Effects of second transplantation with T-cell-replete haploidentical graft using low-dose anti-thymocyte globulin on long-term overall survival in pediatric patients with relapse of leukemia after first allogeneic transplantation

2021 ◽  
Author(s):  
Shogo Kobayashi ◽  
Hideki Sano ◽  
Kazuhiro Mochizuki ◽  
Yoshihiro Ohara ◽  
Nobuhisa Takahashi ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Low Dose ◽  
Pediatric Patients ◽  
Allogeneic Transplantation ◽  
Second Transplantation

Long-Term Follow-up of Patients With Multiple Myeloma Who Received Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2154-2154
Author(s):  
Michele L. Donato ◽  
David S Siegel ◽  
David H. Vesole ◽  
Phyllis McKiernan ◽  
Themba Nyirenda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Cumulative Incidence ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematopoietic Stem ◽  
Unrelated Donors

Abstract Allogeneic transplantation for multiple myeloma (mm), although seen as potentially curative, has inherent treatment-related mortality and long-term implications. Important questions remain such as the expectation for long-term survival and the role, if any, of the graft versus tumor effect. The study cohort included 56 consecutive patients (pts) with mm who received an allogeneic hematopoietic stem cell transplant (HSCT) between November 9, 2004 and June 1st 2011. Only pts who had received at least one prior autologous transplant were included in this retrospective analysis. Patients received either a non-myeloablative (NMA), a reduced intensity (RIC) or an ablative (MA) regimen. The NMA regimen consisted of low dose TBI for siblings and low dose TBI with fludarabine for unrelated donors. The RIC regimen was fludarabine melphalan, with the addition of low dose thymoglobulin for unrelated donors. The MA regimen was busulfan and melphalan, with thymoglobulin for unrelated donors. A favorable group of 26 pts received their allogeneic transplantation for consolidation after demonstrating a response (PR, VGPR, CR) to their prior autograft and without evidence of progression, leaving 30 pts in the salvage transplant group defined as pts unresponsive (less than PR) or with relapse after their prior autograft. The median age was 52.4 years (SD = 6.9 years). Twenty six (46%) pts were female. The hematopoietic cell donors were 35 siblings and 21 unrelated (URD). In the URD group, 10 (47.6%) pts had a mismatched donor. In our cohort 10 (17.9%) pts received a MA, 22 (39.3%) received a RIC and 24 (42.9%) received a NMA regimen. The median follow-up was 52 months. The related and unrelated donor cohorts were similar except for age (53.9 years versus 49.8 years p = 0.03). Overall, 32 (57.1%) pts achieved a CR. Seven (12.5%) pts had a VGPR, 13 (23.2%) had a PR and 2 (3.6%) had stable disease. At the time of analysis, 49.2% of pts were in CR. Twenty one (37.5%) pts relapsed post transplantation of whom 16 received donor lymphocytes (DLI 15 pts) or immune suppression withdrawal (1 pt), with 10 (62.5%) pts responding to this intervention. The cumulative incidence of acute GVHD (aGVHD) grade II-IV was 35.4%, 28.6% for related donors and 47.6% for URD (p = 0.16). The cumulative incidence of chronic GVHD (cGVHD) was 50%, 52% for related donors and 43% for URD (p=NS). The number of non-relapse deaths (NRM) was 13 (23.2%). The cumulative incidence of NRM at 1 year was 18.2%, and 25.5% at 5 years. In the multivariate model, number of prior autologous HSCT (1 vs >1) and grade III-IV aGVHD were significantly associated with an increased NRM. The overall survival (OS) for all 56 pts was 59% at 5 years. The OS at 5 years for the 30 pts who received transplantation as salvage (refractory to the prior autograft or relapsed after the prior autograft), was 38% compared to 82% for the consolidation group. The univariate analysis indicates that pts receiving their allogeneic transplantation as salvage, disease status prior to allogeneic HSCT, number of prior auto HSCT, aGVHD, response post allo HSCT and cGVHD were significantly associated with the risk of all cause mortality, with cGVHD being protective. Donor type (URD versus related), adverse cytogenetics, preparative regimen and age were not significant predictors of risk for all cause mortality by univariate analysis.Overall survival salvage (yes) vs consolidation group (no)Overall survival salvage (yes) vs consolidation group (no)Overall survival pts with (yes) or without (no) chronic GVHDOverall survival pts with (yes) or without (no) chronic GVHD Multivariate analysis shows OS significance for being in the salvage group (HR 4.05, p=0.0196), a GVHD (HR 2.99, p=0.034) and cGVHD (HR 0.26, p=0.012), the latter being protective. The PFS for all 56 pts was 38% at 5 years, 57% for the consolidation group and 21% for the salvage group. In conclusion, patients with multiple myeloma can have an excellent overall survival following allogeneic transplantation even in the setting of relapsed or refractory disease to a prior auto HSCT. Unrelated donors performed just as well as matched siblings. Acute GVHD was deleterious to OS, whereas chronic GVHD was significantly associated with improvement in OS supporting the role of a graft versus tumor effect in multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

A Comparison of Ventriculoperitoneal and Ventriculoatrial Shunts in a Population of 544 Consecutive Pediatric Patients

Neurosurgery ◽  
2019 ◽  
Vol 87 (1) ◽  
pp. 80-85 ◽  
Author(s):  
George N Rymarczuk ◽  
Robert F Keating ◽  
Daniel J Coughlin ◽  
Daniel Felbaum ◽  
John S Myseros ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pediatric Patients ◽  
Older Children ◽  
Long Term Outcomes ◽  
Single Institution ◽  
First Line ◽  
Pediatric Hydrocephalus ◽  
Csf Shunting ◽  
Similar Survival

Abstract BACKGROUND Although ventriculoperitoneal shunts (VPS) remain the first-line option in most instances of pediatric hydrocephalus, the long-term efficacy of ventriculoatrial shunts (VAS) remains unknown. OBJECTIVE To characterize the long-term outcomes and adverse occurrences associated with both VPS and VAS at our institution. METHODS The authors retrospectively analyzed all cerebrospinal fluid (CSF) shunting procedures performed over a 13-yr period at a single institution. A total of 544 pediatric shunt patients were followed for at least 90 d (VPS: 5.9 yr; VAS: 5.3 yr). RESULTS A total of 54% of VPS and 60% of VAS required at least 1 revision. VPS demonstrated superior survival overall; however, if electively scheduled VAS lengthening procedures are not considered true “failures,” no statistical difference is noted in overall survival (P = .08). VPS demonstrated significantly greater survival in patients less than 7 yr of age (P = .001), but showed no difference in older children (P = .4). VAS had a significantly lower rate of infection (P < .05) and proximal failure (P < .001). CONCLUSION VAS can be a useful alternative to VPS when the abdomen is unsuitable, particularly in older children. Although VPS demonstrates superior overall survival, it should be understood that elective VAS lengthening procedures are often necessary, especially in younger patients. If elective lengthening procedures are not considered true failures, then the devices show similar survival.

scholarly journals Long‐Term Protease Inhibitor–Containing Therapy Results in Limited Improvement in T Cell Function but Not Restoration of Interleukin‐12 Production in Pediatric Patients with AIDS

2001 ◽  
Vol 184 (2) ◽  
pp. 201-205 ◽  
Author(s):  
Claire Chougnet ◽  
Shirley Jankelevich ◽  
Keith Fowke ◽  
David Liewehr ◽  
Seth M. Steinberg ◽  
...  
Keyword(s):  
T Cell ◽  
Protease Inhibitor ◽  
Pediatric Patients ◽  
Cell Function ◽  
Interleukin 12 ◽  
T Cell Function

Outcome and Immune Reconstitution Following T Cell Depleted Nonmyeloablative Allogeneic Transplantation Using Matched Donors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2036-2036 ◽  
Author(s):  
David A. Rizzieri ◽  
Liang Piu Koh ◽  
Gwynn D. Long ◽  
Cristina Gasparetto ◽  
Jerald Z. Gong ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Immunosuppressive Agents ◽  
Allogeneic Transplantation ◽  
Stable Phase ◽  
Immune Recovery ◽  
Post Transplant ◽  
Donor Cells

Abstract To minimize toxicity and monitor immune recovery without interference of long term use of immunosuppressive agents, we have investigated T-cell depleted, nonmyeloablative allogeneic therapy using matched family member donors. Methods: Seventy five patients who were not candidates for ablative therapy due to age or comorbid diseases received fludarabine 30mg/sq m and cyclophosphamide 500mg/sq m IV qd x 4 with alemtuzumab 20mg IV qd x 5 followed by stem cell infusion. No other post transplant immunomodulation was provided. Results: Patient diagnoses included lymphoma/myeloma (20), leukemias/MDS (30), myelofibrosis/aplasia (7) and metastatic solid tumours (18). The median age was 50 (range 18–17) with a median follow up of 18 months. The median CD34+ cell dose collected was 13.4 x 106/kg. Engraftment occurred in 100% of patients with a median of 97% donor cells responsible for patient hematopoiesis by 3 months. Forty six also had a DLI (range 106–108 CD3+ cells/kg). Overall, Grade III–IV acute GVHD occurred in only 5/75 (7%) and 18 (29%) had grade II–IV. Four patients developed chronic GVHD. The transplant regimen was well tolerated with 4% 100 day treatment related mortality. In those with hematologic malignancies, only 7% started in remission, though 45 (60%) attained a CR. The most common cause of death in this group was progressive disease (28%), followed by infections (5%), and GVHD (5%). A subgroup of 21 of these older, more infirm patients who had high risk AML in 1–2nd CR or PR or ≥2 chronic stable phase CML, partially responding lymphoma, or severe myelofibrosis have been followed for at least 1 year. At 1 year, 13/21 (62%) remain alive and in continuing remission. Phenotypic analysis of lymphocyte subsets (measured by flow) revealed recovery at 6 months. Figure Figure T cell VBeta family recovery (spectratype analysis using PCR) revealed robust recovery by 6 months as well (first figure pre and second is 6 months post transplant), despite T depletion. Figure Figure TRECs analysis reveals little, if any, recovery in these patients for at least 12–18 months. Conclusions: Nonablative allogeneic transplantation using alemtuzumab for T cell depletion results in reliable engraftment with little acute GVHD or TRM. Immune recovery assays reveal that despite T cell purging, T cell subset and VBeta families have significant recovery by 6 months and TRECS results show the recovery is primarily from peripheral expansion of transplanted donor cells, not education of new T cells. These data possibly reflect the advantage of low dose donor lymphocyte boosts without planned long term use of immunosuppressive agents. The future challenge will to be to develop strategies to further improve immune recovery in this setting.

Long Term Clinical Outcomes in Patients with Massive Splenomegaly and Non-Hodgkin's Lymphoma Treated with Splenectomy.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2692-2692 ◽  
Author(s):  
Jacob Smeltzer ◽  
Thomas M Habermann ◽  
Taner Timucin ◽  
David Nagorney ◽  
Kay Ristow ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Clinical Outcomes ◽  
Hodgkin’S Lymphoma ◽  
Median Overall Survival ◽  
Hodgkin's Lymphoma ◽  
Massive Splenomegaly ◽  
Abdominal Symptoms ◽  
Non Hodgkin's Lymphoma

Abstract Abstract 2692 Background: Massive splenomegaly is occasionally encountered in patients with Non-Hodgkin's Lymphoma (NHL) and can be associated with abdominal symptoms, anemia and thrombocytopenia. The spleen may also be a primary focus of the disease itself. Splenectomy offers the benefit of localized treatment of the disease as well as relief of symptoms from splenomegaly and associated cytopenias. The safety and long term clinical outcomes of splenectomy for massive splenomegaly (>1500 gm) in patients with various histologies of NHL was analyzed. Methods: Data was obtained from clinical records of 90 patients with a diagnosis of NHL who underwent a splenectomy at Mayo Clinic Rochester from January 1998 to December 2007. Demographics, previous treatments, histology, post- surgical complications were collected and analyzed for the entire cohort. Additionally, median overall survival, improvement in symptoms, anemia and thrombocytopenia were analyzed by NHL type. Results: Median age at splenectomy was 67 years (range 42–84 yrs.) and 56 (62%) of patients were male. Average time from diagnosis to splenectomy was 3 months (range 0–217 months). Splenectomy was the first treatment in 56 (62%) patients; the other 34 patients were treated with chemotherapy with an average of two previous regimens. Most patients had involvement outside of the spleen, 65 (72%) with concurrent bone marrow involvement and 35 (50%) with lymph node involvement. Various different NHL histologies were represented: marginal zone (MZ) (34%), mantle cell (MC) (26%), diffuse large B-cell lymphoma (DLBCL) (10%), follicular (FL) (11%), lymphoplasmacytic (LP) (6%) and T cell NOS (4%). With a median follow-up time of 25 months, the median overall survival differed by histology type of NHL (Table 1). Indolent lymphomas such as FL, LP and MZ had more favorable survival compared with more aggressive lymphomas such as DLBCL and T cell NOS. Splenectomy was safe and well tolerated with only one treatment related death. There were no reported post-splenectomy septic events. Two patients did develop a portal vein thrombosis. 95% of patients had relief in pressure and abdominal symptoms post-splenectomy. With the exception of patients with DLBCL and T-cell NHL, a majority of patients had improvement in anemia and thrombocytopenia related to splenomegaly (Table 2). Conclusions: This represents the largest reported series of patients with lymphoma treated with splenectomy. Our results indicate that median overall survival after splenectomy is determined by the underlying type of NHL. Patients with LP, FL, MZ and MCL have a favorable outcomes following splenectomy. Splenectomy remains a safe and effective treatment option for massive splenomegaly in selected patients during the course of their disease management. Disclosures: No relevant conflicts of interest to declare.

Ex Vivo T Cell-Depleted Haploidentical HCT for Children with Acute Leukemia after a Reduced-Intensity Preparative Regimen Containing Low-Dose TBI

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4673-4673
Author(s):  
Yeon Jung Lim ◽  
Ho Joon Im ◽  
Sung Han Kang ◽  
Hyery Kim ◽  
Kyung-Nam Koh ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Leukemia ◽  
Low Dose ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Reduced Intensity

Abstract Background: Recent advances in haploidentical hematopoietic cell transplantation (HHCT) enabled this transplant using haploidentical family donor to be a viable option for pediatric patients lacking matched related or unrelated donor. In our center, HHCT using ex vivo T cell-depleted (TCD) grafts after reduced-intensity conditioning (RIC) was conducted since 2008. The safety and efficacy of this transplantation modality for pediatric with acute leukemia were investigated. Methods: Thirty-one pediatric patients with acute leukemia received ex vivo T cell-depleted HHCT at Asan Medical Center Children's Hospital between July 2008 and June 2016. Four patients received CD3-depleted grafts and 27 received TCRαβ-depleted stem cells. Among 31 patients, 9 had ALL (3 CR1, 6 CR2-3), 22 had AML (18 CR1-3, 4 NR). Seven patients had relapsed after previous allogeneic HCT. All 31 patients underwent a uniform RIC regimen consisting of low-dose total body irradiation (LD-TBI; 600 cGy), fludarabine (FLU; 180 mg/m2), cyclophosphamide (CY; 100 mg/kg), and rabbit anti-thymocyte globulin (r-ATG; 3 mg/kg). Results: The median age at HHCT was 14 years (range, 1-19). All 31 patients achieved sustained neutrophil engraftment at a median of 10 days (range, 9-17) post-transplant. The cumulative incidence of acute GVHD grade II-III and III were 30% and 21%, respectively. None developed grade IV. Two of 26 evaluable patients developed extensive chronic GVHD. As of July 2016, 18 of the 31 patients survive free of disease with a median follow-up of 26 months (range, 2-98 months). Ten patients have died. Causes of death were relapse (n=9) and disseminated tuberculosis (n=1). Only one patient died of non-relapse cause, leading to TRM of 5.3% at 1 year. EFS and OS at 2 years for all patients were 51% and 60%, respectively. Sixteen patients with AML who received a first HHCT in any CR showed a favorable outcome (EFS of 85%), whereas, 6 patients with ALL who received a first HHCT in CR showed a poor EFS of 28%. In addition, all patients (6 with AML and 3 with ALL) who received a subsequent HCT in CR or were not in remission developed relapse. Conclusions: This study demonstrated that our ex vivo T cell-depleted HHCT using RIC is a feasible therapy with low TRM for pediatric patients with acute leukemia. The outcome of patients with AML who received their first transplant in CR was excellent in this treatment modality. However, the outcome of ALL was poor suggesting that more intensified conditioning regimen may be required for those diseases. Furthermore, an innovative treatment strategy is warranted to improve the outcome for patients with relapsed or refractory acute leukemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals 41: Long-term follow up of T cell depleted transplants from unrelated donors in pediatric patients

2007 ◽  
Vol 13 (2) ◽  
pp. 18 ◽  
Author(s):  
G.A. Hale ◽  
R.A. Krance ◽  
S.P. Khan ◽  
R. Rochester ◽  
E.M. Horwitz ◽  
...  
Keyword(s):  
T Cell ◽  
Pediatric Patients ◽  
Long Term Follow Up ◽  
Unrelated Donors

Advances in therapies for non-Hodgkin lymphoma in children

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 522-528 ◽  
Author(s):  
Rachel Kobos ◽  
William Terry
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Pediatric Patients ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Newly Diagnosed ◽  
Limited Data ◽  
Non Hodgkin Lymphoma ◽  
Short And Long Term

Pediatric patients with newly diagnosed, non-Hodgkin Lymphoma (NHL) have an excellent overall survival. However, therapy regimens are associated with acute toxicity and late effects. Furthermore, patients with relapsed or refractory disease have relatively few options with proven clinical benefit. Both histologic and molecular differences exist between adult and pediatric NHL preventing simple translation of adult NHL successes into improvements in pediatric NHL treatment. This review summarizes the introduction of targeted therapies into frontline treatments for patients with anaplastic large-cell lymphoma and CD20–positive tumors, with the goal of improving overall survival while limiting both short- and long-term toxicities. In addition, newer approaches that have limited data in children but may have a significant role in how we treat pediatric NHL in the future are reviewed, which include CD19 directed therapy, Notch inhibition, the tri-functional antibody, FBTA05, and EZH2 inhibition.

scholarly journals Incidence and Outcomes of Pediatric Myelodysplastic Syndrome in the US

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1285-1285
Author(s):  
Ana Xavier ◽  
Matthew A. Kutny ◽  
Luciano J Costa
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndrome ◽  
Pediatric Patients ◽  
De Novo ◽  
The United States ◽  
Refractory Anemia ◽  
Histological Subtype ◽  
Risk Of Death

Background There is lack of epidemiological data on pediatric myelodysplastic syndrome (p-MDS) in the literature. MDS became reportable to the Surveillance, Epidemiology and End Results (SEER) Program in 2001, providing an opportunity to estimate the incidence and survival of pediatric patients with MDS in the United States. Methods We utilized data from the National Cancer Institute SEER-18 to determine the incidence and long term overall survival (OS) of pediatric patients (ages 0 to 20 years) diagnosed with de novo MDS or therapy-related MDS. Inclusion criteria was diagnosis of MDS (International Classification of Diseases-Oncology, Third Edition, ICD-O-4 codes 9980/3, 9991/3, 9992/3, 9982/3, 9985/3, 9983/3, 9986/3, 9986/3, 9989/3, 9985/3, 9975/3, and 9987/3) between 2001 and 2011. Follow up was updated through the end of 2011 (November 2013 submission). Overall survival was estimated using the method of Kaplan-Meier. A Cox proportional hazard model was used to compare the effects of age, race, gender, histological subtype, and etiology (de novovs. therapy-related) on survival. Results The incidence of p-MDS was 1.16 cases/1 million population*year. A greater incidence occurred in children younger than 1 year of age possibly reflecting congenital bone marrow failure syndromes (Figure 1). A total of 314 p-MDS cases were included in the analysis with median follow up of 31 months (range 0-131). Median age of patients was 9 years; 167 (53.3%) had MDS unclassifiable (NOS), 40 (12.7%) had therapy-related MDS (t-MDS), 44 (14%) had refractory anemia with excess blasts (RAEB), 32 (10.3%) had refractory anemia (RA), 17 (5.4%) had refractory cytopenia with multilineage dysplasia (RCMD), 6 (1.9%) had refractory anemia with ring sideroblasts (RARS), 5 (1.6%) had refractory anemia with excess blasts in transformation (RAEBT), and 3 (0.9%) had MDS associated with isolated del(5q). Male patients comprised 154 (49%) of cases. Racial groups included white (218, 69.4%), 52 (15.7%) black, 37 (11.8%) of other races, and 7 (2.3%) the race was unknown. The 5 year-OS for the entire cohort was 68% (95% C.I.=62.3-73.7). Patients with t-MDS had significantly worse 5 year-OS (41.2%; 95%C.I.=23.8-58.6) compared to those with de novo MDS (71.3%; 95%C.I.=65.3-77.2; P=0.004, Figure 2). In multivariate analysis of age, race, gender, histological subtype, and etiology (de novovs. therapy-related) utilizing Cox regression model, only t-MDS was associated with higher risk of death (HR=2.07, 95% C.I.=1.25-3.42, P=0.005). Conclusions Pediatric MDS is a rare disorder, with higher incidence among children younger than 1 year of age. Over two thirds of p-MDS patients will become long-term survivors, although significantly inferior outcome is seen in t-MDS. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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