scholarly journals Transplantation of CD34+ enriched allografts in children with nonmalignant diseases: does graft manipulation necessarily result in high incidence of graft failure?

2003 ◽  
Vol 33 (1) ◽  
pp. 125-126 ◽  
Author(s):  
P Lang ◽  
R Handgretinger ◽  
J Greil ◽  
P Bader ◽  
M Schumm ◽  
...  
Keyword(s):  
Graft Failure ◽  
High Incidence

Donor-Type Aplasia After Bone Marrow Transplantation in Children with Aplastic Anemia: A Nationwide Retrospective Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 959-959 ◽  
Author(s):  
Nao Yoshida ◽  
Hiroshi Yagasaki ◽  
Hiromasa Yabe ◽  
Akira Kikuchi ◽  
Ryoji Kobayashi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Graft Failure ◽  
Dose Group ◽  
Independent Risk Factor ◽  
Conditioning Regimen ◽  
Japanese Children ◽  
Full Dose ◽  
High Incidence ◽  
Half Dose ◽  
Donor Type

Abstract Abstract 959 Survival after bone marrow transplantation (BMT) in children with aplastic anemia (AA) has improved markedly over the last 3 decades. However, we have experienced a certain number of patients who presented with bone marrow aplasia with full donor chimerism after BMT (donor-type aplasia), especially in the recent years. Since the 2000s, fludarabine (FLU)-based conditioning regimen has been often used for Japanese children with AA. The present study therefore evaluated whether patient and transplantation characteristics (especially the FLU regimen) could associate with donor-type aplasia in a large population of children with AA. To identify the risk factors for donor-type aplasia, we reviewed the clinical data of 660 patients (< 20 years) with AA who received BMT from 1980 to 2010 and whose records were available in the Japan Society for Hematopoietic Cell Transplantation Registry. The influence of potential risk factors on donor-type aplasia was assessed according to patient and transplantation characteristics, including the conditioning regimen. The median age at transplantation was 11 years, and 238 patients received immunosuppressive therapy (IST) before BMT. The median interval between diagnosis and BMT was 9 months. Regarding transplantation, 419 patients received BMT from related donors, whereas 241 received BMT from unrelated donors. Totally, 220 patients received a regimen that included FLU. Primary graft failure was observed in 25 patients. Of the 635 patients who achieved primary engraftment, 46 developed secondary graft failure or relapse: 11 were of the recipient-type and 35 were of the donor-type. The cumulative incidence of donor-type aplasia was 5.7%, and the 10-year overall survival of patients who presented with donor-type aplasia was 87%. Notably, the incidence of donor-type aplasia was significantly higher in FLU regimen group than in non-FLU regimen group (11.6% vs. 2.7%; P < 0.0001), and multivariate analysis confirmed that the FLU regimen was an independent risk factor for donor-type aplasia. Low infused cells (≤ 3×108/kg) (P = 0.008) and IST before BMT (P = 0.04) were also associated with a high incidence of donor-type aplasia. Age at BMT, gender, etiology, severity, interval between diagnosis and BMT, transfusion times, donor type (related or unrelated), human leukocyte antigen disparity, acute or chronic graft versus host disease (GVHD), GVHD prophylaxis, and viral reactivation or infection did not influence the incidence of donor-type aplasia in multivariate analysis. When FLU was introduced in the regimen for Japanese children with AA, the dose of cyclophosphamide (CY) was reduced by half, to reduce the toxicity; the conventional dose of CY was 200 mg/kg before the introduction of FLU. Therefore, we investigated the impact of the dose reduction of CY in the FLU regimen group. In patients receiving the FLU regimen, the incidence of donor-type aplasia in the CY half-dose group (n = 175) was 14%, whereas donor-type aplasia was not observed in the CY full-dose group (n = 35) (P = 0.04). In contrast, the addition of antithymocyte globulin or irradiation did not influence the incidence of donor-type aplasia in the FLU regimen group. Of note, the incidence of heart failure as a result of CY administration was higher in the CY full-dose group (5.7%) than in the CY half-dose group (0.6%), although this difference was not statistically significant. In conclusion, the FLU regimen was identified as an independent risk factor for donor-type aplasia in children with AA, which could possibly be ascribed to the CY dose reduction. However, the high incidence of heart failure associated with the regimen including a full dose of CY is an important issue that needs to be resolved. To develop optimal treatment, the conditioning regimen for children with AA needs to be reconsidered. Disclosures: No relevant conflicts of interest to declare.

Optimal Outcomes after Second Hematopoietic Stem Cell Transplantation in Patients with Thalassemia Recurrence Following Graft Failure/Rejection of the First Graft

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2289-2289
Author(s):  
Javid Gaziev ◽  
Katia Paciaroni ◽  
Gioia De Angelis ◽  
Antonella Isgro ◽  
Marco Marziali ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Total Dose ◽  
Graft Failure ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Treatment Protocol ◽  
Hematopoietic Stem ◽  
Second Transplantation ◽  
High Incidence

Abstract Introduction. Graft failure/rejection (GF/R) is a significant complication following HCT in non- malignant diseases. The risk of GF/R in patients with thalassemia is particularly high as a consequence of alloimmunization related to transfusion exposures and hyperproliferative marrow. Although the GF/R rate after myeloablative HLA-matched sibling transplants for thalassemia has been reduced, its incidence still remains high following alternative donor transplantation. Typically, GF/R after HCT for thalassemia is accompanied by autologous hematopoietic recovery, but occasionally patients develop GF with prolonged marrow aplasia. Given great variability in conditioning regimens and outcomes after second HCT for GF/R, it is important to develop a uniform treatment approach to patients receiving second transplantation for GF/R with autologous recovery. Methods. We report on 21 consecutive patients with median age of 9 years (range, 4-24 years) with thalassemia who underwent a second HCT for GF/R with autologous recovery. Ten patients had primary and 11 patients secondary GF/R following the first BMT. Median time to second transplant was 41 months (range, 8- 204). Treatment protocol consisted of preconditioning cytoreduction/immunosuppression with hydroxyurea (30 mg/kg/day) and azathioprine (3 mg/kg/day) from day −45 pre-transplant, and fludarabine (30 mg/m2/day) from day −16 through day −12. Conditioning regimen included oral or intravenous (i.v.) busulfan, thiotepa 10 mg/kg/day, cyclophosphamide 200 mg/kg total dose, and thymoglobulin 12.5-10 mg/kg total dose. Cyclosporine, methylprednisolone and methotrexate were given for GVHD prophylaxis. All but 4 patients received second HCT from the same donor. Thirteen patients received bone marrow (BM), and 8 patients PBSC. One patient was in class 1, 7 patients in class 2, and 13 patients in class 3 of risk. Most patients had moderately severe iron overload with median serum ferritin of 2692 ng/ml (range, 500-10126 ng/ml). The median liver fibrosis score 1 (range 0-5). Results. All but 1 patient achieved sustained engraftment with a 5 year overall and disease-free survival (DFS) of 85% (95% CI, 59-95%). DFS was 92% (95% CI, 54-99%) in patients receiving BM and 75% (95% CI, 32-93%) in those given PBSC, although the difference was not statistically significant (p=0.27) (Figure 1). One patient had primary GF with the cumulative incidence of 5% (95% CI, 0-13%). The incidence of grade 2-4 acute GVHD was 50% (95% CI, 0-75%) in the PBSC and 8 % (95% CI, 0-24%) in the BM group (p=0.025). Respective incidences of moderate to severe chronic GVHD were 43% (95% CI, 0-70%) and 0% (p=0.012). The high incidence of both acute and chronic GVHD after PBSC transplantation prompted us to abandon its use for second transplantation since 2006. At the time of survival analysis, 18 patients were alive, with median follow-up duration of 10 years (range, 1.2-12.8 years). At present all patients are off immunosuppressive medication. There were 3 deaths due to pneumonia, postsplenectomy sepsis and rejection with cerebral bleeding. The most frequently observed toxicities were grade 2 elevations in AST and ALT, followed by grade 2 oral mucositis. Few patients experienced grade 3 liver and gut toxicities. None of the patients developed liver VOD. Three patients had pneumonia, and 4 patients developed grade 2-3 late onset BK virus -related hemorrhagic cystitis. None of the patients developed lymphoproliferative disorder. Conclusions. We demonstrate the excellent DFS in patients with thalassemia treated with second transplantation for GF/R following the first graft. Importantly, the intensified treatment protocol was not associated with increased nonhematological toxicity, even though most patients suffer from pre-existing organ damage due to iron overload and/or hepatitis. This study clearly showed that the same donor could be successfully used for second transplantation in these patients. Due to significantly high incidence of both acute and chronic GVHD after PBSC, bone marrow graft is preferred source for second transplantation in patients with thalassemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals High incidence of graft failure in children receiving CD34+ augmented elutriated allografts for nonmalignant diseases

2003 ◽  
Vol 31 (12) ◽  
pp. 1073-1080 ◽  
Author(s):  
C H McDonough ◽  
D A Jacobsohn ◽  
G B Vogelsang ◽  
S J Noga ◽  
A R Chen
Keyword(s):  
Graft Failure ◽  
High Incidence

Post penetrating keratoplasty infectious keratitis: Clinico-microbiological profile and predictors of outcome

2021 ◽  
pp. 112067212110629
Author(s):  
Abhishek Dave ◽  
Sanil Sawant ◽  
Manisha Acharya ◽  
Arpan Gandhi ◽  
Atanu Majumdar ◽  
...  
Keyword(s):  
Graft Failure ◽  
Penetrating Keratoplasty ◽  
Surgical Intervention ◽  
Graft Infection ◽  
Multivariate Logistic Regression Analysis ◽  
Fungal Growth ◽  
Infectious Keratitis ◽  
Microbiological Profile ◽  
High Incidence ◽  
Graft Success

Purpose To study the clinico-microbiological profile, outcomes and prognostic factors of post penetrating keratoplasty (PKP) infectious keratitis. Methods Retrospective review of medical records of 78 patients with post PKP infectious keratitis presenting between January 2014 and December 2018. Demographic, clinical and microbiological profile was documented and predictors of treatment and graft success were evaluated using univariate and subsequent multivariate logistic regression analysis. Results Mean age of patients was 52.17 ± 15.51 years and mean infiltrate size was 19.39 ± 19.68 mm2. Mean duration of presentation with infection post PKP was 11.66 ± 10.65 months. Culture positivity was seen in 64 eyes (82.05%). Bacterial growth was observed in 47 eyes (60.25%), fungal growth in 17 (21.79%) and no microbiological growth in 14 eyes (17.94%). At 3 months the visual acuity (VA) improved in 37 eyes (47.44%), did not change in 27 (34.62%) and deteriorated in 14 (17.95%). Graft failure was noted in 53 eyes (73.08%). Surgical intervention was needed in 47 (60.25%) eyes of which most common was therapeutic PKP in 32 eyes (41.02%). Treatment failure was noted with fungal infection ( p = 0.05), poorer vision at presentation ( p = 0.02), larger infiltrate area ( p = 0.002) and graft infection developing before 1 year ( p = 0.02). Graft failure was noted with associated endophthalmitis ( p = 0.02), poorer VA at presentation ( p = 0.01) and larger infiltrate area ( p = 0.02). Conclusion Post PKP infectious keratitis is a sight threatening ocular condition. It is associated with high incidence of graft failure and frequently requires surgical intervention. Fungal etiology, larger infiltrate size, poorer vision at presentation and associated endophthalmitis carries a poorer prognosis.

The observation of defects on (100) CdTe surfaces by chemical etching

1992 ◽  
Vol 50 (2) ◽  
pp. 1424-1425
Author(s):  
M.E. Lee
Keyword(s):  
Single Crystal ◽  
Grain Boundaries ◽  
Single Crystals ◽  
Chemical Etching ◽  
Crystalline Perfection ◽  
Crystalline Defects ◽  
High Incidence ◽  
Crystallographic Defects ◽  
Cdznte Substrates ◽  
Device Technology

The crystalline perfection of bulk CdTe substrates plays an important role in their use in infrared device technology. The application of chemical etchants to determine crystal polarity or the density and distribution of crystallographic defects in (100) CdTe is not well understood. The lack of data on (100) CdTe surfaces is a result of the apparent difficulty in growing (100) CdTe single crystal substrates which is caused by a high incidence of twinning. Many etchants have been reported to predict polarity on one or both (111) CdTe planes but are considered to be unsuitable as defect etchants. An etchant reported recently has been considered to be a true defect etchant for CdTe, MCT and CdZnTe substrates. This etchant has been reported to reveal crystalline defects such as dislocations, grain boundaries and inclusions in (110) and (111) CdTe. In this study the effect of this new etchant on (100) CdTe surfaces is investigated.The single crystals used in this study were (100) CdTe as-cut slices (1mm thickness) from Bridgman-grown ingots.

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