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  • 1
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 1140-1140
    Abstract: FLIPI is emerging as an important prognostic factor in patients (pts) with FL. In order to determine its significance in FL pts undergoing AUTO, we examined the outcome of 75 consecutive pts transplanted at the MD Anderson Cancer Center between 02/94 and 04/08. Pts were eligible if they had relapsed chemosensitive disease, and had no HLAidentical sibling donor. Twenty-nine pts were transplanted without rituximab (AUTO-R), and 46 pts received high-dose rituximab (AUTO+R) during stem cell mobilization and on days +1 and + 8 after transplantation as previously described (Khouri, JCO, 2005). Median age (range) at AUTO was 54 (33–76) and 49 (35–63) for the AUTO+R and AUTO-R groups respectively (P =0.002). FLIPI was determined at the time of transplantation; more patients had intermediate-high risk in AUTO+R than in AUTO-R (58% vs 27.5%, respectively, P = 0.011). Other patients characteristics were balanced for gender, time from diagnosis, histology subtypes (grades 1,2, 3a, and 3b), disease stage, LDH, bulk, B-symptoms, B-2microglobulin, bone marrow involvement, number of prior chemotherapy regimens received, remission status (CR vs PR), functional imaging, and co-morbidity score. Median follow-up (range) in months was 20 (1–88) for AUTO+R and 70 (4–167) for AUTO-R. Progression-free survival (PFS) was significantly different between AUTO+R and AUTO-R (P = 0.004), with estimated three-year PFS of 48% for AUTO-R and 79% for AUTO+R. Using Cox proportional hazards regression models, the # of prior chemotherapy regimens received ( & lt;3 vs & gt;/=3) (P = 0.015) was the only factor associated with PFS in the AUTO+R group, whereas both age (P=0.010), and risk based on FLIPI (P=0.019) were independently associated with PFS in the AUTO-R group. Pts with low-risk vs. intermediate/high-risk had three-year PFS of 62% and 13%, respectively, in the AUTO-R group, whereas in the AUTO+R group, three-year PFS was 90% and 76% in the low-risk and intermediate/high-risk pts, respectively (Figure). Conclusions: These results suggest that the addition of R to the mobilization and conditioning improves the outcome in pts with relapsed chemosensitive FL treated by AUTO. The number of prior chemotherapy regimens received rather than FLIPI score is the most important determinant of outcome in this setting. Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 2
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3394-3394
    Abstract: Abstract 3394 Poster Board III-282 CB transplantation (CBT) is often complicated by delayed or failed engraftment. We conducted a study of ex vivo co-culture of CB mononuclear cells with either third party family member ≥ 2/6 HLA matched marrow derived MSCs (N=8) or off-the-shelf mesenchymal progenitor cells (MPCs) from Angioblast Systems Ltd. (N=9). MSCs provide a microenvironment for the generation of complex molecular cues that direct proliferation and regulate the differentiation and maturation of hematopoietic progeny. Patients had two CB units matched in at least 4/6 HLA antigens, with a minimum of 1×107 TNC/Kg per unit. Methods: Diagnoses were AML/MDS (N=10), ALL (N=3), NHL (n=1), MM (n=1), and CLL (N=2). Five patients (29%) were in CR (CR1, n=1) and 12 (71%) had active disease at CBT. Preparative regimen: myeloablative fludarabine, melphalan, thiotepa and ATG (n=17), with rituximab in the 3 ALL pts. GVHD prophylaxis: tacrolimus and MMF. Median weight was 79.7 Kg (range, 15-102) and median age was 36 years (2-55 years). Donor-recipient HLA matching was 5 of 6 in 29% of the cases and 4 of 6 in 71%. Ex-vivo EXP: 100 ml of marrow was aspirated from the family donor and MSCs generated in ten T175 flasks, which took ∼21 days (n=8) or one vial of Angioblast MPCs was thawed and expanded to confluence in 10 flasks within 4 days (n=9). The CB unit with the lowest TNC dose was then thawed, divided into 10 fractions, and each placed into 1 flask containing the confluent layers of MSCs/MPCs in expansion media with SCF, FLT3, G-CSF and TPO. After 7 days at 37°C, the non-adherent cells were removed from each flask, placed into each of ten one-liter Teflon-coated culture bags (American Fluoroseal) and cultured for an additional 7 days (14 days total), while 50 ml of media/growth factors was added to the flasks to culture the remaining adherent layer during that time period. On day 14 the cells from the bags and the flasks were combined, washed and infused along with a second unmanipulated CB unit. Results: The median number of infused total nucleated cell (TNC) and CD34+ cells per kg in unmanipulated CB was 2.3 × 107 (range, 1.9-8.2) and 1.6 × 105 (range, 0.3-1.26). There were no toxicities attributable to the EXP cells. The median TNC fold-EXP for recipients of family-MSCs was 11.7 (0.7-28) and for Angioblast-MPCs was 15.5 (3.1-22.5); Fold-EXP of CD34+ cells was 11.7 (1.7-50.1) for family-MSCs and 46.6 (3.85-71.9) for Angioblast-MPCs. The median number of infused TNC and CD34+ cells per kg after EXP for all pts was 5.8 × 107 (range, 0.1-1.43) and 6.05 × 105 (range, 0.18-30). Median time to neutrophil and platelet engraftment was 15 days (9-25 days) and 37.5 days (13-56). Sixteen (94%) and 14 (82%) of all patients engrafted neutrophils and platelets, respectively. One patient died before engraftment. All evaluable patients became complete donor(s) chimeras. One CB unit dominated in all patients; on transplant day +21, EXP unit contributed with a mean of 10% of T cell and 24% of myeloid chimerism; on day +40, corresponding proportions were 2% and 4%, and on day +70, 0% and 3%, respectively. Acute grade II-IV and III-IV GVHD rate was 38% and 12%, while 50% of at-risk patients developed chronic GVHD. Ten patients (59%) are alive (3-14 months after CBT), while 7 patients have died due to infections (n=4), relapse (n=2) and GVHD (n=1). Actuarial 6 and 12 month survival is 70% and 50%, respectively. Conclusion: The decreased logistical demands and expansion results demonstrate that off-the-shelf Angioblast-MPCs are the preferred stroma for this CB EXP procedure. MSC/MPC-CB EXP is feasible and may provide rapid engraftment of neutrophils and platelets. Platelet engraftment occurred in a high proportion of patients (80%) in this cohort of high-risk patients with a median weight of 80 Kg. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 3
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 3051-3051
    Abstract: It is unclear how related donor transplants in which the donor-recipient pair is mismatched in one locus (1AgMM) compare to transplants performed using a fully matched unrelated donor (MUD), matching at HLA-A, B, C, DRB1 and DQB1. Here, we performed such a comparison. Methods: We studied 83 consecutive patients (pts) with acute leukemias and myeloproliferative/myelodysplasia syndromes receiving grafts considered to be “1-antigen mismatched related” (1AgMM) and compared their outcomes to that of 134 MUD HSCT performed from 1992 to 2006. Among 83 1AgMM transplants, 40 had prospectively or retrospectively performed high-resolution HLA typing (Hires), of which 6 pts were 8/10 matched, and 43 had only low resolution (Lowres) typing. 8/10 Hires pts were excluded from this analysis. All MUD donor-recipient pairs were typed by Hires. Median age, gender, cytogenetic risk, disease status at transplant and stem cell source were similar. Diagnosis were ALL in 5% of the Hires group, 28% of the Lowres and 0 in the MUD group; AML/MDS cases were 76%, 60% and 87%, respectively; and CML cases were 19%, 12% and 13%, respectively(p 〈 0.001). Preparative regimens were of reduced intensity for 22% of Hires, 21% of Lowres patients and 40% of MUD patients (p=0.02). High-resolution typing was performed for HLA-A, B, DRB1, DQB1 and DPB1, and SBT/SSOP for HLA-C. Cumulative incidence of NRM, acute and chronic GVHD was estimated accounting for death in the absence of event as a competing risk. The Cox’s proportional hazards model was used to compare outcomes beteween groups. Results: With a median follow-up of 15 mo for MUD pts, 27 mo for Hires patients and 33 mo for Lowres pts, OS at 18 mo is 52%, 46% and 22% (p= 0.002 for the comparison of MUD vs Lowres; P=NS for the comparison of MUD vs Hires); NRM is 23%, 26% and 54%(p=0.001 for the comparison of MUD vs Lowres; P=NS for the comparison of MUD vs Hires). Primary graft failure occurred in 1% of MUD, 5% of MOL and 12% of SER (p=0.003). Cumulative incidence of grade II-IV aGVHD is 34% for MUD pts, 48% for Hires and 49% for Lowres(p= 0.07); cGVHD: 34%, 40% and 54%(p=0.01 for the comparison of MUD vs Lowres). We divided the Hires related group according to presence of Class I or Class II mismatches, and compared their outcomes to the MUD group (Table). 23 pts had Class I and 11 pts had Class II mismatches; median follow-up is 26 and 62 mo, respectively. Distribution of gender, diagnosis, cytogenetic risk, dis. status at transplant, ablative/RIC regimens and stem cell source was similar between the 2 groups. Pts with class I mismatches had the worse survival. Conclusion: Cumulative incidence of grade II-IV aGVHD and cGVHD, non-relapse mortality and overall survival of 1AgMM (allele level typing) patients was similar to that observed in a cohort of recipients of molecularly matched, HLA 10/10 MUD transplants. OS at 18 mo HR (95%CI) P C. Incid. gd II-IV aGVHD HR (95% CI) P C. Incid. chronic GVHD HR (95% CI) P C. Incid= cumulative incidence MUD n=134 52% Reference 34% Reference 34% Reference Class I n=23 34% 1.8 (1–3.1) P=0.05 40% 1.3 (0.6–2.9) P=0.4 35% 1.1 (0.5–2.5) P=0.7 Class II n=11 73% 0.6 (0.2–1.9) P=0.4 64% 2.8 (1.3–6.3) P=0.01 48% 2.3 (0.9–5.7) P=0.08
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 4
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1989-1989
    Abstract: Background: Impact of obesity on transplant outcome is unknown. We hypothesized that obesity increases allogeneic transplant related morbidity/mortality. We therefore performed a case control study of obese patients with AML and MDS undergoing allogeneic transplant (AlloSCT) at our institution. Patients and Methods: Sixty one patients with AML or MDS and a Body Mass Index (BMI) greater than 35 were transplanted from 1987 and 2006. 61 control patients were identified with BMI less than 30. The patients had similar characteristics. Controls were matched for age (within 5 years), disease status (relapse or remission), donor type (sib or MUD) and conditioning regimen. Results: The median weight of obese patients was 109.5 Kg (range 78–151.3 Kg). Obese and controls had similar distribution of age (median age 47 years and 46 years respectively). Likewise gender, disease status, and cytogenetic risk groups were similar in the two groups. The majority (62%) of patients in both groups had IV Busulfan based conditioning therapy, while 11% had a TBI based regimen and 26% in both groups had reduced intensity conditioning with Fludarabine and Melphalan. Donor was a matched sib in 65% of cases and 66% of controls. The median time between transplant day and discharge was 23 days (range 14–98days) in both groups. Only significant difference between the two groups was the presence of comorbidites in obese patients. 75% of cases had a comorbidty score of 3 or more compared to 38% of controls (p & lt;0.001) as defined by HCT index. Outcomes were similar in both groups. Two year non relapse mortality was 27% (95% CI: 18%-42%) in obese patients and 27% (95% CI: 17%- 41%) in control patients. Grade 3–4 toxicities occurred in 55% of cases compared to 42% of controls (p=0.2). Three-year disease free survival was 44% (95% CI: 31%- 57%) and 42% (95% CI: 29%- 55%) respectively in cases and controls. Median overall survival was 18 months for obese patients and 26 months for controls; 3-year overall survival was not significantly different in the two groups: 45% (95% CI: 31%- 58%) and 45% (95% CI: 31%- 58%) respectively for cases and controls. Conclusion: Despite the higher prevalence of comorbidities in obese patients, obesity did not impair outcome in patients with AML/MDS undergoing AlloSCT. Hence, obesity should not be considered a contraindication to AlloSCT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 5
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2977-2977
    Abstract: Introduction: Umbilical CBT from mismatched donors can restore hematopoiesis both in children and adults with acceptable rates of severe acute (aGVHD) and chronic GVHD (cGVHD). Acute and chronic GVHD, including risk factors, clinical manifestations and its specific impact on outcomes has not been systematically evaluated in this particular patient population. Objective: To analyze the manifestations of GVHD in CBT, with emphasis on risk factors and impact on overall survival. Methods: Prospective evaluation of aGVHD and cGVHD in 138 adult and pediatric patients undergoing single or double CBT for hematological disorders and solid tumors from 3/96 and 6/07. cord blood units were selected on the basis of a maximum of 2 MM (HLA-A, B, DRB1) and the minimum of 1x107TNC/Kg. Risk factors for aGVHD after CBT were assessed using the Cox proportional hazards method. The estimates of aGVHD and cGVHD were performed accounting for competing risks such as death and engraftment using the cumulative incidence (CI) method. Results: A total of 138 adult (n=78) and pediatric (n=60) CBT were performed in the time period. Median age was 21 (1-64), 58 females and 80 males. The majority received a transplant for hematological malignancies (n= 132), mostly MDS/AML and ALL (n= 98, 71%). The remainder had AA (n= 3) and one a solid tumor (n=1). Seventy-seven patients (56%) were in remission of their disease at the time of transplant. Most patients received a myeloablative regimen (n= 125, 91%), and single cord grafts (n= 81, 59%). Of 100 CBT where HLA typing is available, 39%, 45 and 9% have 1, 2 and 3 mismatched loci respectively. Twenty-four patients (17%) did not engraft. At 3 months post transplant, the CI of grade II-IV aGVHD was 36% (adult 38%, pediatric 34%, p= 0.9), and that of grade III-IV was 12% (adult 14%, pediatric 10%, p= 0.9). Skin was the organ most often involved (84%, adult 71%, pediatric 100%, p= 0.017). In adults skin was the only organ involved in 80% of patients with skin GVHD. Lower GI, upper GI and liver involvement were observed in 24, 18, and 21% of patients respectively, without significant difference between adults and children. The total nucleated cell count (TNC) of the graft was the strongest predictor of aGVHD. In children, active disease at the time of transplant was also significantly associated with higher incidence aGVHD. Other factors analyzed, including number and type of mismatched HLA loci were not significant risk factors for aGVHD. CI of cGVHD was 20%, and significantly lower in children compared to adults (8 vs 31%, p= 0.002). Nonrelapse mortality (NRM) at 2 years was 30%, and significantly lower in children (18 vs 41%, p= 0.007). Only 7/43 (16%) deaths were attributed to aGVHD or cGVHD. Conclusions: CBT can be performed in children and adults with acceptable rates of GVHD, even in the presence of multiple HLA mismatched loci. Most cases of acute GVHD involved the skin, often as the only organ. Chronic GVHD and NRM are significantly higher in adults. GVHD accounts for a relatively small proportion of nonrelapse deaths.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 6
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 16, No. 5 ( 2010-05), p. 686-694
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
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    detail.hit.zdb_id: 2057605-5
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  • 7
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 17, No. 10 ( 2011-10), p. 1490-1496
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
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  • 8
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 5112-5112
    Abstract: Background: (AL) Amyloidosis is a rare and potentially fatal disease that involves deposition of light chain protein by a clonal plasma cell population. Treatment with high dose melphalan and autologous stem cell transplant (ASCT) can improve survival and reverse organ damage, but this treatment is associated with toxicity and mortality. We reviewed the outcome of patients with amyloidosis, who received hematopoietic stem cell transplant (HSCT) at our institution. Patients and Methods: The retrospective study analyzed 32 patients with AL Amyloidosis who underwent transplant between 1997–2006. There were 17 men and 15 women, with a medium age of 53 years (range 35–73 years). All patients had diagnostic criteria for multiple myeloma (MM) and had biopsy confirmed amyloidosis of at least one organ site. Six patients had at least 1 organ involved with AL amyloidosis (3 bone marrows, 2 subcutaneous and 1 kidney), 20 patients had 2 organs involved, while 6 patients had 3 or more organs affected. All received a median of 3 cycles of chemotherapy (range 0–13) before transplant. Twenty-eight patients underwent autologous transplant, while 4 had an allogeneic transplants (2 syngeneic and 2 siblings). The preparative regimens received in 28 patients were high dose melphalan (26 autologous and 2 syngeneic), 2 patients received Busulfan and Melphalan, 2 allogeneic transplant Fludarabine and Melphalan. Results: The median Charlson Comorbidities Index (CCI) was 3 (range 0–8). The median number of CD34+ cells infused was 4.85 x 106 cells/kg (range 1.43–7.82 cells/kg). The median time to neutrophil and platelet engraftment were 11 (range 2–21days) and 14 days (range2–41), respectively. 56% of patients developed moderate to severe gastrointestinal effects. Four patients underwent allogeneic transplant and 1 had acute and chronic graft vs host disease (GVHD). Twenty-one patients (65%) achieved a partial hematological remission (PR), and 5 patients (15%) achieved complete hematological remission (CR), with a total response hematological rate of 80%. The 100 day NRM was 3.2%. The median overall survival was (OS) 41 months (range 1–108), 7 patients died (4 relapsed and 3 infections) all 7 patients had CCI greater or equal to 4. Conclusion: Selected patients with MM and amyloidosis can benefit from high dose therapy with stem cell support including allogeneic transplantation. The high mortality seen in patients with CCI 〉 4 suggests that this index could be useful in selecting patients for high dose chemotherapy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 9
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 48-48
    Abstract: The influence of chronic HC on the outcome of patients undergoing alloSCT is not clearly defined. We hypothesized that HC is associated with increased risk of non-relapse mortality (NRM) after alloSCT. We performed a retrospective matched-control study of the outcomes of 31 patients (table 1) with serological evidence of HC at the time of alloSCT performed between 1998 and 2007. Control patients (N=31) had negative serology for HC and were matched on age, diagnosis, disease stage, type of conditioning regimen and donor type (referred to as matched controls). To confirm the validity of the matching procedure we extended the comparison to the 1800 seronegative patients (all controls) transplanted for the same diagnoses during the same period of time in our institution. Multivariate analysis took into account all variables used in our matching algorithm. All HC patients had ALT levels less than 3 times the upper limit of normal and normal bilirubin levels at alloSCT. There were no significant differences in these parameters compared to control patients. Median follow-up was 34 (range 3–53), 27 (4–74) and 29 months (1–108), respectively for HC, matched and all controls. Overall survival post-alloSCT was significantly inferior in the HC group, with a median OS of 3 versus 18 and 20 months in the control groups. The cumulative rate of disease progression and acute or chronic GVHD was comparable, but NRM was significantly increased in the HC group (table 2). Results were similar regardless of the control group used, which validated our matching procedure. In conclusion, serological evidence of HC virus infection at the time of alloSCT, even with normal or minimally abnormal liver tests, is associated with worse survival in the context of alloSCT, due to an increased rate of non-relapse deaths. Table 1: Patient characteristics Characteristic HC (N=31) All controls (N=1800) P Matched controls (N=31) patient characteristics are identical to the HC group Median age (range) 49 (26–72) 47 (3–75) 0.2 Status at transplant: 0.2 - High risk (%) 19 (61) 905 (50) - Low risk (%) 12 (39) 895 (50) Donor type: 0.2 - Sibling (%) 21 (68) 1026 (57) - Unrelated (%) 10 (32) 760 (42) Preparative regimen: 0.02 - Reduced intensity (%) 21 (68) 754 (42) - Myeloablative (%) 10 (32) 1046 (58) Diagnosis: 0.7 - AML/MDS (%) 15 (48) 740 (41) - CML/MPD (%) 6 (19) 274 (15) - Lymphoma (%) 7 (22) 514 (29) - Myeloma (%) 2 (6) 87 (5) - ALL (%) 1 (3) 185 (10) Table 2: Patients with HC have worse OS and NRM than controls Matched analysis Multivariate analysis Outcome HC (N=31) vs. matched controls (N=31), % HR (95% CI) P HC (N=31) vs. all controls (N=1800), % HR (95% CI) P HC: hepatitis C, OS: Overall survival, NRM: Non-relapse mortality OS: 3 mo 58 vs. 87 3.6 (1.2–11.0) 0.03 58 vs. 87 3.9 (2.2–6.8) 〈 0.001 1 yr 29 vs. 56 2.4 (1.2–4.9) 0.01 29 vs. 56 3.1 (1.9–5.6) 〈 0.001 NRM: 3 mo 29 vs. 13 2.5 (0.8–8.1) 0.1 29 vs. 10 3.6 (1.8–7.1) 〈 0.001 1 yr 43 vs. 24 2.9 (1.1–7.7) 0.03 43 vs. 23 3.3 (1.9–5.6) 〈 0.01
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 10
    In: Cancer, Wiley, Vol. 115, No. 9 ( 2009-05-01), p. 1899-1905
    Type of Medium: Online Resource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2009
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