusions: DLIs and/or 2nd HSCT are effective and well tolerated salvage approaches, which resulted in the majority of patients in long-term freedom from disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Age on Hospitalization and Readmission on Post Allogeneic Stem Cell Transplantation Outcome, Single Center Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4122-4122
Author(s):  
Eshrak Al-Shaibani ◽  
Shiyi Chen ◽  
Wilson Lam ◽  
Arjun Law ◽  
Ivan Pasic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hospitalization Period

Abstract Background: Recent advances and improvement of supportive care allowed allogeneic stem cell transplantation (HCT) to be offered to selected older patients. However, data regarding outcome and factors affecting the outcomes are limited. Method: We retrospective analyzed the outcome in 332 patients, median age 65 years (60-76), who underwent HLA-matched related (n=85), matched unrelated (n=205) and haploidentical donor (n=42) HCT, between January 2014 to December 2019. Of these 60% were male. Diagnosis was leukemia: 193, MDS: 76, MF: 46 and others: 17. Graft source was PBSC in 98%. Reduce-intensity conditioning regimen was used in 95%, and in vivo T-cell depleted in 89% of patients. We categorized them to 3 age-groups (G): G1 60-65y, (n=175), G2 &gt;65-70y (n=127), and G3 &gt;70y (n=30).Cox models were used to compare the rates of overall survival (OS), non-relapse mortality( NRM), event free-survival (EFS), length of hospitalization for HCT, GVHD and reasons of re-hospitalization during the first year post HCT. Results: The median follow up was 14 months (range: 1-123 months). Median days of hospitalization during HCT period were 30-days (range: 20-132 days), with trend towards significance when stratified by age group (p=0.049). HCT-CI scores were 0-1 (n=143), 2-3 (n=107) and &gt;3 (n=70). The cumulative incidences of grade II-IV acute-GVHD was 38.3% and 16.3% for grades III-IV. Moderate-severe chronic-GVHD was 23.7%. Increasing age was not associated with increases in acute GVHD (p=0.86) or chronic-GVHD (p= 0.6). Overall, 188 (56%) patients were re-hospitalized within the first 6-month of HCT, and 61 (18%) in the second 6-month period. The 2-year OS rate (Fig 1) were 56% in G1, 53% in G2 and 34% in G3 (p=0.05). The 2-year EFS rate (Fig 2) were 54% for G1, 49% for G2, and 31% for G3 (P=0.04). Cumulative incidence of NRM at 2-year (Fig 3) were 25% in G1, 36% in G2 and 52% in G3 (p=0.008). Further results are illustrated in Table 1. Risk factors such as age, KPS, HCT-CI, donor-type, readmission and GVHD were analyzed for their associations with outcomes using univariate analyses, those with significant results entered in multivariate-analysis Table 2. Patients aged 60-≤65 had significantly better EFS (p=0.04) and associated with a border line significant trend for lower NRM (p=0.05) than those aged &gt;70. Re-admission in the first 6-month post HCT had a significant impact on the OS, EFS and NRM. HCT-CI &gt;3 had significant impact on NRM. Conclusion: Age had a significant impact on hospitalization period during HCT. Age &gt;70 had significant impact on EFS and trend toward higher NRM. HCT-CI, acute and chronic-GVHD and readmission in first 6-month post-HCT were significant risk factors. Readmission in the first 6 months correlated with lower OS, EFS and higher NRM. Acute GVHD III-IV or moderate-severe chronic GVHD associated with poor outcomes. Selecting patients based on HCT-CI, and good management of GVHD and post-HCT complication may improve the clinical outcome. Figure 1 Figure 1. Disclosures Law: Novartis: Consultancy; Actinium Pharmaceuticals: Research Funding. Kim: Bristol-Meier Squibb: Research Funding; Pfizer: Honoraria; Paladin: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Lipton: Bristol Myers Squibb, Ariad, Pfizer, Novartis: Consultancy, Research Funding.

Low Dose Alemtuzumab (Campath 1H) Prior to Allogeneic Stem Cell Transplantation Is Associated with Low Incidence of Acute and Chronic GVHD but Protracted Immune Recovery.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5376-5376
Author(s):  
Marcel P. Devetten ◽  
Fausto Loberiza ◽  
Robin Weisenborn ◽  
Pam Bunner ◽  
Jamie Brewer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Low Dose ◽  
Chronic Gvhd ◽  
High Dose ◽  
Low Incidence ◽  
Cmv Reactivation

Abstract Background: The administration of alemtuzumab (Campath 1H) as part of the conditioning regimen prior to allogeneic stem cell transplantation has been associated with a low incidence of acute and chronic GVHD. Initial studies employing doses of 100 mg have reported a high incidence of viral infections. Lower alemtuzumab doses combined with standard GVHD prophylaxis regimens (calcineurin inhibitor + MTX) have also resulted in a low incidence of acute GVHD in patients with CD52-positive malignancies. We investigated the effect of low-dose (40 mg) alemtuzumab on engraftment (VNTR chimerism studies), the incidence of acute and chronic GVHD, CMV reactivation, survival, and immune reconstitution (examined by TREC content at various time points after transplant). Patient and Transplant characteristics: Twenty-seven patients underwent a matched (n=24) or 1-antigen mismatched (n=3) related (n=13) or unrelated (n=14) allogeneic stem cell transplantation for various hematologic malignancies. Median age was 41 years (19–59). Disease stage at transplant was early for 48%, intermediate for 11% and late for 41%. Three patients received bone marrow and 24 received PBSC grafts. Conditioning regimen consisted of TBI 10 Gy with partial lung shielding, Thiotepa 500 mg/m2, and Alemtuzumab 20 mg IV on day -4 and day -1. GVHD prophylaxis was with cyclosporine (n=13) or tacrolimus (n=14) and full-dose MTX. High-dose viral prophylaxis with valacyclovir 2000 mg QID was given to all recipients from a CMV seropositive recipient/donor pair starting at patient #9, due to a high incidence of CMV reactivation amongst the first 8 patients. Three patients received DLI for disease relapse. Median follow-up for survivors is 13 months (6–26). Results: Of eighteen evaluable patients (3 relapsed, 5 expired, 1 not done) at day 100, 15 had ≥ 95% donor chimerism, and 3 had 90–94% donor chimerism. The cumulative incidence of acute GVHD grade II-IV at day 100 was 4% (95% CI 1–16%), and the cumulative incidence of chronic GVHD at 1 year was 31% (12–52%). Cumulative incidence of non-relapse mortality at day 100 was 18% (7–35%), and at 1 year 31% (14–49%). Cumulative incidence of relapse at 1 year was 28%, resulting in a projected 1-year disease-free survival of 41% (22–60%), and overall survival of 54% (33–71%). Amongst the first eight patients, all (5/5) at-risk recipients developed CMV reactivation. After initiation of prophylaxis with high-dose valacyclovir, 4/11 at-risk recipients developed CMV reactivation. No patient died from CMV disease. TREC analysis in a limited number of patients showed rapid increase in TREC between day 0 and day 180, but no further increment between day 180 and day 365. Conclusions: The use of low-dose alemtuzumab results in low incidences of acute and chronic GVHD. CMV reactivation is common, and can be partially prevented by use of high-dose valacyclovir. Immune reconstitution data on a small subset of patients show limited output of thymic emigrant T cells after 6 months.

Allogeneic Stem Cell Transplantation in Multiple Myeloma: One Center Experience of 86 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3033-3033
Author(s):  
Liisa Volin ◽  
Heli Uotinen ◽  
Eeva Juvonen ◽  
Anne Nihtinen ◽  
Tapani Ruutu
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Related Mortality ◽  
Time Point

Abstract The role of allogeneic stem cell transplantation (SCT) in the treatment of multiple myeloma (MM) is unclear. High transplant-related mortality has been regarded as a particular problem. At the Helsinki University Central Hospital 86 patients with MM have been treated with allogeneic SCT since 1995. The conditioning was at first myeloablative (MA). Since 1999 reduced intensity conditioning (RIC) after autologous SCT has been used in most cases, but a number of young patients with aggressive disease have been transplanted with MA conditioning. Of the patients 42 were male and 44 female. The median age at SCT was 50 (27–64) years. The median number of chemotherapy lines before allogeneic SCT was 1 (range 1–7). Prior autologous SCT had been performed to 55 patients. The median time from diagnosis to allogeneic SCT was 12 (4–168) months, and the time between autologous and allogeneic SCT 6 (2–146) months. At the time of allogeneic SCT 9 patients were in CR, 63 in PR, 4 had stable disease, and 10 progressive disease. 72 patients had a sibling donor: 68 were HLA-identical, one 1 antigen mismatch, 3 identical twins. 14 patients had an HLA-matched unrelated donor. The conditioning was MA in 32 and RIC in 54 patients. The MA conditioning consisted of Cy/TBI in 22, Mel/TBI in 3, and Treosulfan/Fld in 7 patients. RIC was the Seattle protocol (Fld/TBI 2 Gy) in 45, reduced Treosulfan/Fld in 8, and Fld/Cy in 1 patient. 26 patients received a BM graft and 60 patients a PB graft. As GVHD prophylaxis, 18 patients were given CsA/Mtx, 20 CsA/Mtx/MP, 45 CsA/MMF, and 3 nothing (identical twins). The median follow-up time from allogeneic SCT was 39 (2–136) months, 46 (7–136) months for the MA patients and 34 (2–92) months for the RIC patients, respectively. The OS was 50% at 61 months post SCT and there have been no deaths after this time-point. The median PFS was 31 months. After this time-point the disease has progressed in one case, at 90 months. Of the 32 MA patients 16 (50%) and of the 54 RIC patients 22 (41%) have achieved CR after SCT. The cumulative incidence of acute GVHD grade II-IV was 28%. The cumulative incidence of chronic GVHD was 72%, 58% in the MA and 83% in the RIC patients (p=0.074). The incidence of extensive chronic GVHD was significantly (p=0.012) higher in RIC than MA patients, 66% vs. 23%. There were no statistical differences in the incidence of acute or chronic GVHD by donor type (72 siblings/14 unrelated). The cumulative 100-day transplant related mortality was 4.5% and that of the whole follow-up time 14%. 26 patients have died. The cause of death was myeloma in 15, GVHD in 7, and infection in 4 patients. In conclusion, in the present material transplant-related mortality was low and the survival encouraging, supporting the use of allogeneic transplantation with curative aim in selected cases. Developing chemotherapy, given prior to transplantation, may improve the results.

Graft-Vs-Leukemia Effects of Allogeneic Stem Cell Transplantation from HLA-Haploidentical Family Members as Compared to HLA-Identical Sibling Donors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3009-3009
Author(s):  
Hans Jochem Kolb ◽  
Iris Bigalke ◽  
Dominik Termeer ◽  
Susanne Fritsch ◽  
Wolfgang Hill ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Allogeneic Stem Cell Transplantation ◽  
Disease Category ◽  
Haploidentical Transplantation ◽  
Conditioning Treatment

Abstract Allogeneic stem cell transplantation produces a strong graft-versus-leukemia effect which may be enhanced by HLA-mismatches and immune recognition as a result of pregnancy. Therefore we compared the results of HLA-haploidentical transplantation (N=113) to those of HLA-identical sibling (N=195) transplantation performed in the same time. Cases were matched by disease category (acute myeloid leukemia-myelodysplastic syndromes, AML/MDS, acute lymphoid leukemia ALL and lymphoma-chronic lymphocytic leukemia NHL/CLL) and stage of the disease (early, intermediate and advanced). HLA-haploidentical transplants were performed with unmodified bone marrow followed by CD6-depleted mobilized blood stem cells on day 6.; patients with leukemia were in more advanced disease in leukemia, they were younger and more often male. In multivariate analysis survival was influenced by HLA-mismatch, stage of the disease and age of the patient, but conditioning treatment and CMV-seropositivity had no significant effect. Transplant related mortality was influenced by the age of the patient and HLA-match, to a lesser extent by the disease category and the stage, whereas CMV-seropositivity and conditioning had no influence. Remission duration was dependent on the stage of the disease, the donor recipient gender combination and the conditioning treatment in univariate analysis; in multivariate analysis only CMV-seropositivity had a poor prognostic impact. In comparable disease stages the relapse rate was not different in HLA-haploidentical from HLA-identical transplantation as was the rate of acute GVHD. In contrast the rate of chronic GVHD was lower in HLA-haploidentical transplantation. In ALL, relapse rate and remission duration was inferior with non-myeloablative conditioning as compared to myeloablative total body irradiation. In HLA-haploidentical transplantation the response rate of leukemia was better in patients homozygous for the cross reactive HLA-C group given a transplant from a heterozygous donor suggestive of NK activity. This GVL activity was not associated with GVH activity. Similarly maternal donors were superior to paternal donors and female donors in male recipients better than other gender combinations for the control of leukemia without increased GVHD. Non-inherited maternal antigen (NIMA) and inherited paternal antigen (IPA) in the graft-vs-host direction had a weak influence on the relapse rate, but no influence on GVHD. On an observational basis several sons and daughters transplanted with stem cells from the mother had a strong GVL effect without any signs of GVHD. However two have been lost due to untreatable pulmonary complications. Donors with cytotoxic antibodies have been excluded from donation, but cellular reactivity will have to be assessed in more detail. Recent progress in controlling EBV-associated disease by selection of donor T cells without expansion will improve HLA-haploidentical transplantation and show the way to selecting donor with the appropriate immune repertoire including reactivity to leukemia.

Pre-Transplant Predictors and Post-Transplant Sequels of Acute Kidney Injury After Allogeneic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4515-4515
Author(s):  
Yuki Kagoya ◽  
Keisuke Kataoka ◽  
Yasuhito Nannya ◽  
Mineo Kurokawa
Keyword(s):  
Acute Kidney Injury ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Renal Dysfunction ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Kidney Injury ◽  
Post Transplant

Abstract Abstract 4515 Introduction: Acute kidney injury (AKI) is one of the most common complications after allogeneic stem cell transplantation (SCT). Although various post-transplant risk factors for AKI have been reported, there have been few studies which comprehensively assessed pre-transplant comorbidities and investigated their impact on the occurrence of AKI. Methods: We performed a retrospective analysis of 207 consecutive adult patients undergoing myeloablative or non-myeloablative SCT between 2001 and 2009. Cumulative incidence of AKI during the first 100 days was analyzed. AKI was defined and classified according to Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) criteria. Renal dysfunction considered to be associated with multiple organ dysfunction syndromes before death was excluded. The time to the development of severe AKI (defined as RIFLE class I or class F) was calculated and the multivariate analysis of pre- and post-transplant variables was performed by a Cox proportional hazards model. Post-transplant factors were assessed as time-dependent variables. As a representative of pre-transplant comorbidities, we used the hematopoietic cell transplantation-specific comorbidity index (HCT-CI). To analyze the outcomes of patients who developed AKI, the multivariate analysis of OS and NRM was carried out by a landmark approach, in which the follow-up was started at the onset of AKI class R or severe AKI in patients who developed AKI class R or severe AKI, and at the median time of the incidence of AKI in patients who did not develop AKI. Results: Among 207 patients, myeloablative SCT was performed in 149 patients and non-myeloablative SCT in 58 patients. Overall, 158 patients (76.3%) developed AKI, and 92 patients (44.4%) developed severe AKI. The median interval to the occurrence of severe AKI was 30 days after SCT. The cumulative incidence of severe AKI within 100 days in patients with a HCT-CI score 0, 1–2, and ≥3 was 21.3 %, 48.8%, and 73.9%, respectively. In a multivariate analysis, the HCT-CI was independently and most strongly associated with severe AKI (HCT-CI 1–2: adjusted hazard ratio [HR] 2.42, P<0.01; HCT-CI ≥3: adjusted HR 4.69, P<0.01), although no patients had renal dysfunction defined by the HCT-CI scoring system (pre-transplant creatinine > 2.0 mg/dl) before SCT in our cohort. Among post-transplant factors, sepsis (HR 2.66, P<0.01) and use of vancomycin (HR 1.79, P=0.04) were significantly associated with the development of severe AKI. In total, 101 of 207 patients (48.8%) died, of which 52 patients (51.5%) died of non-relapse causes. In a landmark analysis, the 3-year OS was 61.4% in patients without AKI, 53.9% in patients with AKI class R, and 39.3% in patients with severe AKI (P<0.01). The 3-year NRM was 5.6% in patients without AKI, 16.6% in patients with AKI class R, and 40.8% in patients with severe AKI (P<0.01). Multivariate analysis showed that severe AKI was a significant risk factor for worse OS (HR: 2.10, P=0.01) and NRM (HR: 6.15, P<0.01), while the occurrence of AKI class R did not have a strong impact on OS (HR: 1.14, P=0.69) or NRM (HR: 2.31, P=0.20). According to the cause of death, 24 patients died of severe AKI within 100 days after SCT, consisting of 2 on-disease patients (8.3% of the 24 patients who relapsed within 100 days after SCT) and 22 patients in remission (12.0% of the 183 patients who did not relapse within 100 days after SCT). There was no significant difference in the proportions of severe AKI as a mortality cause between patients with or without relapse (P=1.0). Conclusions: We found that high HCT-CI scores, particularly ≥3, were the most important pre-transplant predictor of severe AKI. The development of severe AKI within the first 100 days after SCT was independently associated with worse prognosis, irrespective of the status of the primary disease. Therefore, the strategy to prevent the occurrence of life-threatening severe AKI in patients with a high HCT-CI score would be imperative to improve their survival after allogeneic SCT. Disclosures: No relevant conflicts of interest to declare.

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