Therapeutic CSF Primed Donor Lymphocyte Infusion Using Cells Reserved at the Time of Transplantation for Patients with Relapsed Hematologic Malignancies after allo-PBSCT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5285-5285
Author(s):  
Sang Kyun Sohn ◽  
YoonYoung Cho ◽  
JongGwang Kim ◽  
YeeSoo Chae
Keyword(s):  
High Risk ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Donor Lymphocyte Infusion ◽  
Cd34 Cells ◽  
New Development ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Intent To Treat ◽  
Relapsed Disease

Abstract Background Reharvesting leukocytes from donors for a donor lymphocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. The effect of a growth factor-primed DLI is known to be comparable to that of nonprimed DLI for patients with relapsed disease. We reserved some portion of PBSCs harvested at the time of transplantation for the purpose of future DLI for relaping disease. Method In total, ninety nine patients (43 high risk, 46 standard disease) with hematologic malignancies who were treated by allo-PBSCT were allocated on an intent-to-treat basis. The dose of CD34+ cells with a range of 2–6*106/kg was transplanted, and additional PBSCs were cryopreserved. Result PBSC harvest for transplantation allowed to reserve extra cells in 35 (67.3%) high risk patients and in low risk 25 (55.6%) patients. Among 29 patients (29.9%) who relapsed after allogeneic PBSCT, 19 (65.5%) patients were treated with mainly cytarabine-based chemotherapy followed by cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLI was 1.43*108/kg and 4.75*106/kg, respectively. Six (24.9%) out of 19 relapsed patients exhibited a complete response after the primed DLI, and their 1-year survival rate was 36%. The new development or progression of graft-versus-host disease after the primed DLI was observed in 16 (82%) patients. Overall, the survival at 1 year after the primed DLI was 21%. Conclusion The induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the time of transplantation, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach seem to be more convenient for donors.

Prospective Evaluation Of Allo-HSCT From Haploidentical-Related Donors Compared With Matched Sibling Donors and Unrelated Donors For Patients With Hematological Malignancies: Results From An Open-Label Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3338-3338
Author(s):  
Yi Luo ◽  
Haowen Xiao ◽  
Xiaoyu Lai ◽  
Jimin Shi ◽  
Yamin Tan ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Prospective Trial ◽  
Hematologic Malignancies ◽  
Treatment Schedule ◽  
Hematopoietic Stem ◽  
High Risk Patients ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Matched Sibling

Abstract Introduction The order of alternative donor selection for hematopoietic stem cell transplantation (HSCT) for patients with hematologic malignancies has not been addressed. We performed the first prospective trial to compare the effect of HSCT from matched sibling donors (MSDs), unrelated donors (URDs) and haploidentical- related donors (HRDs) in a contemporary protocol. Methods From 2008 to 2012, 234 patients with hematologic malignancies were enrolled. The treatment schedule was as follows: if a fully MSD was available, patients were assigned treatment with MSD-HSCT. If an MSD was unavailable, a suitably matched URD was used as the alternative, where a suitable match involved matching more than 8 of 10 HLA-A, -B, -C, -DRB1and DQ allele loci ( ¡Ý 8/10) and at least 5 of 6 matching HLA-A, -B, and -DRB1 antigen loci. If only URDs with > 2 mismatching allele loci were available, patients were allowed treatment with HRD-HSCT. Results (1) Sixty-eight patients underwent MSD-HSCT, 98 patients underwent URD-HSCT, and 68 patients underwent HRD-HSCT (Table 1). (2) Grades II¨CIV and severe aGVHD were all significantly more frequent in patients undergoing HRD-HSCT compared with those undergoing MSD-HSCT (II¨CIV: 42.6% vs 19.1%, P = 0.0015; severe aGVHD: 17.65% vs 5.88%, P = 0.03). However, the incidences of II¨CIV and severe aGVHD were comparable in patients receiving transplants from HRDs to those from URDs (II¨CIV: 42.6% vs 40.8%, P = 0.89; severe aGVHD: 17.65% vs 13.27%, P = 0.48). The incidence of cGVHD was not significantly affected by donor types. (3) The 4-year incidence of relapse was not significantly affected by donor types according to all patients (24.2% in the MSD cohort, 22.8% in the URD cohort, 11.9% in the HRD cohort, P > 0.05). However, after controlling for high-risk patients, a superior graft-versus-leukemia (GVL) effect was observed in patients undergoing HRD-HSCT compared to MSD-HSCT or URD-HSCT. In high-risk patients receiving MSD, 36.8% experienced relapse, as did 33.6% in the URD cohort, but the incidence decreased to11.1% in the HRD cohort (MSD vs HRD, P = 0.015; URD vs HRD, P = 0 .028). (4) HRD-HSCT yielded comparable rates of 4-year overall survival (OS) and disease-free survival (DFS) to MSD-HSCT ( OS: 66.4% vs 79.5%, P = 0.071; DFS: 66.4% vs 78.2 %, P = 0.109) or URD-HSCT (OS: 66.4% vs 59%, P = 0.952; DFS: 66.4% vs 58.1%, P = 0.864) (Figure 1). Conclusion Our data provide convincing clinical evidence to support the use of HRDs, as well as URDs, can be selected as first-line alternative donors, especially for high-risk patients. Disclosures: No relevant conflicts of interest to declare.

Prospective Evaluation of Allogeneic Hematopoietic Stem-Cell Transplantation From Matched Related and Matched Unrelated Donors in Younger Adults With High-Risk Acute Myeloid Leukemia: German-Austrian Trial AMLHD98A

2010 ◽  
Vol 28 (30) ◽  
pp. 4642-4648 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Mack ◽  
Michael Stoppel ◽  
Franz Király ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Younger Adults ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Risk Patients ◽  
Unrelated Donors ◽  
Acute Myeloid

Purpose To assess the impact of allogeneic hematopoietic stem-cell transplantation (HSCT) from matched related donors (MRDs) and matched unrelated donors (MUDs) on outcome in high-risk patients with acute myeloid leukemia (AML) within a prospective multicenter treatment trial. Patients and Methods Between 1998 and 2004, 844 patients (median age, 48 years; range, 16 to 62 years) with AML were enrolled onto protocol AMLHD98A that included a risk-adapted treatment strategy. High risk was defined by the presence of unfavorable cytogenetics and/or by no response to induction therapy. Results Two hundred sixty-seven (32%) of 844 patients were assigned to the high-risk group. Of these 267 patients, 51 patients (19%) achieved complete remission but had adverse cytogenetics, and 216 patients (81%) had no response to induction therapy. Allogeneic HSCT was actually performed in 162 (61%) of 267 high-risk patients, after a median time of 147 days after diagnosis. Graft sources were as follows: MRD (n = 62), MUD (n = 89), haploidentical donor (n = 10), and cord blood (n = 1). The 5-year overall survival rates were 6.5% (95% CI, 3.1% to 13.6%) for patients (n = 105) not proceeding to HSCT and 25.1% (95% CI, 19.1% to 33.0%; from date of transplantation) for patients (n = 162) receiving HSCT. Multivariable analysis including allogeneic HSCT as a time-dependent covariable revealed that allogeneic HSCT significantly improved outcome; there was no difference in outcome between allogeneic HSCT from MRD and MUD. Conclusion Allogeneic HSCT in younger adults with high-risk AML has a significant beneficial impact on outcome, and allogeneic HSCT from MRD and MUD yields similar results.

scholarly journals Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 2139-2149 ◽  
Author(s):  
JH Antin ◽  
BE Bierer ◽  
BR Smith ◽  
J Ferrara ◽  
EC Guinan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
High Risk ◽  
Graft Versus Host Disease ◽  
Graft Failure ◽  
Hematologic Malignancies ◽  
Host Disease ◽  
Graft Versus Host ◽  
High Risk Patients ◽  
Risk Patients

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti- CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC- mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC- mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.

Blood tests to predict one- to two-year survival of patients with difficult cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16158-e16158
Author(s):  
Robert L. De Jager ◽  
Howard Bruckner ◽  
Fred Bassali ◽  
Elisheva Dusowitz ◽  
AJ Book ◽  
...  
Keyword(s):  
High Risk ◽  
Hospice Care ◽  
Intrahepatic Bile Duct ◽  
Stage Iv ◽  
Neutrophil Lymphocyte Ratio ◽  
Blood Tests ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Intent To Treat ◽  
Treat Analysis

e16158 Background: A sequence of drug combinations produces > 1 median (M) -strong 2-year (yr) survival (S) (Bruckner et al AACR 14 Antica Res (ACR) 16, 18 SIGO 19). Trials included high-risk patients (pts). Each initial series has 5-yr Ss, after pts were referred for hospice care. Prognostic ALAN blood tests (Ts) have been validated for stage IV (Adv) Cholangiocarcinoma (CCA) (Salati et al EuJCa18). Other Ts predict unexpected favorable (F) S of pts with gastric ca, PS 2-3. Bruckner et al JAMA, 82); but, there is little known about Ts for resistant (R) Ca. Methods: Planned Kaplan-Meier intent to treat analysis to find Ts that: expand eligibility (El) for therapy; identify biomarkers that predict therapy can prolong S and identify new hypotheses for therapy. El pts have:R to test drugs, Pancreatic (PC), Intrahepatic bile duct, CCA, Colon, CRC and new (N) APC. All series: -/+ high risk, -/+ aged, PS 0-2. El: Helsinki criteria- consent, recovered from severe (gr3) toxicity; able to reach office, -/+ help, and S > 6 wks. Inel: CNS involved, IV needed, F clinical factors predict 1 yr MST. Ts include A.L.A.N. scores, (AS) (Salati ibid) and other blood Ts (ACR ibid, Lavin et al CTR 82) Therapy GFLIO in mg/M2: gemcitabine 500, leucovorin 180, fluorouracil 1200, 24 hr infusion. Irinotecan 80 D2 Oxaliplatin 40. Then for progression (pg), add docetaxel 20-25, except CRC mitomycin C 4-6; next pg add cetuximab, except APC or KRAS-M, weekly, and next pg replace cetuximab with bevacizumab 10mg/kg ibid ACR 16. Results: At all ages, overall (O) S is > 1 yr for RCRC, and NAPC and sets with any 1 F or UnF T other than < 3.1 Albumin (Alb) or < 2.1 lymph/monocyte ratio (LMR) b For CCA, 17R/16N, OMS > 2 yrs 66% of pts and ≥ 2 yrs for all test sets except UnF, 26% of pts, MS 17 mos, with low Alb. For CRC: 50R OMS is 16.5 mos; 42% S 2 yrs, Fav Ts: MS > ̃ 2yrs, 39-82% of pts have FTs; Neutrophil Lymphocyte Ratio (NLR); < 3.1, 61% S 2 yrs, p < .02; Lymphs > 1.5, 53% S 2 yrs, p < .02; AS 0; 59% S 2 yrs, p < .06; Platelets < 300,000, 54% S 2 yrs, p < .06; Alb: ≥ 3.5, 48% S 2 yrs, p < .11. For N-APC: 53 pts, OS is 14.5 mos and > 12 mos in sets with any 1 UnF T other than Alb or LMR. FTs: MST 16.4-18 mos. 34-77% of pts have FTs; Alb ≥ 3.5, 34% S 2 yrs, p < 0.001; WBC < 10, 29% S 2 yrs, p < .06; AS 0-2, 35% S 2 yrs, p 2.7E-7. For R-PC: 53 pts, OS is 12 mos for 44% of pts, FTs: MST 13.6-17 mos, 21-70% of pts have FTs: Alb ≥ 3.5 30% S 2 yrs, p .0004; AS: 0, 41% S 2 yrs, p .0006; NLR < 3, 37% S 2 yrs, p < .02. GFLIO’s < 5% gr3 induction toxicity, is reversible, with no hospitalization, neutropenic fever or gr3 neuropathy. Conclusions: Robust Ts identify many difficult pts with median > 1 and testable prospective > 2 yr rates of S. Ts warrant development: validation with GFLIO and other therapy and other cancers; to improve Ts, models for eligibility and geriatric criteria; to identify false -/+ trials; and personalize trials to correct UnF Ts. FTs, with GFLIO, can change prognosis and practice for > 50% of pts now advised “against” any therapy due to a clinical estimate of “less than 6 -10 mos to live.” Clinical trial information: NCT01905150.

Defining the Role of Donor Lymphocyte Infusion in High-Risk Hematologic Malignancies

2021 ◽  
Vol 39 (5) ◽  
pp. 397-418
Author(s):  
Christoph Schmid ◽  
Jürgen Kuball ◽  
Gesine Bug
Keyword(s):  
High Risk ◽  
Hematologic Malignancies ◽  
Donor Lymphocyte Infusion

Oxycodone-induced neurotoxicity secondary, to concurrent voriconazole use in a patient with cancer

2017 ◽  
Vol 13 (3) ◽  
pp. 141 ◽  
Author(s):  
Lana Alghothani, MD ◽  
Jillian Gustin, MD
Keyword(s):  
Chronic Pain ◽  
High Risk ◽  
Adverse Effects ◽  
Advanced Disease ◽  
Hematologic Malignancies ◽  
Patients With Cancer ◽  
Concurrent Use ◽  
Underlying Malignancy ◽  
Risk Patients ◽  
Active Disease

Chronic pain is common in patients with underlying malignancy with prevalence of up to 70 percent in those with advanced disease. Opioids are often used for those with both active disease and chronic cancer-related pain. In high-risk patients with hematologic malignancies and pneumonia, the Infectious Diseases Society of America recommends empiric antifungal therapy, often with voriconazole or another similar azole agent. Thus, patients with cancer are commonly on medications, such as antifungals, that have the potential to interact with opioids, causing adverse effects. Our case demonstrates severe neurotoxicity due to the concurrent use of voriconazole and oxycodone.

Outcome and Prognostic Factors after Unrelated Donor Umbilical Cord Blood Transplantation in Adult Patients with Hematologic Malignancies Transplanted in Early Disease Stages.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2149-2149 ◽  
Author(s):  
Guillermo Sanz ◽  
Ignacio Lorenzo ◽  
Federico Moscardo ◽  
Dolores Planelles ◽  
Luis Larrea ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Early Disease ◽  
Blood Transplantation ◽  
Cd34 Cells ◽  
Grade Ii ◽  
Disease Stages

Abstract Stage of the disease at transplant is critical for outcome after unrelated donor umbilical cord blood transplantation (UD-UCBT). The results of UD-UCBT in adults transplanted early in the course of their disease are unclear. Thus, UD-UCBT remains as the last resort for most patients. The major aim of this report was to study the outcome of a series of adult patients with hematologic malignancies undergoing UD-UCBT early in the course of their disease in a single institution. From May 1997 to May 2004, 40 patients in early disease stages underwent UD-UCBT. All patients received thiotepa, busulfan (orally in 29, intravenously in 11), cyclophosphamide, and antithymocyte globulin (Lymphoglobulin in 24 and Thymoglobulin in 16) as conditioning, cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis, and filgrastim to fasten engraftment. Diagnosis were chronic myeloid leukemia in chronic phase in 14 cases, high-risk acute lymphoblastic leukemia in 14 (12 in CR1, 1 in CR2, and 1 in CR3), high-risk acute myeloblastic leukemia in 8 (7 in CR1 and 1 in CR2), and high-risk myelodysplastic syndrome in 4 (3 untreated and 1 in CR1). Median age was 27 years (range, 16–46). The degree of HLA match (HLA-A and -B by serology and -DRB1 by high-resolution DNA typing) was 6/6 in 2 (5%), 5/6 in 18 (45%), and 4/6 in 20 cases (50%). The median number of nucleated and CD34+ cells infused was 1.8 x 107/kg (range, 0.9–4) and 0.8 x 105/kg (range, 0.1–5.7) respectively. Median time to PMN above 0.5 x 109/L and to platelets above 20 x 109/L was 22 days (range, 13–44) and 69 days (range, 32–188), and the cumulative incidence of myeloid and platelet engraftment was 90% (95% CI, 81–99%) and 70% (95% CI, 57–86%), respectively. Time to myeloid engraftment showed a direct relationship with the number of CFU-GM and CD34 cells cryopreserved (P = .02 and .01 respectively) and infused (P = .0001 and .0004 respectively). Platelet engraftment was faster in patients receiving grafts with a higher number of CFU-GM (P = .005) and CD34+ cells (P = .04), in those receiving Thymoglobulin (P = .02) and in those not developing acute GVHD above grade II (P = .04). Eight patients (20%) developed acute GVHD above grade II, and 9 of 25 patients at risk had extensive chronic GVHD. Patients receiving Thymoglobulin had a lower risk of acute GVHD (P = .0003). With a median follow-up of 33 months (range, 3–87), the probability of disease-free survival (DFS) at 3 years was 48% (95% CI, 30–66%) and was related directly to age (P = .004) and inversely to the development of acute GVHD above grade II (P = .004). The probability of DFS at 3 years was 66 % for patients younger than 31 years and 54% for those not developing acute GVHD above grade II. Cell dose, degree of HLA mismatch, and diagnosis did not clearly influence DFS. These results compare to those obtained after matched unrelated donor bone marrow transplantation, and suggest that UD-UCBT is a reasonable first-line option for adults with hematologic malignancies requiring transplantation and lacking a HLA-matched sibling donor.

Haploidentical Allogeneic Hematopoietic Cell Transplantation in Adults Using Reduced Intensity Conditioning and CD3/CD19-Depleted Grafts: Interim Analysis of a Phase I/II Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1962-1962
Author(s):  
Birgit Federmann ◽  
Martin Bornhauser ◽  
Dietrich W. Beelen ◽  
Gernot Stuhler ◽  
Lambros Kordelas ◽  
...  
Keyword(s):  
Stem Cells ◽  
High Risk ◽  
Complete Remission ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Reduced Intensity Conditioning ◽  
Cd34 Cells ◽  
Risk Patients ◽  
Grade Ii ◽  
Reduced Intensity

Abstract Haploidentical hematopoietic cell transplantation (HHCT) after high dose conditioning with a megadose of CD34-selected stem cells has been complicated by regimen related toxicities, slow engraftment and delayed immune reconstitution leading to high treatment related mortality (TRM). A new regimen using reduced intensity conditioning (RIC) and immunomagnetic CD3/CD19 graft depletion may allow HHCT with lower toxicity and faster engraftment. CD3/CD19 depleted grafts not only contain CD34+ stem cells but also graft-facilitating cells, CD34- progenitors, dendritic and natural killer cells which may allow stable engraftment even without a megadose of CD34+ cells. A multicenter phase I/II study of HHCT using RIC with fludarabine (150–200 mg/m2), thiotepa (10 mg/kg), melphalan (120 mg/m2), OKT-3 (5 mg/day, day -5 to +14) and CD3/CD19 graft depletion has been initiated. No post grafting immunosuppression was applied if the graft contained &lt;5x104 CD3+ cells/kg. To date, 51 patients with a median age of 45 years (range, 19–65) have been enrolled in this study. Diagnosis were AML (n=34), ALL (n=7), NHL (n=6), MM (n=2), and CML (n=2). Patients were “high risk” because of relapsed or refractory disease (n=30), or relapse after preceding HCT (auto=7, allo=14). Stage at HCT was complete remission (n=25) and partial remission (n=26). The CD3/CD19 depleted haploidentical grafts contained a median of 7.1 x 106 (range, 3.4–18x106) CD34+cells/kg, 3.9 x104 (range, 0.6–44x104) CD3+T cells/kg and 2.8x107 (range, 0.02–37.3x107) CD56+cells/kg. The regimen was well tolerated with maximum acute toxicity being CTC-grade 1–2 mucositis. Five cases of reversible peripheral neuropathy and three cases of progressive multifocal leukencephalopathy (PML) occurred posttransplant in heavily pretreated patients. Engraftment was rapid with median time to &gt;500 granulocytes/μL of 12 days (range, 9–50) and to &gt;20000 platelets/μL of 11 days (range, 7–38). Full donor chimerism was reached after 2–4 weeks in all but four patients (median of 14 days (range, 7–215)). Four patients experienced rejection/non-engraftment, two were rescued by a second CD3/CD19 depleted graft from another haploidentical donor. Incidence of grade II-IV acute GVHD was 51% with grade II=16, III=6 and IV=4. So far there are six cases of limited chronic GVHD and one case of extensive chronic GVHD. TRM in the first 100 days was 11/51 (22%) and overall 20/51 (39%). Overall survival is 17/51 patients (33%) with deaths due to relapse (n=14), infection (n=15), PML (n=2), GVHD (n=2) and cardiac failure (n=1), with a median follow-up of alive patients of 397 days (range, 62–1180). This results in a Kaplan-Meier estimate 1-year survival of 37%. So far, we did not observe a statistical significant survival advantage for patient transplanted from a KIR-mismatched donor (28/51 patients). This regimen with low toxicity as well as fast and sustained engraftment is promising in high risk patients lacking a suitable donor. To investigate the treatment protocol earlier in course of disease a new study for high-risk patients with acute leukemia in first complete remission is in preparation.

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