scholarly journals Second Allogeneic Hematopoietic Stem Cell Transplantation for Post-Transplant Relapsed Acute Leukemia in Children - an EBMT PDWP Retrospective Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 912-912
Author(s):  
Isaac Yaniv ◽  
Aviva C. Krauss ◽  
Eric Beohou ◽  
Arnaud Dalissier ◽  
Selim Corbacioglu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prognostic Factor ◽  
Acute Leukemia ◽  
Pediatric Patients ◽  
Multivariate Analyses ◽  
Acute Leukemias ◽  
Hematopoietic Stem ◽  
Entire Cohort

Abstract Introduction Using the EBMT registry, we retrospectively analyzed outcomes for 373 pediatric patients who underwent second allogeneic transplant for relapsed acute leukemia at 120 centers in 32 countries, between the years 2004 and 2013, in an attempt to assess relapse, survival, GVHD and other outcomes, as well as identify factors correlating with prognosis in this cohort of patients. To our knowledge, this is the largest analysis of pediatric patients undergoing second allogeneic HSCT for relapsed acute leukemia to date. This allowed for an independent analysis of each disease, including 214 patients with ALL and 159 with AML. Patients and Methods Centers received a questionnaire completing data already available in the ProMISe database on patients between 0-18 years of age treated between 2004 and 2013. Results A total of 387 patients received a second SCT after relapse. 373 have been included in the analysis, 214 for ALL and 159 for AML. Detailed data were available for 201 patients from 48 centers; for the remainder, analysis was based on the registry. For the entire cohort overall survival (OS) at 2 and 5 years were 38% and 29%, and leukemia free survival (LFS) 30% and 25% respectively. ALL: With a median follow up from 2nd SCT of 36.4 months, OS at 1 and 5 years were 47% and 28% respectively. LFS was 39% and 28% respectively. NRM at 2 years was 22%. In multivariate analyses favorable prognostic factors for both OS and LFS were: CR prior to 2nd SCT (p=0.0001), interval > 12 months between transplants (p=0.0007), use of myeloablative conditioning (p=0.039) and the presence of cGvHD after the first SCT (p=0.0001). Good prognostic factor for low NRM was interval of more than 12 months between transplants (p=0.0002). AML: With a median follow up from 2nd SCT of 50 months, OS at 1 and 5 years were 44% and 15% respectively. LFS was 28% and 15% respectively. NRM at 2 years was 18%. In multivariate analyses, favorable prognostic factors for OS as well as LFS were: CR prior to 2nd SCT (p=0.031;0.044 respectively), interval > 6 months between transplants (p=0.0003;0.0001 respectively), and having cGvHD after the first SCT (p=0.0001). Most patients experience disease relapse or NRM within the first year after their second transplant. This observation seems to be more consistent in patients transplanted for ALL, with more changes over time in patients with AML. For ALL in particular, the 2-year incidences of relapse, NRM and LFS were not different from those at 5-years. Even in the relapse setting, survival rates for patients with ALL remain superior to patients with AML, consistent with the prognostic differences at diagnosis. Our findings, consistent for the AML and ALL subgroups, suggest that cGHVD prior to second HSCT is associated with better outcome. The identification of cGHVD prior to second transplant has not been heretofore described as a favorable prognostic factor. This strong correlation merits further study, specifically as to the underlying biology for this association. Conclusion Children with relapsed acute leukemias have a substantial chance to become long term survivors following a second SCT. CR prior to second SCT, longer interval between transplants and the presence of cGvHD after the first transplant, are favorable prognostic factors for ALL and AML. Our findings may help physicians in discussing the risk-benefit of a second transplant. These results are particularly relevant in an era where an explosion of new therapies, specifically targeted therapies and those that modulate the immune response, behoove us to carefully identify subpopulations of patients for whom specific therapies are appropriate. Novel approaches are needed to minimize relapse risk as well as short and long term morbidity in these pediatric patients while considering a second SCT for relapsed acute leukemia. Disclosures Corbacioglu: Jazz Pharmaceuticals: Consultancy, Honoraria. Bader: Novartis, Medac, Amgen, Riemser, Neovii: Consultancy, Honoraria, Research Funding.

scholarly journals Early Response Predicts Long-Term Improvement or Stabilization of Persons with Multiple Sclerosis Treated with Hematopoietic Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Iván Murrieta-Álvarez ◽  
Montserrat Rivera-Álvarez ◽  
Gilberto David Elias-de-la-Cruz ◽  
Luisa Fernanda Sánchez-Valledor ◽  
Carmina Alejandra Córdova-Ramírez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Logistic Regression ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Multivariate Analyses ◽  
Early Response ◽  
Hematopoietic Stem

Introduction: Hematopoietic stem cell transplantation (HSCT) has been widely employed for autoimmune disorders under myeloablative and non-myeloablative regimens. The main indication for HSCT in this setting is multiple sclerosis (MS) in its relapsing-remitting form and related disorders such as neuromyelitis optica or clinical isolated syndrome. Results have varied, but response rates and prognostic features are still unkown along the spectrum of disease and conditioning regimens. Methods: People with MS (PwMS) autografted from March 2015 to March 2020 with a reduced intensity regimen (Cy/G-CSF + Rituximab) (NCT 02674217), were followed longitudinally every 3 months to assess the Expandable Disease Status Scale (EDSS). All patients with complete follow-up data were included in this study and two different cohorts were made according to PwMS that were followed by 12 or 24 months. The primary outcome was improvement or stabilization of EDSS at 12 months and 24 months. All potential prognostic factors were collected from electronic medical record of patients with complete sociodemographic, clinical and laboratory data. In order to identify prognostic factors related to responses, univariate analyses were carried out with logistic regression; variables that showed a p value <0.15 were included in the multivariate analyses (using age, sex, type of MS, previous history of EDSS as covariates) with logistic regression. All patients signed a consent to authorize intervention and contact for follow-up and the protocol study was approved by the Institutional Ethics Committee. Results: Two cohorts were formed according to follow-up periods. Cohort 1 (12 months follow-up) comprised of 200 pwMS, 133 (66.5%) being female and 47 (33.5%) male. Their features are shown in Figure 1A. Cohort 2 (24 months follow-up) was formed by 93 pwMS, 60 (64.5%) being female and 33 (35.5%) male. Their features are shown in Figure 1B. In cohort 1, 149 pwMS (74.5%) had a response while 51 (25.5%) did not. Mean change of EDSS between baseline and 12 months post-HSCT was -0.42 (range -7 to 4). In cohort 2, 54 patients (58%) had a response while 39 (42%) did not. Mean change of EDSS between baseline and 24 months post-HSCT was -0.02 (range -4 to 7). In cohort 1, baseline EDSS ≥4 was identified as a predictor of 12 months response in multivariate analysis (OR 0.02, p 0.02, 95% CI 0.1- 0.8). Also, early response at 3 months post-HSCT in the univariate (OR 8.5, p <0.0001, 95% CI 3.9 - 18.4) and multivariate (OR 10.3, p <0.0001, 95% CI 4.6 - 23.2) analyses presented as a predictor of 12 months response. In cohort 2, early response at 6 months predicted response at 24 months post-HSCT in the univariate (OR 16.1, p <0.0001, 95% CI 4.8 - 53.6) and multivariate analysis (OR 28, p <0.0001, 95% CI 5.8 - 133.8). Furthermore, duration of disease >10 years showed an association with a negative response at 24 months as well in the univariate (OR 0.3, p 0.008, 95% CI 0.1 - 0.7) and multivariate analyses (OR 0.1, p 0.002, 95% CI 0.04 - 0.5). These results are shown in Figure 1C and 1D. Conclusions: Early response at 3 or 6 months may be robust measures that could translate in long term improvement or stabilization of disease. Although the effects showed in this study are profound and were replicated on two cohorts, these results should be interpreted with caution and a longer follow-up could confirm these findings. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of Pretransplant HTLV-1 Seropositivity on Hematopoietic Stem Cell Transplantation for the Diseases Other Than ATLL- an Analysis on Behalf of JSHCT Complication Working Group-

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4641-4641
Author(s):  
Nobuaki Nakano ◽  
Hideki Nakasone ◽  
Shigeo Fuji ◽  
Akihito Shinohara ◽  
Ritsuro Suzuki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factor ◽  
Cell Transplantation ◽  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Multivariate Analyses ◽  
Adult Patients ◽  
Cell Leukemia ◽  
Hematopoietic Stem ◽  
Serological Status

Abstract Background Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus which is known as the cause of adult T-cell leukemia/lymphoma (ATLL). Some reports indicated that HTLV-1 carriers were immunologically compromised host. Although there were several reports about the survival impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ATLL, no large study concerning HSCT for the HTLV-1 carrier with the diseases other than ATLL has been reported. Japan is one of endemic countries of HTLV-1, and the prevalence of HTLV-1 infection was reported to be almost 1% of Japanese population. On behalf of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) Complication Working Group, we here report the impact of HTLV-1 serological status on survival in those with HSCT for the diseases other than ATLL by using the Transplant Registry Unified Management Program (TRUMP) which is the nationwide survey database of the Japanese Data Center for Hematopoietic Cell Transplantation. Patients and Method There were 25840 patients (24400 adult and 1440 child), who had the information about the pretransplant serological status of HTLV-1, received their first HSCT between Jan 2007 and Dec 2015 in TRUMP database. We analyzed an overall survival (OS) and non-relapse mortality (NRM) after HSCT in relation to HTLV-1 serological status using Kaplan-Meir method, Gray's test. A Gray test for NRM calculated considering with disease related death as the competing risk. In multivariate analyses using Cox proportional hazard model for OS and Fine-Gray proportional hazards models for competing risk of NRM. And a p-value of less than 0.05 was considered as statistically significant. A statistical analysis was performed with 'EZR'. Results Median age of HTLV-1 carrier and non-carrier in adult patients were 57 years (17-76) and 53 years (16-88) and in pediatric patients were 11 years (0-15) and 8 years (0-15), respectively. The number of HTLV-1 carrier/non-carrier in adult patients in each disease were 80/7511 in AML, 133/6673 in malignant lymphoma, 34/3265 in plasma cell neoplasm, 30/2885 in ALL, 31/2178 in MDS, 8/446 in CML, 5/539 in aplastic anemia, and 11/570 in others, respectively. The number of HTLV-1 carrier/non-carrier in pediatric patients in each disease were 3/684 in ALL, 6/394 in AML, 2/170 in MDS, 2/76 in congenital metabolic disease, and 3/100 in others. The number of HTLV-1 carrier/non-carrier in adult patients who received allo-HSCT or auto-HSCT were 237/15777 and 95/8920, and in pediatric patients who received allo-HSCT was 16/1424, respectively. No HTLV-1 carrier child recipients who recieved auto-HSCT were identified in TRUMP database. There were no significant differences about stem cell sources, disease risk, and HCT-CI score before HSCT between HTLV-1 carriers and non-carriers. The OS rates at 3yr after allo-HSCT in adult and pediatric HTLV-1 carrier vs non-carrier were 40.7% vs. 50.2% (P=0.003) and 49.1% vs. 67.1% (P=0.318), and NRM rates at 1yr after allo-HSCT were 46.9% vs 23.6% (P=0.001) and 18.8% vs 11.7% (P=0.05), respectively. In multivariate analyses in terms of OS and NRM, HTLV-1 carrier was a significant prognostic factor in adult patients (HR 1.23, 95% CI 1.03-1.47, P‹0.001 for OS, and HR 1.27, 95% CI 1.05-1.61, P‹0.001 for NRM) and in pediatric patients (no statistical significance was seen on OS, and HR 2.58, 95% CI 1.17-5.70, P‹0.001 for NRM). The incidence of non-infectious NRM, such as pulmonary complications (IPS/DAH, ARDS), acute and chronic GVHD, MOF, and VOD/SOS was significantly higher in adult HTLV-1 carriers who received allo-HSCT when compared with that in HTLV-1 non-carriers. On the other hand, Infectious NRM was significantly higher incidence in child HTLV-1 carrier. With respect to disease related death, there were no differences between HTLV-1 carrier and non-carrier both in adult and pediatric patients. Among the adult patients who received auto-HSCT, there was no statistically significant difference in terms of OS, NRM, and disease related death between HTLV-1 carrier and non-carrier. Conclusion This is the first large study showing the survival impact of HTLV-1 serological status in patients with diseases other than ATLL who received HSCT. It demonstrated that HTLV-1 antibody-positivity was the poor prognostic factor in terms of OS and NRM after allo-HSCT in adult patients and NRM after allo-HSCT in pediatric patients. Disclosures Nakasone: Phizer: Honoraria; Novartis: Honoraria; Kyowa Hakko Kirin: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Suzuki:Kyowa-Hakko Kirin: Honoraria; Chugai Pharmaceutical: Honoraria; Mochida Pharmaceutical: Honoraria; Novartis: Honoraria; Shionogi: Honoraria; Takeda Pharmaceuticals: Honoraria; Meiji Seika Pharma: Honoraria; MSD: Research Funding; Ohtsuka: Honoraria; Sawai Pharmaceutical: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Gilead Sciences: Consultancy; MundiPharma: Consultancy; Jazz Pharmaceuticals: Consultancy.

scholarly journals Pediatric Aortic Valve Repair: Any development in the material for cusp extension valvuloplasty?

2021 ◽  
Author(s):  
Kelli Hu ◽  
Umar Siddiqi ◽  
Brian Lee ◽  
Emily Pena ◽  
Kelci Schulz ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Pediatric Patients ◽  
Long Term Outcomes ◽  
Aortic Cusp ◽  
Entire Cohort ◽  
Autologous Pericardium ◽  
Kaplan Meier ◽  
Short And Long Term

Background: Aortic cusp extension is a technique for aortic valve (AV) repairs in pediatric patients. The choice of the material used in this procedure may influence the time before reoperation is required. We aimed to assess post-operative and long-term outcomes of patients receiving either pericardial or synthetic repairs. Methods: We conducted a single center, retrospective study of pediatric patients undergoing aortic cusp extension valvuloplasty (N=38) with either autologous pericardium (n=30) or Cormatrix (n=8) between April 2009 and July 2016. Short and long-term postoperative outcomes were compared between the two groups. Freedom from reoperation was compared using Kaplan Meier analysis. Degree of aortic stenosis (AS) and aortic regurgitation (AR) were recorded at baseline, post-operatively, and at outpatient follow-up. Results: At five years after repair, freedom from reoperation was significantly lower in the CorMatrix group (12.5%) compared to the pericardium group (62.5%) (P = 0.01). For the entire cohort, there was a statistically significant decrease in the peak trans-valvar gradient between pre- and post-operative assessments with no significant change at outpatient follow-up. In the pericardium group, 28 (93%) had moderate to severe AR at baseline which improved to 11 (37%) post-operatively and increased to 21 (70%) at time of follow-up. In the biomaterial group, 8 (100%) had moderate to severe AR which improved to 3 (38%) post-operatively and increased to 7 (88%) at time of follow-up. Conclusion: In terms of durability, the traditional autologous pericardium may outperform the new CorMatrix for AV repairs using the cusp extension method.

The Power of Reiki: Feasibility and Efficacy of Reducing Pain in Children With Cancer Undergoing Hematopoietic Stem Cell Transplantation

2019 ◽  
Vol 36 (5) ◽  
pp. 361-368 ◽  
Author(s):  
Giulia Zucchetti ◽  
Filippo Candela ◽  
Cristina Bottigelli ◽  
Gabriela Campione ◽  
Annalisa Parrinello ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Pediatric Patients ◽  
Experimental Period ◽  
Hematopoietic Stem ◽  
Session Versus ◽  
Within Subjects

Purpose: Reiki is a growing complementary therapy in pediatric oncology that needs evidence to become more credible among the health community. A within-subject design experiment was conducted to pilot testing the feasibility and efficacy of Reiki to provide pain relief among pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Method: Pediatric patients undergoing HSCT during the inpatient phase in the Stem Cell Transplantation Unit were eligible to participate to the pilot study. Short and medium effects were assessed investigating the increase or decrease of patient’s pain during three specific time periods (“delta”) of the day: morning of the Reiki session versus assessment before Reiki session (within subjects control period), assessment before Reiki session versus assessment after Reiki session (within subjects experimental period) and assessment after Reiki session versus morning the day after Reiki session (within subject follow-up period). The long-term effects were verified comparing the pain evolution in the day of the Reiki session with the following rest day. Results: The effect of 88 Reiki therapy sessions in nine patients (Mage = 12; Female = 61%) was analyzed following a short, medium, and long-term perspective. Repeated-measures analysis of variance revealed a significant difference among the three periods ( F = 17,17 p < .0001): A decrease of the pain occurred in the experimental period in short and medium term, while in the follow-up period, the pain level remained stable. Conclusions: This study demonstrates the feasibility of using Reiki therapy in pediatric cancer patients undergoing HSCT. Furthermore, these findings evidence that trained pediatric oncology nurses can insert Reiki into their clinical practice as a valid instrument for diminishing suffering from cancer in childhood.

scholarly journals Long-Term Follow-Up of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

JBMTCT ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 142
Author(s):  
Júlia Lopes Garcia ◽  
Antonio Vaz de Macedo ◽  
Polliany Roberta Dorini Pelegrina ◽  
Rita de Cássia Barbosa Tavares ◽  
Roseane Vasconcelos Gouveia ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Marrow Transplantation ◽  
Pediatric Patients ◽  
Hematopoietic Stem ◽  
Long Term Follow Up ◽  
Long Term Survivors

Hematopoietic stem cell transplantation (HSCT) offers the opportunity for cure to patients with malignant and non-malignant diseases. Given the myriad advances in the past few decades, coupled with the rising numbers of transplants worldwide, the number of long-term survivors, many of whom are free of the disease for which they were transplanted, is constantly increasing. Despite the improved prognosis observed overall, long-term outcome may be undermined by transplant-associated morbidity and mortality. Long-term survivors may present a variety of complications, comprising physical, psychological, social, and economic arenas, with a deep impact on quality of life. Therefore, drawing greater attention to and raising awareness of the potential long-term effects of HSCT is key to providing a tailored approach to pretransplant counseling and to devising appropriate recommendations for post-transplant screening, prevention, and timely treatment of secondary events. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide updated, evidence-based guidance for the long- term follow-up of pediatric patients undergoing HSCT, the results of which are presented here.

scholarly journals Pediatric Aortic Valve Repair: Any development in the material for cusp extension valvuloplasty?

2021 ◽  
Author(s):  
Kelli Hu ◽  
Umar Siddiqi ◽  
Brian Lee ◽  
Emily Pena ◽  
Kelci Schulz ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Pediatric Patients ◽  
Long Term Outcomes ◽  
Aortic Cusp ◽  
Entire Cohort ◽  
Autologous Pericardium ◽  
Kaplan Meier ◽  
Short And Long Term

Background: Aortic cusp extension is a technique for aortic valve (AV) repairs in pediatric patients. The choice of the material used in this procedure may influence the time before reoperation is required. We aimed to assess post-operative and long-term outcomes of patients receiving either pericardial or synthetic repairs. Methods: We conducted a single center, retrospective study of pediatric patients undergoing aortic cusp extension valvuloplasty (N=38) with either autologous pericardium (n=30) or CorMatrix (n=8) between April 2009 and July 2016. Short and long-term postoperative outcomes were compared between the two groups. Freedom from reoperation was compared using Kaplan Meier analysis. Degree of aortic stenosis (AS) and aortic regurgitation (AR) were recorded at baseline, post-operatively, and at outpatient follow-up. Results: At five years after repair, freedom from reoperation was significantly lower in the CorMatrix group (12.5%) compared to the pericardium group (62.5%) (P = 0.01). For the entire cohort, there was a statistically significant decrease in the peak trans-valvar gradient between pre- and post-operative assessments with no significant change at outpatient follow-up. In the pericardium group, 28 (93%) had moderate to severe AR at baseline which improved to 11 (37%) post-operatively and increased to 21 (70%) at time of follow-up. In the biomaterial group, 8 (100%) had moderate to severe AR which improved to 3 (38%) post-operatively and increased to 7 (88%) at time of follow-up. Conclusion: In terms of durability, the traditional autologous pericardium may outperform the new CorMatrix for AV repairs using the cusp extension method.

scholarly journals Surgical outcomes in spinal cord ependymomas and the importance of extent of resection in children and young adults

2014 ◽  
Vol 13 (4) ◽  
pp. 393-399 ◽  
Author(s):  
Michael Safaee ◽  
Michael C. Oh ◽  
Praveen V. Mummaneni ◽  
Philip R. Weinstein ◽  
Christopher P. Ames ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Radiation Therapy ◽  
Prognostic Factor ◽  
Pediatric Patients ◽  
Extent Of Resection ◽  
Tumor Location ◽  
Grade Ii ◽  
The Mean

Object Ependymomas are a common type of CNS tumor in children, although only 13% originate from the spinal cord. Aside from location and extent of resection, the factors that affect outcome are not well understood. Methods The authors performed a search of an institutional neuropathology database to identify all patients with spinal cord ependymomas treated over the past 20 years. Data on patient age, sex, clinical presentation, symptom duration, tumor location, extent of resection, use of radiation therapy, surgical complications, presence of tumor recurrence, duration of follow-up, and residual symptoms were collected. Pediatric patients were defined as those 21 years of age or younger at diagnosis. The extent of resection was defined by the findings of the postoperative MR images. Results A total of 24 pediatric patients with spinal cord ependymomas were identified with the following pathological subtypes: 14 classic (Grade II), 8 myxopapillary (Grade I), and 2 anaplastic (Grade III) ependymomas. Both anaplastic ependymomas originated in the intracranial compartment and spread to the spinal cord at recurrence. The mean follow-up duration for patients with classic and myxopapillary ependymomas was 63 and 45 months, respectively. Seven patients with classic ependymomas underwent gross-total resection (GTR), while 4 received subtotal resection (STR), 2 received STR as well as radiation therapy, and 1 received radiation therapy alone. All but 1 patient with myxopapillary ependymomas underwent GTR. Three recurrences were identified in the Grade II group at 45, 48, and 228 months. A single recurrence was identified in the Grade I group at 71 months. The mean progression-free survival (PFS) was 58 months in the Grade II group and 45 months in the Grade I group. Conclusions Extent of resection is an important prognostic factor in all pediatric spinal cord ependymomas, particularly Grade II ependymomas. These data suggest that achieving GTR is more difficult in the upper spinal cord, making tumor location another important factor. Although classified as Grade I lesions, myxopapillary ependymomas had similar outcomes when compared with classic (Grade II) ependymomas, particularly with respect to PFS. Long-term complications or new neurological deficits were rare. Among patients with long-term follow-up, those who underwent GTR had a recurrence rate of 20% compared with 40% among those with STR or biopsy only, suggesting that extent of resection is perhaps a more important prognostic factor than histological grade in predicting PFS, which has been suggested by other data in the literature. Given the relative paucity of these lesions, collaborative multiinstitutional studies are needed, and such efforts should also focus on molecular and genetic analysis to refine the current classification system.

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