Allogeneic Stem Cell Transplantation (alloSCT) and Donor Lymphocyte Infusion (DLI) In Patients with Non-Hodgkin Lymphoma (NHL) Who Experienced Relapse or Progression After Autologous Stem Cell Transplantation (autoSCT): Retrospective Analysis From the Korean Society of Blood and Marrow Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3536-3536 ◽  
Author(s):  
Ji-Won Kim ◽  
Byung-Su Kim ◽  
Soo-Mee Bang ◽  
Inho Kim ◽  
Dong Hwan Kim ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Serum Albumin ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Grade 3 ◽  
Ecog Ps ◽  
Significant Factors

Abstract Abstract 3536 Prognosis of patients with NHL who underwent relapse or progression after autoSCT is generally dismal and treatment option is limited. AlloSCT has been performed to overcome this problem and long term survivors have been reported. However, substantial transplant-related mortality (TRM) is a significant problem. We report clinical outcomes of alloSCT in these patients and DLI after failure of alloSCT along with analysis of risk factors for treatment results and adverse events. This retrospective study was performed in 7 hospitals in Korea. Candidate risk factors were age, sex, histology, Ann Arbor stage at diagnosis, number of prior treatments, time to progression (TTP) after autoSCT, bone marrow involvement, Eastern Cooperative Oncology Group (ECOG) performance status (PS), donor type, stem cell source, conditioning regimens of alloSCT, serum lactate dehydrogenase (above 250 IU/L), serum albumin (above 3.0 g/dL), and acute graft-versus-host disease (aGvHD). Between August 1998 and March 2009, 38 patients received alloSCT. Median age was 37 (range, 17–54) years. Male to female ratio was 26:12. Eighteen patients (47.4%) had B-cell lymphoma and 20 patients (52.6%), T/NK-cell lymphoma. Before alloSCT, patients had received median 4 (range, 2–7) prior treatments including autoSCT. Median TTP after autoSCT was 5.9 (range, 0.8–35.8) months. Twenty four patients (63.2%) received stem cells from related donors and 14 patients (36.8%) from unrelated donors. Median number of CD34+ cells infused was 5.41 × 106 (range, 0.86 × 106-16.60 × 106) /kg. Eighteen patients (47.4%) underwent a myeloablative conditioning and 20 patients (52.6%), a reduced intensity conditioning. During a median follow-up of 45.2 (range, 1.3–137.1) months, 24 patients (63.2%) experienced treatment failure and 22 patients (57.9%) died. Median event-free survival (EFS) was 6.3 (95% confidence interval (CI), 4.3–8.4) months. Median overall survival (OS) was 19.0 (95% CI, 3.8–34.2) months. Estimated 5-year survival rate was 35.0% (Figure). Treatment response was evaluable in 30 patients. Response rate was 73.3%; complete remission (CR) was achieved in 20 patients (66.7%) and partial response in 2 patients (6.7%). Grade 3 or 4 renal toxicity developed in 6 patients (15.8%), grade 3 or 4 hepatic toxicity in 15 patients (39.5%) including veno-occlusive disease (VOD) in 6 patients (15.8%), aGvHD in 13 patients (34.2%), and neutropenic fever in 34 patients (89.5%) including documented sepsis in 11 patients (28.9%). TRM was reported in 8 patients (21.1%). Causes of TRM were infection in 7 patients and VOD in 1 patient. In univariate analysis, no significant association was found with treatment response. By contrast, EFS was related to stage (p=0.039), TTP after autoSCT (p=0.033), and PS (p<0.001). OS was associated with stage (p=0.037), number of prior treatments (p=0.049), TTP after autoSCT (p=0.032), PS (p<0.001), and serum albumin (p=0.016). On the other hand, aGvHD was not associated with EFS (p=0.545) and OS (p=0.476). Multivariate analysis demonstrated that stage IV (hazard ratio (HR) 2.85 (95% CI, 1.13–7.22); p=0.027) and ECOG PS 2 (HR 3.94 (95% CI, 2.08–7.47); p<0.001) were significant factors for EFS and that stage IV (HR 3.28 (95% CI, 1.19–9.04); p=0.022), ECOG PS 2 (HR 5.26 (95% CI, 2.22–12.48); p<0.001), and serum albumin above 3.0 g/dL (HR 0.15 (95% CI, 0.03–0.63); p=0.010) were significant factors for OS. TRM was associated with PS (p=0.010) and serum albumin (p=0.040) by univariate analysis. Multivariate analysis showed that ECOG PS 2 was the only significant factor for TRM (relative risk (RR) 11.77 (95% CI, 1.43–97.01); p=0.022). ECOG PS 2 was also a significant factor for documented sepsis (RR 7.14 (95% CI, 1.08–47.42); p=0.042). DLI was performed in 8 patients who failed alloSCT. After median 1.5 (range, 1–6) cycles of DLI, 2 patients achieved CR. Grade III or IV aGvHD developed in these patients. By contrast, among 6 patients who failed to achieve CR, aGvHD developed in 2 patients. In conclusion, alloSCT is a viable option for patients with NHL who failed autoSCT despite high TRM. Stage and PS were significant factors for EFS and OS. Serum albumin was a significant factor for OS. In patients with ECOG PS 2, alloSCT should be avoided and novel treatment approaches should be offered due to high risk of TRM. DLI after failure of alloSCT showed promising results, which supports the presence of graft-versus-lymphoma effect. Disclosures: No relevant conflicts of interest to declare.

Donor Selection For Haploidentical Hematopoietic Stem Cell Transplantation: Who Is The Better – Donor-Recipient Risk Factor Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 705-705
Author(s):  
Yu Wang ◽  
Xiao Jun Huang
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Risk Factor ◽  
Stem Cell ◽  
Lower Incidence ◽  
Family Relationship ◽  
Donor Age ◽  
Sibling Donor ◽  
The Difference ◽  
Grade 3

Abstract Background many aspects should be considered when selecting an ideal donor. The progress made in haploidentical HSCT in recent years offers almost unlimited donor and availabilities of more than one donor at many occasions. To date, there have been no studies to answer the question of apart from HLA disparity, whether one donor should be preferred over another among various haploidentical donors available. The goal of the current study was to attempt to answer the question by analyzing the data on haploidentical HSCT without in-vitro T cell depletion modality. Methods Consecutive patients with leukemia or MDS who received HSCT from 3-5 of 6 HLA loci-matched family donors excluding collateral relatives between May 2002 and December 2010 were enrolled in this study (n=749). The stem cell source was G-CSF mobilized BM combined with PB. The conditioning regimen was modified BUCY plus ATG with 10mg/kg in total dosage. Patients receiving prophylactic DLI for prevention of leukemia relapse were excluded. Donor-recipient risk factors relevant to selection of optimal donor for haploidentical HCT were analyzed. Results (1)donor sex: male donor had lower incidence of both grade 2-4 (39% vs. 46%, p=.07) and grade 3-4 acute GVHD (aGVHD) (11% vs. 17%, p=.04), lower rate of NRM (16% vs. 24%, p=.006) and higher probabilities of OS (70% vs. 62%, p=.02) and LFS (67% vs. 60%, p=.03), compared with female donor. In multivariate analysis, donor sex was still a risk factor for GVHD, NRM and survival. However, if mother donor was excluded, all the difference became no longer significant. (2) Donor age: donor younger than 30 years old had lower incidence of both grade 2-4 (25% vs. 48%, p<.0001) and grade 3-4 aGVHD (5% vs. 16%, p=.0005), lower rate of NRM (12% vs. 22%, p=.007) and higher probabilities of OS (78% vs. 64%, p=.001) and LFS (76% vs. 64%, p=.002), compared with donor older than 30 years old. In multivariate analysis, donor age was a more prominent risk factor for GVHD, NRM and survival compared with donor sex. And if mother donor was excluded, all the difference remained significant both in univariate and multivariate analysis. (3)The rate of GVHD was not associated with the extent of HLA disparity or any individual allele disparity. (4) comparison between mother and father: father donor had lower incidence of both grade 2-4 (45% vs. 56%, p=.03) and grade 3-4 aGVHD (13% vs. 22%, p=.007), lower rate of NRM (14% vs. 26%, p=.003) and higher probabilities of OS (70% vs. 57%, p=.007) and LFS (67% vs. 57%, p=.03), compared with mother donor. In multivariate analysis, mother donor was still a risk factor for GVHD, NRM and survival. (5) comparison between offspring and sibling: offspring donor had significant lower incidence of grade 2-4 aGVHD (16% vs. 37%, p=.002), lower NRM and higher survival, although not reaching statistical significance, compared with sibling donor. In multivariate analysis, sibling donor was still a risk factor for GVHD. (6) comparison among sibling and father donors: donor older than 30 years old was the most important risk factor affecting GVHD, NRM and survival while the rates between father and sibling donor were comparable. Conclusions Not abiding by the rule of HLA disparity, this study was the first one to confirm that significant different outcomes were achieved among various haploidentical donors and proved once again that haploidentical HSCT overcame HLA barriers. Instead of HLA disparity, donor age and the family relationship were important risk factors under our treatment modality. The underlying mechanisms of crossing human leukocyte antigen barriers need further investigation and to be validated by other treatment modalities. Figure impact of donor age and family relationship on GVHD This work was partly supported by The Key Program of National Natural Science Foundation of China (Grant No. 81230013), Beijing Municipal Science & Technology Commission (No.Z121107002812033) and Beijing Municipal Science & Technology Commission(No. Z121107002612035). Disclosures: No relevant conflicts of interest to declare.

Antithymocyte Globulins (ATG) as Part of the Myeloablative Conditioning (MAC) Regimen Can Reduce the Risk of Severe Graft-Vs.-Host Disease (GVHD) after Allogeneic Stem Cell Transplantation (allo-SCT) from Matched-Unrelated Donors (MUD).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1151-1151
Author(s):  
Mohamad Mohty ◽  
Marie- Lorraine Balere ◽  
Gerard Socie ◽  
Noel-Jean Milpied ◽  
Norbert Ifrah ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Beneficial Effect ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Hla Typing ◽  
High Dose ◽  
Increased Risk ◽  
Grade 3

Abstract The use of ATG in the setting of standard MAC allo-SCT is still controversial. Some studies, however, suggested a beneficial effect of ATG in preventing acute GVHD. Here, we report the results of a large multicenter retrospective study analyzing the effect of ATG, incorporated within the MAC regimen for MUD-transplants in leukemic patients compared to patients not receiving ATG. The purpose of the study was to compare the incidence and severity of acute and chronic GVHD as well as non-relapse mortality (NRM), leukemiafree and overall survivals (LFS, OS). The study included 171 adult patients with acute leukemia and MDS (73% standard risk and 27% more advanced disease) reported to the registry of the SFGM-TC between 1998 and 2004, and for whom detailed allelic HLA typing (4 digits) for the recipient and the donor was available. Patients’ characteristics were as follow: median age: 33 (range, 15–67), 57% male recipients, 35% female donors, 44% AML, 43% ALL, 11% MDS and 2% unclassified leukemia. The stem cell source was bone marrow in 72.5% of patients, while PBSCs were used in 27.5% of cases. 81% of patients were transplanted from 10/10 allelic MUD, and 19% from a MUD with at least one allelic difference. A high dose TBI-based MAC regimen was used in 84% of cases, while 16% received a high-dose chemotherapy containing MAC regimen. 85% of the patients received the classical CsA and short course methotrexate GVHD prophylaxis regimen. In this series, 120 patients (70%) did not receive ATG (“no-ATG” group), while 51 patients received ATG (“ATG” group; Thymoglobuline*-Genzyme in all cases; total ATG dose: ≤5 mg/Kg, n=13; &gt;5 and &lt;10 mg/Kg, n=17; ≥10 mg/Kg, n=21) as part of the MAC regimen. Except for a significantly higher number of allelic differences between recipient and donor (33% vs. 13%; P=0.002), the “no-ATG” and “ATG” groups were strictly comparable as for patients, disease and transplant characteristics. 95% of patients had a sustained engraftment at a median of 20 (range, 9–41) days after allo-SCT with no significant differences between the 2 groups. With a median followup of 30.3 (range, 2.6–68.1) months after allo-SCT, grade 0–1 and 2–4 acute GVHD occurred in 74 (46%) and 88 patients (54%) respectively, with grade 3–4 acute GVHD being significantly lower in the “ATG” group as compared to the “no-ATG” group (18% vs. 32%; P=0.04). In this series, 142 patients (83%) were evaluable for chronic GVHD. Limited and extensive chronic GVHD were observed in 22 and 25% of assessable patients respectively, with extensive chronic GVHD being significantly lower in the “ATG” group as compared to the “no-ATG” group (5% vs. 33%; P=0.001). Interestingly, patients from the “ATG” group had a higher incidence of limited chronic GVHD (33% vs. 18%; P=0.06). The use of ATG was not associated with a higher risk of infections: infection-related mortality was comparable between both groups (23% vs. 27%, P=NS). Also, NRM was comparable between both groups (30% vs. 29%; P=NS). In multivariate analysis including all relevant risk factors tested in the univariate analysis, we found that an HLA allelic mismatch and the non-use of ATG were associated with an increased risk of severe grade 3–4 acute GVHD (RR=2.80, 95%CI, 1.5–5.3), P=0.001; and RR=2.4, 95%CI, 1.1–5.0, P=0.02 respectively). Similarly, multivariate analysis showed that the absence of use of ATG was the unique and strongest parameter associated with an increased risk of extensive chronic GVHD (RR=6.9; 95%CI, 1.7–29.0, P=0.008). Finally, LFS and OS at 2 years were not significantly different between the “no-ATG” and “ATG” group (48.8% vs. 41.3%, P=NS; and 53.6% vs. 54.3%, P=NS; respectively) Despite its retrospective nature, these results strongly indicate a global long-term beneficial effect of ATG when used as part of the MAC regimen prior to allo-SCT from MUD (especially in the HLA mismatch setting). Though prospective studies are needed to assess the optimal ATG dosing and administration schedule, such protective effect of ATG against severe acute and chronic GVHD, can be likely achieved without an increased risk of infections or leukemia recurrence.

LACE - an Effective Conditioning Regimen for Lymphoma Patients Undergoing Autologous Transplant- Analysis of Outcomes and Prognostic Factors

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3979-3979
Author(s):  
Deepan Rajamanickam ◽  
Anant Gokarn ◽  
Alok Gupta ◽  
Sachin Punatar ◽  
Ravi Thippeswamy ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Median Duration ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Salvage Chemotherapy ◽  
Pet Ct ◽  
First Relapse ◽  
Grade 3

Abstract Background: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed and refractory lymphomas. BEAM (BCNU, etoposide, cytarabine, melphalan) and CBV (cyclophosphamide, BCNU , VP-16) are most widely used conditioning regimens prior to ASCT in lymphomas. LACE has been found to be an effective regimen though outcome data is sparse.As BCNU was difficult to procure in India, we began using this regimen since November 2007. This study is a retrospective analysis to evaluate outcomes and possible prognostic factors in this cohort of patients. Methods: All patients between November 2007- January 2014 who received LACE regimen for primary progressive, chemotherapy sensitive relapse or relapsed-refractory Hodgkin’s (HL) and non- Hodgkin’s lymphoma (NHL) were included.Patients received salvage chemotherapy with either GDP, ICE, MINE or DHAP with or without rituximab (NHL patients). PET-CT was performed in all patients after 2-3 cycles of salvage chemotherapy. Response assessment was performed according to Cheson’s criteria. Patients underwent peripheral blood stem cell collection after 3rd or 4th cycle of salvage chemotherapy.Conditioning regimen used was LACE (lomustine-200 mg/m2 d-7, etoposide 1000mg/m2 d-7, ara-c 2000 mg/m2 d-6, d-5 and cyclophosphamide 1800 mg/m2 d-4 to d-2). PET-CT was done on day 100, 1 year post transplant and then yearly for next 4 years. Incidence and grade of treatment related toxicity was recorded according to CTCAE V-3. Prognostic factors evaluated for overall survival (OS) and progression-free survival (PFS) included time between diagnosis – transplant; time between CR1 - first relapse; baseline, presalvage and pretransplant serum albumin,LDH and B2 microglobulin; PET positivity pretransplant, at day 100 and day 360; remission status at time of transplant; IPI (NHL) and IPS (HL) at baseline and at relapse; stage at diagnosis and at relapse. Probabilities of OS and PFS were estimated using the Kaplan–Meier method. Univariate comparisons of survival times for potential prognostic factors were made using the log-rank test. Multivariate analysis of significant factors was performed by Cox –regression analysis. Results: Seventy patients had HL while 30 NHL (Male-73, Female-27) with median age at transplant of 23 years. In NHL cohort, 19 were DLBCL, 6 were T-cell lymphomas, 4 mantle cell lymphoma and 1 Burkitt’s lymphoma.The median time from complete remission (CR) to first relapse and time from diagnosis to transplant were 1.4 and 1.9 years respectively. The median number of lines of chemotherapy pre transplant was 2. GDP (53 patients) was the most commonly used salvage chemotherapy. At the time of transplant, 68% were in CR, 29% in partial remission (PR) and 3% had refractory state. The incidence of grade 3-4 oral mucositis was 8% with a median duration of 3.5 days. The incidence of grade 3-4 diarrhea was 4% with median duration of 3 days. Median days to myeloid and platelet engraftment were 10 and 13 respectively. The median follow-up was 2.9 years. The probability of OS and PFS at 5 years was 67% and 57% for the whole group, 73% and 62% in HL group and 51% and 46% in NHL group. Seven patients died due to transplant related causes which included 6 due to sepsis and 1 due to herpes simplex encephalitis. In univariate analysis for OS, PET negativity pre transplant (P= 0.03), at day 100 (P= 0.019) and at day 360 (P= 0.01) were associated with better OS. Similarly, HL patients with IPS 0-2 (P=0.002) at time of relapse had better OS. Univariate analysis for PFS showed that PET negativity pre transplant (P=0.002), at day 100 (P= 0.0001) and at day 360 (P=0.00) was associated with better PFS. HL patients with IPS 0-2 (P=0.000) and NHL patients with IPI 0-2 at time of relapse (P=0.007) had better PFS. Patients in CR at the time of transplant had better PFS than those in not in CR (P=0.008). Overall HL patients had better OS (P=0.037) and PFS (P=0.097) compared to NHL group. Multivariate analysis for OS (P= 0.021) and PFS (P=0.001) revealed PET negativity at day 100 as the only significant prognostic factor. Conclusions: This is the largest reported cohort of lymphoma patients transplanted with LACE regimen. LACE is effective and well tolerated conditioning regimen in lymphoma transplant. PET negativity at various time points pre and post transplant prognosticates for better survival. Disclosures No relevant conflicts of interest to declare.

Risk Factor of Hepatic Veno-Occlusive Disease: Analysis of Clinical Data of 5024 Patients Extracted from the Database of the Japan Marrow Donor Program.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2970-2970
Author(s):  
Miwa Sakai ◽  
Kazuteru Ohashi ◽  
Takuya Yamashita ◽  
Hideki Akiyama ◽  
Hisashi Sakamaki
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Clinical Data ◽  
Univariate Analysis ◽  
Disease Status ◽  
Occlusive Disease ◽  
Blood Type ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Hepatic veno-occlusive disease (VOD) is one of the most serious complication of hematopoietic stem cell transplantation (HSCT). Various factors have been identified as increasing the risk of hepatic VOD, but few of them have been associated with a significantly increased risk. We retrospectively analyzed the clinical data of 5024 transplant recipients (median age28, range 0–68) which extracted from the Japan Marrow Donar Program. The diagnosis of VOD was made according to the McDonald’s criteria, and 324 out of 4833 patients (6.7%) were eventually diagnosed with VOD. The possible risk factors based on the previous studies were counted on an initial univariate analysis, and cumulated significant factors were further analyzed for their potential value for VOD development in multivariate analysis. Variables correlated with an increased risk of VOD were: time of transplant >2 times (relative risk (RR) 2.7; p=0.006), pretransplant disease status (RR 2.3; p=0.000), prior liver disease (RR 2.1; p=0.017), ABO blood type mismatch (RR1.7; p=0.000). In patients receiving either busulfan or melphalan for conditioning increased VOD risk (RR 1.5 and 1.8; p=0.007 and 0.002, respectively). In our multivariate analysis, stem cell source, and prophylactic use of heparin and Ursodiol had no significant effect on VOD development. This analysis might contribute to revise the previously reported risk factors for VOD and the data could be used to know which patients might be suitable subjects for new trials for VOD prevention.

High-Dose Cytarabine Consolidation (≥1.5 g/m2) Might Have Shown a Better Outcomes Than Intermediate-Dose Cytarabine (1.0 g/m2) Combined With Anthracyclines In AML Patients Who Had Achieved Complete Remissions In The First Induction by Standard 3+7 Regimen

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2692-2692 ◽  
Author(s):  
Yong Park ◽  
Ga-won Kang ◽  
Dae Sik Kim ◽  
Suk-young Lee ◽  
Se Ryeon Lee ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Univariate Analysis ◽  
High Dose ◽  
Inclusion Criteria ◽  
High Dose Cytarabine ◽  
Intermediate Dose ◽  
Significant Factors

Abstract Purpose Based on CALGB trial in 1994, 3-4 cycles of high-dose cytarabine have been one of the standard consolidation therapies. Despite the confirmed efficacy of anthracyclines for remission induction, the role of anthracyclines for postremission consolidation is a subject still under debate. In this retrospective analysis, we compared the efficacy of high-dose cytarabine (>=1.5 g/m2) and intermediate-dose cytarabine (1 g/m2) combined with anthracyclines as postremission therapy. Methods The patients enrolled in the Korea University AML registry from September 2002 to August 2011 were analyzed. Inclusion criteria were as follows; 1) Complete remission was achieved in first induction by standard 3+7 regimen (idarubicin 12 mg/m2 or daunorubicin 45 or 60 or 90 mg/m2 on D1-3 + cytarabine 100 mg/m2 on D1-7) 2) Postremission therapy was performed for 3-4 cycles by one of the following regimen; Arm A (high-dose cytarabine): cytarabine 3 g/m2 for patients =< 60 years old or 1.5 g/m2 for patients > 60 years old, q 12 hours on D1, 3, 5. Arm B (intermediate-dose cytarabine combined with anthracyclines): cytarabine 1.0 g/m2 q 12 hours on D1-3 combined with mitoxantrone or idarubicin 12 mg/m2 on D1,2. Univariate and multivariate analysis for survival were performed by Kaplan-Meier and Cox-regression analysis, respectively. Results Among 172 AML patients enrolled in the registry, 95 patients (55%) were satisfactory for inclusion criteria. The number of arm A and B was 51 and 44, respectively. Some patients (N=47) with intermediate or high-risk cytogenetics have undergone autologous or allogeneic stem cell transplantation. Univariate analysis for relapse-free survival (RFS) demonstrated that age (=< 60 vs. >60, p=0.007), stem cell transplantation (p=0.001), and consolidation regimen (Arm A vs. Arm B, p=0.007) were statistically significant. The median RFS of arm A was not reached and significantly superior to that of arm B (14.0 months, 95% CI 8.5 months to 19.5 months) (Figure 1). Multivariate analysis showed that stem cell transplantation (HR 0.384, 95% CI 0.195 to 0.758, p=0.06) and consolidation regimen (HR 0.454, 95% CI 0.237 to 0.872, p=0.018) were independently significant factors for RFS. With regard to overall survival (OS), age (p<0.001), performance status (ECOG 0,1 vs. 2,3, p<0.001), WBC count at diagnosis (<20000/μL vs. >=20000/μL, p=0.033), WHO classification (de novo vs. secondary, p=0.05), stem cell transplantation (p=0.001), and consolidation regimen (p=0.007) were statistically significant by univariate analysis. The median OS of arm A was also not reached and significantly superior to that of arm B (18.1 months, 95% CI 7.7 months to 28.5j months) (Figure 2). Multivariate analysis for OS showed that age (HR 0.482, 95% CI 0.248 to 0.939, p=0.032), stem cell transplantation (HR 0.469, 95% CI 0.244 to 0.899, p=0.023), and consolidation regimen (HR 0.474, 95% CI 0.252 to 0.894, p=0.021) were independently significant factors. There was no statistical significance in treatment-related mortality between arm A and arm B (7% and 4%, respectively, p=0.541). Conclusions This analysis showed that as compared with intermediate-dose cytarabine (1.0 g/m2) combined with anthracyclines, high-dose cytarabine consolidation (>=1.5 g/m2) was independently favorable factor for both RFS and OS in AML patients who had achieved complete remissions in first induction by standard 3+7 regimen. Based on this study, we hypothesize that the addition of anthracycline during consolidation might have a limited value as compared with cytarabine intensification. The confirmatory prospective trial should be required. Disclosures: No relevant conflicts of interest to declare.

Risk Factors Predicting Outcomes for Primary Refractory Hodgkin Lymphoma Patients Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 520-520 ◽  
Author(s):  
Gunjan L Shah ◽  
Kurt S Bantilan ◽  
Stephanie L Verwys ◽  
Susan J McCall ◽  
Joachim Yahalom ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Salvage Therapy ◽  
Research Funding ◽  
Stage Iv ◽  
Salvage Chemotherapy ◽  
Stage Iv Disease

Abstract Introduction: Limited information exists on the best treatment strategy for Primary Refractory (ref) Hodgkin Lymphoma (HL). For the past 20 years, we have treated patients (pts) on sequential ifosfamide, carboplatin, etoposide (ICE)-based clinical trials with the intent to undergo high dose therapy (HDT) and autologous stem cell transplantation (ASCT). As previously reported (Moskowitz, Blood 2010) and confirmed by other centers, a negative PET scan prior to ASCT predicts for marked improvement in outcome in pts with relapsed HL. We aimed to identify risk factors that predict PET response to salvage chemotherapy in ref HL and evaluate outcomes following HDT and ASCT in this patient population. Methods: From 10/1/94 to 7/10/15, 192 ref HL pts were treated on sequential trials at MSKCC. Demographic and clinical factors were collected. Event free survival (EFS) and overall survival (OS) were calculated from the date of histologic confirmation of ref disease, estimated by Kaplan-Meier method, and compared by the log rank test. Events included relapse or death. Cox regression was used for the multivariate regression model. Patients were selected to receive a radiation-based conditioning regimen if all sites of nodal disease could be encompassed into a radiation field. Results: Patient characteristics included a median age of 31 (range 14-79) with 54% female. B symptoms, extranodal disease, stage IV disease, and disease bulk > 5cm were present in 31%, 48%, 44%, 40%, respectively. In the intent-to-treat (ITT) population, 41% had a positive post-salvage PET scan. As analyzed by ITT, median EFS was 8.9 years with a median OS of 10.4 years. On multivariate analysis, the presence of B symptoms and bulk >5cm at documentation of ref disease predicted for a reduced chance of achieving a negative PET after salvage therapy, with an odds ratio (OR) of 2.03 for B symptoms and 2.13 for bulk >5cm. For the 169 (88%) transplanted patients, 68% had a negative pre-ASCT PET. Radiation based conditioning was used for 70% of the pts. Median EFS was 12.8 yrs and median OS was not reached with a median follow-up of 3.6 yrs (range, 0.55 to 18.04 yrs) for the surviving patients (Figure 1). On multivariate analysis, both stage (IV vs I-III) and persistent PET abnormality pre- ASCT correlated with a shorter EFS. A risk stratification model was created and pts could be divided into 4 groups. 1) stage I-III disease and a negative PET pre-ASCT, the median EFS was not reached; 2) stage I-III disease and a positive PET pre-ASCT scan-the OR of an event was 4.04 (95% CI 1.93 to 8.45) with the median EFS not reached, 3) Stage IV disease and a negative PET pre-ASCT, the OR was 3.78 (95% CI 1.64 - 8.74) with a median EFS of 8.9 yrs, 4) Stage IV disease and a positive PET pre-ASCT, the OR was 8.22 (95% CI 3.99 to 16.94) with a median EFS of 0.9 yrs (Figure 2). Conclusions: B symptoms and bulk >5cm predicted for residual PET avidity after salvage therapy in ref HL. Persistent PET abnormality pre-ASCT and stage were risk factors for earlier relapse and death and can be used to prognosticate survival. Further studies are needed to determine optimal therapy for patients with multiple risk factors. Figure 1. EFS for the Transplanted Patients Figure 1. EFS for the Transplanted Patients Figure 2. EFS for the transplanted pts based on the presence of risk factors (PET avidity pre-HSCT and Stage) Figure 2. EFS for the transplanted pts based on the presence of risk factors (PET avidity pre-HSCT and Stage) Disclosures Moskowitz: GSK: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding.

Multiple Extranodal Involvements; Significant Risk Factor of Relapse In Peripheral T-Cell Lymphoma, Not Otherwise Specified

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4887-4887
Author(s):  
Kazuya Sato ◽  
Yoshihiro Torimoto ◽  
Yutaka Kohgo ◽  
Takashi Fukuhara
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Risk Groups ◽  
Primary Treatment ◽  
Extranodal Involvement ◽  
Peripheral T Cell Lymphoma ◽  
Bulky Disease ◽  
Not Otherwise Specified

Abstract Abstract 4887 Background: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) comprises clinically and histopathologically a heterogeneous group of predominantly nodal diseases which do not fit into definition of any other identified subtype of PTCLs. Most of cases are advanced diseases and characterized by aggressive behavior and very poor prognosis. Although several risk factors for response and survival in PTCL-NOS have been reported, little information is available for the incidence and risk factors of relapse after complete response (CR) achievement. Further analyses of the relapse will give valuable information for effective therapeutic strategies for PTCL-NOS. The aim of this study is to evaluate the incidence and risk factors of the relapse in PTCL-NOS patients. Methods: We retrospectively reviewed 107 patients with PTCL-NOS diagnosed by The 4th edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues in Hokkaido Hematology Study Group, which includes 30 hematology/oncology or pediatrics departments of 23 institutes, from January 2002 to December 2009. We further investigated the incidence, clinical backgrounds, and risk factors of relapse of the PTCL-NOS patients. Response to treatment was assessed by international workshop to standardize response criteria for non-Hodgkin's lymphomas (Cheson BD et al. J Clin Oncol. 1999). Overall survival (OS) curves were estimated using Kaplan-Meier method and compared by log-rank test. The association between clinical factors and relapse rate was evaluated in univariate analysis by the chi-squared test. Factors independently associated with relapse or OS were identified in multivariate analysis by logistic regression model or Cox proportional hazards model, respectively. Results: The median follow-up of the patients was 24 months (range 1–95). The sample population included 70 males and 37 females with a median age of 67 years (range 9–94). Chemotherapy (ChT) was selected in 90% (96/107) patients as the primary treatment. CHOP-lile regemens were chosen in 91% (86/96) patients as the primary ChT. The estimated 5 year-OS of all the patients was 35%. 48 (52%) patients achieved CR after primary treatment in the evaluable 92 patients, and were futher analyzed. Relapse was occured in 46% (22/48) patients with a median remission duration of 9 months (range 2–51). Multiple or diffuse extranodal relapses were presented in 64% (14/22) patients. Only 5 (24%) paitients achived 2nd CR in the 21 relapsed patients recived salvage ChT. Survaval of patients with relapse was significantly shorter than that without relapse (5 year-estimated OS 32% vs 100%, p<0.0001). Factors of high relapse rates at diagnosis were as follows; central nervous system involvement (100%), extranodal involvement sites>1 (87%), gastrointestinal involvement (80%), bulky disease (67%), bone marrow (BM) involvement (67%), high (H) and high-intermediate (HI) risk groups of International Prognositic Index (IPI) (63%). In addition, relapse rate of the patients showing FDG-uptake by PET after primary treatment was 100%. In univariate analysis, extranodal involvement sites at diagnosis >1 (p=0.022), H and HI risk groups of IPI at diagnosis (p=0.021), FDG-uptake by PET after primary treatment (p=0.043) were identified as risk factors of relapse. Age, clinical stage, B-sympton, perfomance status, BM imvolvement, bulky disease, high LDH level, risk groups of prognositic index for PTCL-U (PIT), and regemen or dose-reduction of primary treatment were not significant indicators for relapse in univariate analysis. In multivariate analysis, extranodal involvement sites at diagnosis >1 was identified as an independent risk factor not only for relapse (relative risk 26.0; 95% CI 1.115–605.9; p=0.043) but also for OS (relative risk 10.8; 95% CI 1.1466–80.13; p=0.02). Conclusions: Almost half of PTCL-NOS patients who achieved CR after primary treatment will relapse and the prognosis is poor. Multiple extranodal involvements at diagnosis will be a predictive factor of relapse and survival. These findings warrant further studies regarding specific treatment approaches for PTCL-NOS patients with multiple extranodal involvements to inhibit the relapse. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Extramedullary Relapses after Allogeneic Stem Cell Transplant (allo-SCT) in Adult Patients with Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5690-5690
Author(s):  
Hiroaki Shimizu ◽  
Takuma Ishizaki ◽  
Nahoko Hatsumi ◽  
Satoru Takada ◽  
Akihiko Yokohama ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Risk Factor ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Independent Risk Factor ◽  
Univariate Analysis ◽  
Adult Patients ◽  
Age At Diagnosis ◽  
Cell Transplant

Background: Extramedullary (EM) relapses were sometimes observed in acute leukemia patients both after chemotherapy and allo-SCT. Our recent study described that the rate of EM relapses after allo-SCT was significantly higher when comparing with that after chemotherapy in acute myeloid leukemia (AML) patients. Since more potent graft-versus-leukemia (GVL) effect in EM lesion than bone marrow (BM) is proposed as potential biological basis of this phenomenon, it is expected that EM relapses after allo-SCT more frequently occurred than after chemotherapy also in ALL patients. However, this hypothesis has not been examined, and risk factors of EM relapses after allo-SCT have not been elucidated. So, we conducted this retrospective study to address this unsolved issue. Patients and methods: The study population included in this study was 215 adult patients who were diagnosed as ALL between 1990 and 2017 and received intensive chemotherapy. In the first part of this study, to compare the rates of EM relapses between after chemotherapy and allo-SCT, the initial relapses of the 88 patients were analyzed. In the second part, to investigate risk factors for EM relapses after allo-SCT, 110 patients who underwent allo-SCT against ALL were analyzed. EM relapses included both one only in EM lesions and in concurrent EM and BM lesions. Fisher's exact test was used to compare binary variables. Cumulative incidences (CIs) of EM relapse were compared using the stratified Gray test, considering relapse without EM lesions and death without the event as a competing risk. The logistic regression model and the Fine-Gray proportional hazard model were used for multivariate analysis of risk factors of EM relapses among the initial relapses and after allo-SCT, respectively. Values of p < 0.05 were considered significant. Results: Of the 88 relapsed patients included in the first part of this study, the median age at diagnosis was 47 years (range, 15-79 years), and the median duration of the first complete remission (CR1) was 7.1 months (range, 0.7-105.7 months). Philadelphia chromosome (Ph) and EM lesions at diagnosis were observed in 21 and 21 patients, respectively. Allo-SCT in CR1 was undergone in 12 patients. EM relapses occurred in 21 patients, and the sites of EM relapses were central nervous system (CNS) in 13, mediastinum in two, and bone in two. The median durations of CR1 were not significantly different between relapses with and without EM lesions (16.8 vs. 6.7 months, respectively; p = 0.295). In univariate analysis for risk factors of EM relapses, there was no significant difference in EM relapse rates between relapses after allo-SCT and chemotherapy (8.3% vs. 26.3%, respectively; p = 0.279), and in multivariate analysis, only EM lesion at diagnosis was identified as independent risk factor (odds ratio 4.21; p = 0.008). Of the 110 allo-SCT recipients included in the second part, the median age at diagnosis was 43 years (range, 16-66 years). Ph and EM lesions at diagnosis were observed in 43 and 21 patients, respectively. Disease status at the time of transplant was CR1 in 67, advanced CR in 17, and non-CR in 26. Stem cell sources were related, unrelated, and cord blood in 30, 50, and 25 patients, respectively, and almost all patients were conditioned with total body irradiation-containing myeloablative regimens. EM relapse after allo-SCT occurred in nine patients, and the 2-year CI of EM relapses was 6.5%. The sites of EM relapses after allo-SCT were CNS in three, lymph node in two, and skin in two. In univariate analysis for EM relapses after allo-SCT, the significantly higher CI of EM relapses after allo-SCT was observed in patients with EM lesion at diagnosis when comparing with those without EM lesion (28.6% vs. 1.1%, respectively; p = 0.279). Multivariate analysis extracted only EM lesion at diagnosis as an independent risk factor for EM relapses after allo-SCT (hazard ratio 24.09; p = 0.004). Conclusion: As a higher frequency of EM relapse after allo-SCT in ALL patients was not confirmed in this study, the hypothesis, more potent GVL effect in EM lesion than BM, was not able to apply to these patients. To determine whether this hypothesis is correct or not, further investigation in patients with other hematologic malignancy such as chronic myeloid leukemia is warranted. The vigilance is required regarding EM relapses in adult ALL patients with EM lesion at diagnosis both after chemotherapy and allo-SCT. Disclosures Handa: Ono: Research Funding.

scholarly journals Risk Factor Analysis for Infection after Medial Open Wedge High Tibial Osteotomy

2021 ◽  
Vol 10 (8) ◽  
pp. 1727
Author(s):  
Ta-Wei Liu ◽  
Chih-Hao Chiu ◽  
Alvin Chao-Yu Chen ◽  
Shih-Sheng Chang ◽  
Yi-Sheng Chan
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Multivariate Analysis ◽  
High Tibial Osteotomy ◽  
Univariate Analysis ◽  
Arthroscopic Surgery ◽  
Underlying Disease ◽  
Tibial Osteotomy ◽  
Open Wedge ◽  
Wedge High Tibial Osteotomy

Background: Medial open wedge high tibial osteotomy (MOWHTO) is a well-established treatment for osteoarthritis of the medial tibiofemoral compartment. Surgical site infection (SSI) after MOWHTO is a devastating complication that may require further surgery. In this study, we aimed to identify the risk factors for infection after MOWHTO over 1 to 4 years of follow-up. Methods: Fifty-nine patients who underwent MOWHTO combined with knee arthroscopic surgery were included in this prospective study. Artificial bone grafts were used in all cases. Possible risk factors, including sex, age, body mass index (BMI), underlying disease, hospitalization length, correction angle, and surgery time, were recorded. Both univariate and multivariate analysis were used. Results: A total of 59 patients who underwent 61 operations were included. Eleven patients (18.0%) were reported to have SSI. Univariate analysis showed that smoking and diabetes mellitus were positively associated with SSI. Multivariate analysis showed that smoking and age were positively associated with SSI. Three patients (4.9%) were reported to suffer from deep SSI, requiring surgical debridement, all of whom were male smokers. Conclusion: Smoking, diabetes mellitus, and old age were identified to be possible risk factors of SSI after MOWHTO. These findings are common risk factors of SSI after orthopedic surgery according to the literature. Patient selection should be performed cautiously, and postoperative prognosis for MOWHTO should be carefully explained to patients who smoke.

scholarly journals Prediction of Outcome for Transabdominal Cerclage in Women with Cervical Insufficiency

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Ji Eun Song ◽  
Keun Young Lee ◽  
Ga Hyun Son
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cohort Study ◽  
Pregnancy Outcomes ◽  
Retrospective Cohort ◽  
Multivariate Analyses ◽  
Univariate Analysis ◽  
Cervical Length ◽  
Cervical Insufficiency ◽  
Prediction Of Outcome

We investigated pregnancy outcome following transabdominal cerclage (TAC) in women with cervical insufficiency (CI) and explored parameters for predicting pregnancy outcomes following TAC. In this retrospective cohort study, we included 161 women with TAC. We considered demographic, obstetric, and gynecologic histories, pre- and postoperative cervical length (CL), and CL at 20–24 weeks as parameters for predicting outcomes following TAC. Univariate and multivariate analyses were used to identify risk factors for predicting delivery before 34 weeks after TAC. 182 pregnancies occurred after TAC, and 290 pregnancies prior to TAC were identified. The rate of delivery <34 weeks significantly decreased following TAC (5% versus 82%,P<0.001). Univariate analysis demonstrated that a short CL (<25 mm) at 20–24 weeks and adenomyosis were associated with delivery at <34 weeks’ gestation following TAC (P=0.015andP=0.005, resp.). However, multivariate analysis demonstrated that only a short CL (<25 mm) at 20–24 weeks was a significant predictor (P=0.005). TAC is an efficacious procedure that prolongs pregnancy in women with CI. A short CL at 20–24 weeks may predict the delivery at <34 weeks’ gestation following TAC.

Sign in / Sign up

Export Citation Format

Share Document