Low Transplant Related Mortality Following Matched Unrelated Donor Allogeneic Transplantation in High Risk Patients Utilizing Low Dose Subcutaneous Campath.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5085-5085
Author(s):  
Scott R. Solomon ◽  
Karen Manion ◽  
Asad Bashey ◽  
Lawrence E. Morris ◽  
H. Kent Holland
Keyword(s):  
High Risk ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Median Number ◽  
Unrelated Donor ◽  
Actuarial Survival ◽  
High Risk Patients ◽  
Risk Patients ◽  
Related Mortality

Abstract The administration of alemtuzumab (Campath 1H) as part of the conditioning regimen prior to allogeneic stem cell transplantation (ASCT) results in a low incidence of acute and chronic GVHD. However, intravenous Campath administration is also associated with significant infusional toxicities and a higher risk of infectious complications post-transplant. We evaluated the role of low-dose subcutaneous Campath prior to unrelated donor ASCT in 13 patients deemed to be at high risk for mortality (age>40years, significant comorbidity, or prior autologous transplant). Median age of transplant recipients was 54 (37–61) years and three patients had a prior autograft. Diseases included secondary/poor risk AML-5, CML-1, MPS-2, relapsed HD-1, NHL-3, and CLL-1. The preparative regimen consisted of fludarabine and targeted oral busulfan (myeloid malignancies) or cytoxan±rituximab (lymphoid malignancies). Campath was administered subcutaneously from d-5 to d-3 at a total dose of 43mg. Low dose Campath was well tolerated with no untoward toxicity. Early mixed T cell chimerism generally occurred (median day +100 donor CD3 60% (8–100) and CD33 100% (67–100)), requiring door lymphocyte infusion (DLI) in 10 of 13 patients. Ten of 11 evaluable patients achieved complete donor chimerism at a median of 112 days (32–260), and no graft failures have occurred. Acute graft-versus-host disease (GVHD) occurred in 5/13 patients (38%) at median day +58 (23–152) (grade I[1] and II[4]). Chronic GVHD occurred in 6/12 evaluable patients (3 limited, 3 extensive) and no GVHD mortality has occurred. CMV reactivation occurred in 5 of 9 at-risk patients (55%) with a median day to reactivation of day +25 (9–38), median number of reactivations of 2 (1–4), but no CMV disease or mortality. After a median follow-up of 340 (84–631) days, eleven of thirteen patients survive for a one year actuarial survival of 83%. No patient has died from treatment-related mortality. Relapse occurred in 5/13 patients resulting in the death of two patients. Low dose subcutaneous campath administered during conditioning results in low TRM and promising survival in older high risk patients undergoing unrelated donor ASCT. Figure Figure

Low-Dose Decitabine Combined with Modified Bucy Is More Effective Conditioning Regimen for High-Risk Patients with Acute Myeloid Leukaemia/Myelodysplastic Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5750-5750
Author(s):  
Xiaowen Tang ◽  
Jing Cao ◽  
Xiaojing Shi ◽  
Ling Ge ◽  
Aining Sun ◽  
...  
Keyword(s):  
High Risk ◽  
Low Dose ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Advanced Stage ◽  
Free Survival ◽  
Risk Patients ◽  
Disease Free ◽  
Related Mortality

Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment options to hematologic malignancies. However, majority of patients with refractory or resistant AML/MDS can not achieve remission before transplantation. It is necessary to design a safe and effective conditioning regimen to reduce tumour burden, improve remission rates, decrease transplantation-related mortality, and improve disease-free survival (DFS) in patients with advanced acute myloid leukemia(AML) and myelodysplastic syndrom(MDS). One of the promising drugs of epigenetics is decitabine (DAC), which has a significant effect on a variety of hematologic malignancies including MDS and advanced AML. Furthermore, decitabine can not only up-modulate the tumor-associated antigen express on surface of leukemia cells to increase graft-versus-leukemia (GVL) effect but also can reduce the incidence of graft-versus-host disease (GVHD) by increase the number of regulatory T Cells (Tregs). Objective: To investigate the security and efficacy of conditioning regimen containing low-dose decitabine combined with modified BUCY regimen for advanced AML/MDS patients, explore the role of immunomodulatory activity post transplantation and compared this regimen with conventional modified BUCY regimen. Methods: Between January 2012 and March 2015, a total of 156 patients were enrolled in this retrospective study. In which, there were 46 patients who received a conditioning regimen of low-dose DAC and a modified BUCY regimen(DAC group) followed by allo-HSCT, and the second cohort consisted of 110 who only received a conventional modified BUCY regimen(Con group). Comparing the baseline of two groups, there were no significant difference except there were more advanced stage patients in DAC group(63% vs 32.7%,p=0.007). A modified BUCY conditioning regimen include semustine (250 mg/m2/d) for 1 d(-10d), cytarabine (2 g/m2 q12 h) for 2 d (-9 d to -8 d), busulfan (0.8 mg/kg/6 h) for 3 d (-7 d to -5 d), and cyclophosphamide (1.8 g/m2/d) for 2 d (-4 d to -3 d). Meanwhile, patients in the DAC group received the DAC treatment for 3 to 4 d with a total of 100 mg/m2 before modified BUCY regimen. Results: In DAC group, all patients engrafted successfully, including 29/46(63%) non-remission (NR) patients. However, there were seven patients presented graft failure in Con group. The transplantation-related mortality (TRM) rate was significantly lower in DAC group(0% vs 13.6%, p=0.019). The median time of neutrophil recovery was 12(10-21)d vs 12(10-23)d, and platelet recovery was 13(10-35)d vs 14(9-40)d, respectively in DAC and Con group, and there were no significant differences. With the median follow-up of 277.5(39-985)d and 221(3-1237)d in two groups, the cumulative relapse rate(RR) was 38.2% vs 36.8% (p=0.951). The incidence rate of aGVHD was lower in DAC group(26.7% vs 46.8%, p=0.034), while there were no diference in the incidence rate of cGVHD(68.4% vs 70.7%, p=0.598). Compared with Con group, the estimated 2-year overall survival (2yr-OS) rate and 2 year disease-free survival (2yr-DFS) rate were both higher in DAC group(2yr-OS:45.6% vs 75.3%, p=0.007, Fig 1; 2yr-DFS:39.1% vs 51.5%, p=0.076). Furtheremore, for patients in advanced stage before transplant, the estimated 2yr-OS was 37.2% vs 72.7%(p=0.009) and 2yr-DFS rate was 38.5% vs 49.8%(p=0.051), respectively. For AMLs, the estimated 2yr-OS rate in DAC and Con group was 75.0% vs 43.0%(p=0.034), and for advanced stage AMLs, the estimated 2yr-OS rate was 66.1% vs 29.7%( p=0.031). Regarding the early relapse rate(RR) of 6 months post transplant, DAC group were less than that of Con group(11.5% vs 35.3%, p=0.124). Conclusion: 1. Low-dose decitabine combined with modified BUCY is a safe and effective conditioning regimen for high-risk patients with AML/MDS with low toxicity and well tolerance. 2. 100% NR patients of DAC group achieved complete remission with full donor chimerism at d30. 3.Comparing with Con group, patients in DAC group had ralative lower incidence of aGVHD, TRM and RR but relative higher estimated 2-yr OS and DFS, especially for advanced stage patients. Disclosures No relevant conflicts of interest to declare.

Low Dose Subcutaneous Alemtuzumab and Preemptive Donor Lymphocyte Infusion without Withdrawal of Immunosuppression Results in Low Non-Relapse Mortality, Decreased Hospitalization, and Favorable Outcomes for High Risk Older Recipients of Unrelated Donor Allogeneic Transplants: A Prospective Phase II Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3016-3016
Author(s):  
Connie A. Sizemore ◽  
Asad Bashey ◽  
Karen Manion ◽  
H. Kent Holland ◽  
Lawrence E. Morris ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Donor Lymphocyte Infusion ◽  
Unrelated Donor ◽  
Preparative Regimen ◽  
Risk Patients ◽  
Prospective Phase ◽  
One Year

Abstract Abstract 3016FN2 Introduction Hematopoietic stem cell transplantation from unrelated donors (UD) is an effective treatment for hematologic malignancies, but has been associated with relatively high rates of high non-relapsed mortality (NRM) in older and less physically fit patients. The development of reduced-intensity preparative regimens has allowed the extension of this form of treatment to older high risk patients. We hypothesized that a reduced–intensity preparative regimen with pre-transplant low-dose Alemtuzumab would reduce early NRM from regimen-related toxicity and GVHD respectively following UD transplantation, and the early use of donor lymphocyte infusion (DLI) without withdrawal of immunosuppression would promote complete donor T cell chimerism (DC) and thus improve control of the patient's malignancy. We tested this hypothesis in a prospective phase II study. Methods Thirty six patients were treated. Patient characteristics: median age, 59 years (range, 42–68 years), PBSC (n=34) or bone marrow (n=2); 10/10 HLA locus matched (n=33) or 9/10 matched (n=3); diagnoses AML= 14, CML= 3, MDS=4, MPS=2, NHL=8 CLL=3, and HD=1; CIBMTR disease risk high [n=7], intermediate [n=15], low [n=14]. The conditioning regimen was fludarabine (40mg/m2/d days -6, -5, -4, -3) and busulfan (16mg/kg or i.v. equivalent) for myeloid malignancies or fludarabine (30mg/m2/d days -5, -4, -3), cyclophosphamide (750mg/m2/d days -5, -4, -3), ± rituximab (days -13, -6, +1, +8) for lymphoid malignancies. Low dose subcutaneous alemtuzumab was administered to all patients at a total dose of 43mg over 3 days (-11, -10, -9). Post-grafting immunosuppression consisted of tacrolimus and methotrexate (5mg/m2 on days 1, 3, and 6). Results Donor engraftment occurred in 35/36 (97%) patients with median times to neutrophil and platelet recovery of 16 days (10–20) and 16 days (0–42), respectively. One patient expired prior to recovery secondary to a sagittal sinus thrombosis. Early mixed T cell chimerism generally occurred (median day +100 donor CD3 52% (0–100) and CD33 100% (0–100)), requiring donor lymphocyte infusion (DLI) (starting dose 1 × 107 CD3 cells/kg) in 30 of 36 patients (83%, median day 65 [range 36–576]), while 12 received ≥ 2 DLI. Complete DC (defined as ≥ 95% donor cells in peripheral blood CD3+ and CD33+ cells) was achieved at a median of 180 days (range, 33–426 days). Ten patients never achieved completed DC. Maximal cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 42% (14% grade III-IV) and that of chronic GVHD was 59% (12% severe) in patients who survived more than 100 days. Cumulative probability of non-relapse mortality at day 100 and one year was 3% and 14%, respectively. Estimated overall survival at day 100 and one year was 97% and 71%, respectively. CMV reactivation by quantitative PCR was observed in 18 of 24 (75%) at-risk patients. However, no CMV-related disease or mortality was observed. No fungal infections or infectious deaths were seen before day 100. The median hospital length of stay from start of preparative regimen through Day +30 and +100 was 9 days (1–31) and 13 days (1–52), respectively. With a median follow-up of 2.4 years, the probabilities of 2-yr overall (OS) and disease-free survival (DFS) are 57% and 38%, respectively. Patients who achieved complete DC had better OS (log-rank p-value=0.024) (see figure) than patients who failed to achieve this status. In Cox analysis, development of chronic GVHD had a protective effect, associated with decreased relapse (HR 0.150, p=0.089) and improved DFS (HR 0.342, p=0.081). Conclusion Low dose alemtuzumab based conditioning and preemptive DLI in order to promote complete donor T cell chimerism, results in low treatment related mortality and favorable survival outcomes in an older patient population with high-risk malignancies undergoing unrelated donor transplantation. The use of pre-emptive DLI while maintaining immunosuppressive therapy appears to control the incidence of severe GVHD and is not associated with an increased risk on infections. Disclosures: No relevant conflicts of interest to declare.

The Use Of a Novel Nonmyeloablative Conditioning Regimen and Sirolimus For GvHD Prophylaxis To Transplant Patients With Chronic Granulomatous Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2157-2157
Author(s):  
Elizabeth M. Kang ◽  
Harry Malech ◽  
Dianne Hilligoss ◽  
Martha Marquesen ◽  
Corin Kelly ◽  
...  
Keyword(s):  
High Risk ◽  
Graft Failure ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Graft Versus Host ◽  
High Risk Patients ◽  
Gvhd Prophylaxis ◽  
High Risk Disease ◽  
Risk Patients ◽  
The One

Abstract Chronic Granulomatous Disease (CGD) results from a mutation in the NADPH oxidase complex. As a result, patients are prone to recurrent infections and an increased risk of autoimmune disorders such as colitis. Currently, the only available cure is hematopoietic stem cell transplantation using a related or unrelated donor. In 2002, the NIH published their results using a nonmyeloablative regimen and sibling matched donors. Although the results were overall promising, there was still significant GvHD in older patients and a number of graft rejections in the younger patients. Further accrual was limited due to donor unavailability. In 2007, after establishing an agreement with the National Marrow Donor Program, we were able to initiate a protocol for patients with primary immunodeficiencies using an HLA matched unrelated donor. The goal of this protocol was to achieve engraftment in patients with CGD, including high risk patients due to the presence of an ongoing infection or inflammation, without increasing the rate of graft versus host disease. We therefore devised a novel conditioning regimen of Busulfan, Campath, and TBI along with sirolimus as the sole GVHD prophylaxis. To date we have transplanted 21 evaluable patients. Results are summarized below:AgeInfectionInflammationaGvHDcGvHDadditional cells?A&Wcause of death32XX1Nrefused dialysis25XGrade 1Y21XXGrade 1Y19X (colostomy)Grade 4XNinfection, GvHD of skin17XX2NEvan's/TRALI/GvHD17XNpulmonary hemorrhage17XGrade 2Y12XlimitedXY7XY8XY8X (colostomy)Grade 1Y8XXY6XX3NGvHD after 3rd transplant5XY4XY4XXGrade 2Y17Y11Grade 1Y10Y10Y8Y 1. Received peripheral blood stem cells from same donor after receiving bone marrow 2. Received cells after additional conditioning in the setting of Evan’s syndrome 3. Received additional cells with initial graft failure. Went on to a second then third transplant with a different conditioning regimen and different donor. Overall survival was 76%; however all deaths occurred in high risk patients and 2 of the 5 were unrelated to the initial transplant. Further, all surviving patients transplanted with high risk disease (11 of the 16) continue to have stable engraftment and had complete resolution of their inflammation and/or infection. This includes a patient with P40phox deficiency whose primary manifestation of CGD was colitis as well as a patient with an invasive fungal infection requiring emergency laminectomy 3 weeks prior to transplant. We have had limited GvHD to date and this occurred primarily in the high risk patients (6 of the 7). The most severe GvHD occurred in a patient given additional cells due possible poor engraftment and persistent thrombocytopenia. In retrospect, this may have been a sign of GvHD and not graft failure; however the result was severe GvHD of the skin and ultimately death from sepsis. Further, the only chronic GvHD (transient, now resolved) was also in a patient given additional cells for concerns of possible graft failure. Subsequently, the protocol was modified to no longer give additional unmanipulated cells and no graft failures or any severe GvHD has occurred in any of the subsequent patients. In general, patients tolerated the transplant well, although we did see a higher than expected rate of engraftment syndrome, again in the high risk patients only (5 of 21). Many patients needed only 1 or 2 transfusions of either platelets or red blood cells and 3 did not require any transfusions at all. We also transplanted two patients with CGD/McLeod’s, banking autologous blood prior to the transplant, and only one patient required any blood (1 autologous unit). Three patients did require multiple infusions due to prolonged time to engraftment or slow platelet recovery including the one patient to receive bone marrow as their initial donor product. For the one patient with late graft failure, there was autologous recovery. Thus in this single centre study we have transplanted 21 patients to date including 16 of those considered high risk using a novel non-myeloablative transplant regimen and an unrelated donor. We have had significantly lower rates of GvHD (33%) of which <10% was greater than Grade 2 and only one patient with graft failure. Overall, the combination of Campath and Sirolimus, along with Busulfan and low dose radiation is well tolerated and has a low risk of graft versus host disease while still allowing engraftment in patients, even those with high risk disease. Disclosures: No relevant conflicts of interest to declare.

Feasibility of Prophylactic Pancreatojejunostomy in Possible High-Risk Patients for Prevention of Pancreatic Fistula during Enucleation or Limited Pancreatic Resection

2018 ◽  
Vol 84 (1) ◽  
pp. 149-153 ◽  
Author(s):  
Takao Ohtsuka ◽  
Yasuhisa Mori ◽  
Takaaki Fujimoto ◽  
Yoshihiro Miyasaka ◽  
Kohei Nakata ◽  
...  
Keyword(s):  
High Risk ◽  
Pancreatic Fistula ◽  
Pancreatic Resection ◽  
Medical Records ◽  
Operation Time ◽  
Postoperative Pancreatic Fistula ◽  
Postoperative Hospital Stay ◽  
High Risk Patients ◽  
Risk Patients ◽  
Related Mortality

The aim of this study was to assess the feasibility of prophylactic pancreatojejunostomy after enucleation or limited pancreatic resection regarding the risk of postoperative pancreatic fistula (PF). We retrospectively reviewed the medical records of 32 patients who underwent enucleation or limited pancreatic resection and compared the clinical parameters between patients with ( n = 10) and without ( n = 22) prophylactic pancreatojejunostomy. Prophylactic pancreatojejunostomy was performed in patients with a possible high risk ofPF. No operation-related mortality occurred. Operation time was significantly longer ( P < 0.01) and blood loss significantly greater ( P < 0.01) in patients with pancreatojejunostomy. Overall complications were more frequent ( P = 0.02) and postoperative hospital stay was significantly longer ( P = 0.02) in patients with pancreatojejunostomy. However, other assessed factors including the prevalence of postoperative PF did not differ between groups. In conclusion, prophylactic pancreatojejunostomy is feasible, and its efficacy in preventing PF after enucleation or limited pancreatic resection in high-risk patients will require further study.

Abstract 2471: Contemporary Results of Isolated Aortic Valve Replacement in High-Risk Patients in the Context of Emerging Percutaneous Approaches

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Pierre Voisine ◽  
Siamak Mohammadi ◽  
Josep Rodés-Cabau ◽  
Patrick Mathieu ◽  
Jean Perron ◽  
...  
Keyword(s):  
High Risk ◽  
Aortic Valve ◽  
Survival Benefit ◽  
Control Group ◽  
Perioperative Mortality ◽  
High Risk Patients ◽  
All Cause Mortality ◽  
Risk Patients ◽  
Related Mortality ◽  
Parsonnet Score

Percutaneous aortic valve replacement (AVR) is emerging as an alternative therapeutic approach for high-risk surgical patients, but criteria for patient selection are not clearly established. We sought to evaluate the perioperative and mid-term outcomes in a contemporary cohort of high-risk patients undergoing isolated AVR. Between 1997 and 2006, 855 consecutive patients underwent isolated AVR at our institution. High-risk patients (n=162, 19%) were defined by a preoperative Parsonnet score ≥ 30 or Euroscore ≥ 9. The remaining 693 patients (81%) composed the control group for comparison of perioperative mortality and mid-term freedom from all-cause and cardiac-related mortality. Mean follow up was 2.9±2.1 years. Perioperative mortality was 8.6% in the high-risk and 2.9% in the control group (p=0.0007), lower than that predicted by both scores (p<0.05). Freedom from all-cause mortality at 1 and 5 years were 94% and 82% for the control group and 87% and 65% for high-risk patients (p<0.0001). Freedom from cardiac-related mortality was also higher in the control (96% at 1 year, 91% at 5 years) than the high-risk (89% and 82%, p=0.0003) group. When considering patients who survived the 3-month perioperative period (537 in control, 114 in high-risk group), freedom from all-cause mortality was still higher in the former group at 1 and 5 years (99% vs 99% and 85% vs 75%, respectively, p=0.005), but freedom from cardiac-related mortality was not different (99% vs 100% and 94% vs 92%, respectively, p=0.3). By multivariate analysis, chronic renal failure, emergent procedures and reoperations were identified as independent predictors of mortality in high-risk patients. Contemporary perioperative mortality for isolated AVR in high-risk patients is lower than predicted by the Parsonnet score and Euroscore. Five-year survival in these patients is acceptable, and survivors of the operation experience the same cardiac-related survival benefit as those with standard perioperative risk. The perioperative survival benefit of percutaneous approaches for high-risk patients undergoing AVR remains to be demonstrated and, if present, should be weighed against mid-term outcome benefits of conventional surgical AVR.

Cervical Corpectomy With Ultra-low-dose rhBMP-2 in High-risk Patients: 5-year Outcomes

Orthopedics ◽  
2013 ◽  
Vol 36 (12) ◽  
pp. 931-935 ◽  
Author(s):  
Sina Pourtaheri ◽  
Arash Emami ◽  
Ki Hwang ◽  
Jesse Allert ◽  
Alex Brothers ◽  
...  
Keyword(s):  
High Risk ◽  
Low Dose ◽  
Cervical Corpectomy ◽  
High Risk Patients ◽  
Risk Patients

scholarly journals MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen

2019 ◽  
Vol 3 (1) ◽  
pp. 83-95 ◽  
Author(s):  
Haris Ali ◽  
Ibrahim Aldoss ◽  
Dongyun Yang ◽  
Sally Mokhtari ◽  
Samer Khaled ◽  
...  
Keyword(s):  
Molecular Markers ◽  
High Risk ◽  
Scoring System ◽  
Conditioning Regimen ◽  
International Prognostic Scoring System ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients ◽  
Transplantation Outcomes ◽  
Very High

Abstract Although allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF), data are limited on how molecular markers predict transplantation outcomes. We retrospectively evaluated transplantation outcomes of 110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen at our center and assessed the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System 70+ v2.0 (MIPSS70+ v2.0). With a median follow-up of 63.7 months, the 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. In mutational analysis, JAK2 V617F and ASXL1 mutations were the most common. By univariable analysis, higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS (hazard ratio [HR], 2.64; P = .032) and increased NRM (HR, 3.68; P = .004) after allo-HCT, but CALR, ASXL1, and IDH mutations did not have an impact on transplantation outcomes. Patient classification per MIPSS70 showed worse OS for high-risk (HR, 0.49; P = .039) compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients (HR, 0.291) and much lower OS when very-high-risk patients were compared with high-risk patients (HR, 5.05; P ≤ .001). In summary, we present one of the largest single-center experiences of Flu/Mel-based allo-HCT, demonstrating that revised cytogenetic changes and MIPSS70+ v2.0 score predict transplantation outcomes, and thus can better inform physicians and patients in making decisions about allo-HCT.

Low‐dose rectal diclofenac does not prevent post‐ERCP pancreatitis in low‐ or high‐risk patients

2019 ◽  
Vol 35 (7) ◽  
pp. 1247-1253 ◽  
Author(s):  
Takao Katoh ◽  
Kousaku Kawashima ◽  
Nobuhiko Fukuba ◽  
Shigeto Masuda ◽  
Hiroko Kobatake ◽  
...  
Keyword(s):  
High Risk ◽  
Low Dose ◽  
High Risk Patients ◽  
Risk Patients
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