scholarly journals Impact of megatherapy on survival after relapse from stage 4 neuroblastoma in patients over 1 year of age at diagnosis: a report from the European Group for Bone Marrow Transplantation.

1993 ◽  
Vol 11 (12) ◽  
pp. 2330-2341 ◽  
Author(s):  
R Ladenstein ◽  
C Lasset ◽  
O Hartmann ◽  
D Frappaz ◽  
A Garaventa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Proportional Hazards ◽  
Bone Marrow Involvement ◽  
Marrow Transplant ◽  
Cox Proportional Hazards ◽  
Age At Diagnosis ◽  
Conventional Dose ◽  
Stage 4 ◽  
Group A ◽  
Group B

PURPOSE Relapse from stage 4 neuroblastoma usually carries a poor prognosis. A retrospective study using the European Bone Marrow Transplant (EBMT) Solid Tumor Registry was undertaken to define the role of megatherapy (MGT) in relapsed patients. PATIENTS AND METHODS After relapse, 33 boys and 15 girls with previous stage 4 neuroblastoma received intensification by MGT followed by either autologous (n = 42) or allogeneic (n = 6) bone marrow rescue in 11 European institutions. The median age at diagnosis was 47 months (range, 14 to 134) and the median interval from diagnosis to relapse was 16 months (range, 4 to 94). Thirty patients had received only conventional-dose primary treatments (group A), whereas 18 patients had previously received intensification with MGT (group B). The median follow-up time of the total group is 95 months (range, 25 to 185). RESULTS The actuarial overall survival rate at 2 years after MGT for relapse is 27% for group A and 0% for group B (P = .02). Three adverse, independent prognostic factors were confirmed by multivariate analysis using the Cox proportional hazards regression model: an interval of less than 12 months between diagnosis and relapse (P < .0001), nonresponding or untreated relapse (P = .0002), and previous MGT during primary treatments (P = .055). None of the other variables analyzed, such as sex, age, bone or bone marrow involvement at diagnosis or at relapse, and type of MGT at relapse, influenced outcome in this patient cohort. CONCLUSION Responding patients who relapse more than 12 months from diagnosis who had not received previous MGT appear to benefit from consolidation MGT. Relapse patients who do not fulfill these criteria gain no advantage from this cost-intensive procedure and should be treated differently.

Clinical features, molecular aberrations, treatments, and outcomes in histiocytic sarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7020-7020
Author(s):  
Gordon Ruan ◽  
Gaurav Goyal ◽  
Nabila Nora Bennani ◽  
Mithun Vinod Shah ◽  
Karen Rech ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Bone Marrow Involvement ◽  
Cox Proportional Hazards ◽  
Histiocytic Sarcoma ◽  
Braf V600e ◽  
Variable Response ◽  
Kaplan Meier ◽  
Multifocal Disease

7020 Background: Histiocytic sarcoma (HS) is a rare and aggressive malignancy of the monocyte/macrophage lineage. There is a paucity of data on treatments and outcomes in HS. Methods: This is a retrospective study of patients with histologically confirmed diagnosis of HS from 2000-2018. Kaplan-Meier and log-rank tests were used to perform overall survival (OS) analyses. Hazard ratios (HR) with confidence intervals (CI) were calculated using Cox-proportional hazards. Results: There were 27 patients in the study (median age 59; range 3-83) and 63% were males. Nine had unifocal involvement and 18 had multifocal disease. Common sites involved were lymph node (50%), soft tissue (40%), bone (36%), and bone marrow (22%). Two of 8 patients had the BRAF-V600E mutation. Next-generation sequencing was performed on 8 patients and showed ≥1 oncogenic alterations (DNMT3A, FLT4, KRAS, NRAS, NUP98, PTCH1, PTPN11, TP53, TSC1, PDGFR, or BRAF genes) as well as a CLIP2-BRAF fusion. The median OS for the cohort was 12 months. Factors associated with worse OS included multifocal disease (OS 10 vs. 125 months, p = 0.03; HR 5.0, CI 1.1-21.8) and marrow involvement (OS 3 vs. 43 months, p = 0.003; HR 8.9, CI 1.7-45.0). Twelve (44%) had surgery with median OS of 42 months (range 1-125). Fifteen had chemotherapy with median OS of 12 months (range 2-67; Table). Conclusions: HS is an aggressive neoplasm, with multifocal disease and bone marrow involvement portending worse outcomes. Most patients have somatic oncogenic alterations involving the MAPK-ERK pathway and other genes. Chemotherapeutic regimens have variable response rates but are not durable. More studies on targeted kinase inhibitors in HS are needed to improve outcomes. [Table: see text]

Extension of bone marrow involvement and cytopenias in patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 222-222
Author(s):  
Daniel D Almeida Preto ◽  
Marcella de Oliveira Gonçalves Prince Soares ◽  
Wilson Eduardo Furlan Matos Alves ◽  
Marcos Alves de Lima ◽  
Joao Antonio Junior Neif ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prognostic Factor ◽  
Bone Marrow Involvement ◽  
Bone Lesions ◽  
Castration Resistant Prostate Cancer ◽  
Event Free Survival ◽  
Free Survival ◽  
Castration Resistant ◽  
Group A ◽  
Group B

222 Background: Most of bone metastatic castration-resistant prostate cancer (mCRPC) patients present variable extension of bone marrow involvement which in some cases may influence hematopoiesis. Cytopenias may hinder clinical practice, especially in decision making, regarding the use of myelotoxic drugs. The aim of this study was to assess whether the extension of bone marrow involvement in mCRPC patients is a prognostic factor for developing cytopenias. Methods: We retrospectively reviewed 1649 hemograms from 103 bone mCRPC cases. Patients were pooled in two groups, according to the extension of bone metastasis assessed by skeletal scintigraphy: ≤10 lesions (group A) and >10 lesions or superscan (group B). Time for cytopenia event (event-free survival) and overall survival (time from first cytopenia event until death) were calculated using the Kaplan-Meier method and differences between survivals were tested using the log-rank test. Univariable analysis were performed to determine any significant prognostic factor. Results: The median event-free survival (EFS) was longer in patients with ≤10 bone lesions (group A) on the margin of significance (41.9 vs 23.6 months; p=0.051). The exploratory analyses for severe cytopenia events (grade 3-4) also showed a longer EFS for group A (51.8 vs 31.7 months; p=0.050). When group B was stratified into two subgroups (11-20 bone lesions vs >20 or superscan), there was no significant difference in EFS (19.1 vs 24.2 months; p=0.14). The median overall survival (OS) was 3.3 (1.9-4.6) months, regardless the extension of bone involvement. Patients in the group with more bone lesions showed higher mean PSA levels (55.5 vs 40.3 ng/mL; p=0.01). ECOG, stage disease, Gleason score, visceral metastases, types of cytopenia event (anemia, neutropenia or thrombocytopenia), number of chemotherapy lines, and antialgic radiotherapy did not show difference between groups. Conclusions: The extension of bone metastasis in mCRPC seems to be a prognostic factor for developing cytopenias, but is not related to OS. Additional analyzes with a larger sample are needed to assess whether any clinical variables may be associated with cytopenia event.

scholarly journals History of stroke is a major factor to affect prognosis of elderly chronic limb-threatening ischemia patients with frailty after endovascular therapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Kanda ◽  
Y Ikeda ◽  
T Sonoda ◽  
K Anzaki ◽  
R Arikawa ◽  
...  
Keyword(s):  
Endovascular Therapy ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Geriatric Medicine ◽  
Cox Proportional Hazards ◽  
Medicine Research ◽  
History Of ◽  
Group A ◽  
Hs Crp ◽  
Group B

Abstract Background Chronic limb-threatening ischemia (CLTI) is the most advanced form of severe arteriosclerosis, and CLTI patients are known to have poor prognosis due to complication of polyvascular diseases, including cerebrovascular disease. Stroke often causes disability of exercise, leading to develop frailty and sarcopenia, and frailty and sarcopenia are known to important factors affecting the prognosis of cardiovascular disease. However, the effect of history of stroke for clinical outcomes in elderly CLTI patients with frailty has not been well evaluated. Purpose The aim of the present study was to investigate whether a history of stroke affects prognosis of elderly CLTI patients with frailty after endovascular therapy (EVT). Methods The subject was 228 consecutive elderly (≥65 year) CLTI patients underwent EVT. These patients had frailty with clinical frailty scale 5 or 6 or 7 which was defined by Geriatric Medicine Research. Clinical frailty was assessed on admission before procedure of EVT by physicians or other health professionals. The study patients were divided into two groups based on patients with or without history of stroke group (Group A and B). We investigated the association between history of stroke on admission and outcome after EVT. Results All-cause death ≤6 month and ≤12 month after EVT were 10 cases (4%) and 19 cases (8%). Group A had higher rate of all-cause death ≤6month and ≤12 month (14 vs. 3%, p=0.012, 19 vs. 6%, p=0.019) than those of Group B. Kaplan Meier analysis elucidated that survival rate was significantly lower in Group A compared to that in Group B (p=0.031). As a result of cox proportional hazards analysis, all-cause death ≤6 month was associated with history of stroke [hazard ratio (HR): 5.07, 95% confidence interval (CI): 1.47–17.52, p=0.010)], hs-CRP (HR: 1.09, 95% CI: 1.01–1.16, p=0.010) in the univariate analysis. Similarly, cox proportional hazards analysis for revealed that history of stroke (HR: 3.02, 95% CI: 1.19–7.68, p=0.020), hs-CRP (HR: 1.09, 95% CI: 1.03–1.14, p&lt;0.001), hemodialysis (HR: 2.53, 95% CI: 1.03–6.24, p=0.043), use of clopidogrel (HR: 0.22, 95% CI: 0.07–0.78, p=0.019) and serum albumin level (HR: 0.40, 95% CI: 0.21–0.80, p=0.008) were significantly associated with all-cause death ≤12 month. Multivariate analysis models after adjusted for the demographic characteristics of patients and clinically relevant factors for all-cause death ≤6 month and ≤12 month after EVT revealed that history of stroke was an independent risk factor (HR: 5.18, 95% CI: 1.44–17.43, p=0.011, HR: 2.98, 95% CI: 1.71–7.61, p=0.022). Conclusions These data suggested that history of stroke was a crucial independent predictor for incidence of all-cause death in elderly CLTI patients with frailty. Funding Acknowledgement Type of funding source: None

scholarly journals Efficacy and safety of 5-fluorouracil in infrared monitor guided bleb revision

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rumi Kawashima ◽  
Kenji Matsushita ◽  
Ryo Kawasaki ◽  
Kohji Nishida
Keyword(s):  
Proportional Hazards ◽  
Anterior Segment ◽  
Significant Risk ◽  
Cox Proportional Hazards ◽  
Subconjunctival Injection ◽  
Success Rates ◽  
Additional Surgery ◽  
Group A ◽  
Group B

Abstract Purpose Infrared monitor-guided bleb revision (IRGBR), an alternative needling system, visualizes anterior-segment tissues around the bleb not visible during needle revision after trabeculectomy. This study determined the safety and efficiency of 5-fluorouracil (5-FU) as an adjunctive anti-metabolite in IRGBR. Methods We retrospectively analyzed 43 consecutive eyes (40 patients; 14 eyes, primary open-angle; 29 eyes, secondary glaucoma) treated with IRGBR for failing filtering blebs. The patients were divided into two groups. The first one had IRGBR without adjunctive 5-FU subconjunctival injection, and the second one had IRGBR with 5-FU. We performed Kaplan-Meier survival analysis using log-rank tests after 2 years of follow-up and Cox proportional hazards regression model to analyze the dependence of the survival time on predictor variables. Two failure criteria were defined as the need for additional surgery for intraocular pressure (IOP) reduction and the IOP at two consecutive follow-up visits based on definition 1, IOP ≧22 mmHg and definition 2, IOP ≧17 mmHg. Results Thirty eyes (29 cases) underwent IRGBR with subconjunctival 5-FU injection (group A in the second term) and 13 eyes (11 cases) without 5-FU (group B in the first term). The success rates 24 months after IRGBR were 73.3 and 23.1%, respectively, in groups A and B based on the definition 1 failure and 56.7 and 7.7% based on the definition 2 failure. Complications included transient bleb leaks (group A, 3 eyes; group B, none) and choroidal detachment (group A, 1 eye; group B, none). No use of 5-FU and IOPs ≧10 mmHg 1 week after IRGBR were significant risk factors. Conclusions Adjunctive 5-FU in IRGBR achieved a better success rate for failing trabeculectomy blebs.

Abstract 16430: Risk Factors Associated With Worsening Left Ventricular Function Post-bone Marrow Transplant in Multiple Myeloma Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jim Chen ◽  
Tanya Sharma ◽  
Fuad Habash ◽  
Emily Sanders ◽  
Abdullah Malkawi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Transplant ◽  
Proportional Hazards ◽  
Systolic Function ◽  
Marrow Transplant ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Lv Function

Background: New onset or worsening congestive heart failure (CHF) poses a significant challenge in multiple myeloma (MM) patients post bone marrow transplant (BMT). The aim of this study was to determine co-morbidies that increased the risk of worsening left ventricular (LV) function post-BMT. Methods: Retrospective study looking at MM patients between 2013 to 2019 with at least 1 bone marrow transplant. The primary end point was the time from BMT to >10% worsening ejection fraction (EF) noted on echocardiogram, compared to baseline values. A Cox proportional hazards regression model was used to create hazard ratios. Results: A total of 524 patients with diagnosis of MM were included who had at least 1 BMT with an average follow up time of 309.3 days. Prior hospitalizations of heart failure prior to BMT significantly increased the risk of developing reduced systolic function post transplant (HR 6.38 [95% CI 2.07 - 19.63]). Other contributing factors for reduced EF include: elevated BMI, history of hypertension, liver disease, peripheral vascular disease, stroke, and lenalidomide prior to BMT. Conclusion: This study was able to identify prognostic factors contributing to worsening heart failure.

Effects of spaceflight on rat erythroid parameters

1996 ◽  
Vol 81 (1) ◽  
pp. 117-122 ◽  
Author(s):  
Z. Allebban ◽  
L. A. Gibson ◽  
R. D. Lange ◽  
T. L. Jago ◽  
K. M. Strickland ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Life Sciences ◽  
Lower Number ◽  
Ground Control ◽  
Colony Forming Unit ◽  
Human Erythropoietin ◽  
Group A ◽  
Group B ◽  
First Time ◽  
Group D

Hematologic studies were performed on 21 ground control rats and 21 rats flown during the Spacelab Life Sciences-2 14-day mission. Group A (n = 5) was used to collect blood in flight and 9 days postflight, group B (n = 5) was injected with recombinant human erythropoietin (rhEpo), group C (n = 5) received saline as a control, and group D (n = 6) was killed in flight and tissues were collected. Results indicated no significant changes in peripheral blood erythroid elements between flight and ground control rats. The nonadherent bone marrow on flight day 13 showed a lower number of recombinant rat interleukin-3 (rrIL-3)-responsive and rrIL-3 + rhEpo-responsive blast-forming unit erythroid (BFU-e) colonies in flight rats compared with ground control rats. On landing day, a slight increase in the number of rhEpo + rrIL-3-responsive BFU-e colonies of flight animals compared with ground control rats was evident. Nine days postflight, bone marrow from flight rats stimulated with rhEpo alone or with rhEpo + rrIL-3 showed an increase in the number of colony-forming unit erythroid colonies and a decrease in BFU-e colonies compared with ground control rats. This is the first time that animals were injected with rhEpo and subsequently blood and tissues were collected during the spaceflight to study the regulation of erythropoiesis in microgravity.

scholarly journals 849. Reduced CIED Infections with an Antibacterial Envelope: Microbiologic Analysis of the WRAP-IT Study

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S16-S16 ◽  
Author(s):  
Muhammad R Sohail ◽  
G Ralph Corey ◽  
Bruce L Wilkoff ◽  
Jeanne Poole ◽  
Suneet Mittal ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
De Novo ◽  
Electronic Device ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Cardiac Resynchronization ◽  
Control Group ◽  
Group A ◽  
Suppressive Antibiotic Therapy ◽  
To Receive

Abstract Background Cardiovascular implantable electronic device (CIED) infections are associated with significant morbidity, mortality, and cost. There is limited evidence on antibiotic prophylactic strategies to prevent CIED infection. Recently, the TYRX Envelope, which elutes a combination of rifampin and minocycline for a minimum of 7 days, was shown to significantly reduce major CIED infections in the WRAP-IT trial. We sought to characterize the pathogens among patients who experienced an infection in the current era. Methods All patients undergoing CIED replacement, upgrade, revision, or de novo cardiac resynchronization therapy (CRT-D) received standard of care antibiotic prophylaxis and were randomized 1:1 to receive TYRX or not. The primary endpoint was major CIED infection within 12 months of the procedure. Major infection was defined as an infection resulting in (1) system extraction or revision, (2) long-term suppressive antibiotic therapy, or (3) death. Data were analyzed using the Cox proportional hazards regression model. Results A total of 6,983 patients were randomized worldwide with 3,495 randomized to receive an envelope and 3,488 randomized to the control. At 12 months, 25 major infections (0.7%) were observed in the envelope group and 42 major infections (1.2%) in the control group, resulting in a 40% reduction of major infections (HR: 0.60, 95% CI: 0.36–0.98, P = 0.04). Of 63 infections assayed, causative pathogens were identified in 36 infections whereas cultures were negative in 27 cases. Staphylococcus species (n = 22) were the predominate pathogens and a 53% reduction was observed with the use of TYRX (Figure 1). Moreover, there was only 1 CIED pocket infection with Staphylococcus species in the envelope group compared with 14 pocket infections in the control group. A comparison of timing of infection in the envelope group showed the presence of 11 endocarditis/bacteremia infections at 103 ± 84 days compared with 14 pocket infections presenting at 70 ± 78 days from the procedure. Conclusion In this large randomized trial, the use of the TYRX Envelope containing rifampin and minocycline resulted in a significant reduction of major CIED infections and was effective against staphylococcal species, which are the predominant cause of pocket infections. Disclosures All Authors: No reported Disclosures.

Bone Marrow Transplantation or G-CSF Treatment Can Accelerate Recovery of Injured Spinal Cord in Mice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4181-4181
Author(s):  
Damianos Sotiropoulos ◽  
Eleni Siotou ◽  
Evangelia Athanasiou ◽  
Christos Kalpouzos ◽  
Panayotis Kaloyannidis ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Control Group ◽  
Significant Difference ◽  
Cord Injury ◽  
Group A ◽  
B Mice ◽  
The Mean ◽  
Group B

Abstract Mice, unlike rats and humans, have a self recovery mechanism of spinal cord injury. Whether the hematopoietic system is involved in this mechanism is under investigation. In this study we tested whether bone marrow cells transplanted or mobilized by a growth factor in mice with spinal cord injury, can accelerate the recovery. C57bl/6 female mice 10 to 12 weeks of age underwent spinal cord incision in an open operation. The injury was performed as a complete transection including the dura mater and the whole circumference of the cord at the T10-T11 intervertebral space with a micro scalpel (No 11). Group A mice received 200μg/kg/day G-CSF subcutaneously for 7 days, starting 24 hours after operation. Group B mice received 106 light density bone marrow cells from C576bl/6 donor mice intravenously 24 hours after operation. Control group mice received no treatment. Histological evaluation was performed at 48 hours, 1 week, 3 weeks and 5 weeks postoperatively. Paraffin embedded longitudinal samples of spinal cord were cut as serial sections. Spinal cord damage was estimated by measuring the maximum diameter of the area of axonal damage and disruption of astrocytic network using immunostaining for neurofilaments and GFAP. Antibodies against CD68 were applied to identify macrophage aggregations. All measurements were performed by morphometric photo analysis. The volume of fibroblastic infiltration was estimated using a grading system (0–7), based on Van Gieson stain for connective tissue. Functional deficits and recovery over time were evaluated by testing hind limb reflex and coordinated motor function (Kuhn and Wrathal functional tests, modified by Seki et al, 2002). All tests have been videotaped. Outcome scores at 48 hours, 1 week, 3 weeks and 5 weeks postoperatively for the control group, group A and group B mice were analyzed with the Mann-Whitney U test. 48 hours post operatively all mice in all groups were paralyzed in both hind limbs. Gradual improvement was observed in all groups. At week 3 there was a significant difference between the mean scores of functional tests for both treated groups (A and B) compared with the mean scores of the control group. Statistically significant difference (p&lt;0,05) was observed in 5 out of 7 tests for group A and in 3 out of 7 tests for group B. Same difference between Group A mice and control group mice was observed by 5 weeks, while group B had no statistically significant difference. No animal in any of the groups had a complete recovery 5 weeks postoperatively. Spinal cord in control group mice showed a gradually increase of fibroblastic infiltration until 5 week which entirely separated the two ends of the cord. In group A and group B mice a significant decrease of fibroblastic infiltration was observed at week 5 compared with week 3. Macrophage aggregations were evident at weeks 1 and 5 but not at week 3 in all groups. In conclusion our results indicate that light density bone marrow transplanted cells or G-CSF treatment can accelerate spinal cord injured mice recovery. It is possible that this is associated with a decrease in fibroblastic infiltration of spinal cord. Macrophage aggregation may also play an important role in the mechanism of recovery in mice, while in rats a different reaction including cavitation and delayed demyelination prohibits neurological recovery.

Study on Gene Exppression Profiling Associated with Prognosis in AML (M2a).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4360-4360
Author(s):  
Fan Yi Meng ◽  
Jiaming Tang ◽  
Wenli Ma
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Oligonucleotide Microarrays ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Group A ◽  
Group B ◽  
Refractory Aml

Abstract Objective: to explore genes related to the prognosis of AML (M2a). Methods: 6 newly diagnosed AML were involved in this experiment and were divided into 2 groups. Group A: 3 AML (M2a) patients with continuous complete remission (CCR1) less than 6 months; Group B: 3 AML (M2a) patients with CCR1 more than 12 months. Bone marrow mononuclear cells were separated and mRNA was purified and labeled with Cy3 and Cy5 respectively, which were used to hybridize against the Agilent human 1B 60mer oligonucleotide microarrays. Results: in the 20173 genes tested, 22 genes were found to be expressed differently between these two groups, among them 10 genes were up-regulated in group A, and 12 genes were up-regulated in group B. Conclusion: with microarray assay, 22 genes including APP were found to be differently expressed in AML (M2a) treated with standard chemotherapy. These genes may be early indicators for the diagnosis as well as prognosis of the refractory AML.

A Comparison of Clinical Outcomes of Non-T-Cell-Depleted (Non-TCD) Unrelated Donor Heamatopietic Stem Cell Transplantation (HSCT) and Non-TCD Haploidentical Related Donor HSCT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5140-5140
Author(s):  
Feng Chen ◽  
De Pei Wu ◽  
Aining Sun ◽  
Xiao Ma ◽  
Xiaowen Tang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Acute Gvhd ◽  
Peripheral Blood Stem Cell ◽  
Ex Vivo ◽  
Unrelated Donor ◽  
Group A ◽  
Related Donor ◽  
Group B

Abstract Unrelated donor HSCT and haploidentical related donor HSCT have been evaluated as alternative transplant options for the approximately 70% of patients without an HLA-identical sibling donor. To compare the clinical outcomes between Non-TCD unrelated donor HSCT and Non-TCD haploidentical HSCT, we studied 55 patients with high-risk or advanced leukemia who underwent Non-TCD HSCT from unrelated or haploidentical related donors from June 2001 to May 2006. Group A including 25 patients received HLA-matched unrelated donor HSCT, group B, including the other 30 patients, received HLA-haploidentical family donor HSCT. 20 recipient/donor pairs were allele matched and 5 pairs were 1–2 alleles disparity mismatched in the group A, HLA-haploidentical family donors in the group B included mother (22 cases), sibling(5 cases) and offspring (3 cases). Patients with myeloid leukemia were conditioned with the regimen consisting of Simustine (MeCCNU) 250mg/m2×1day, Ara-c 4g/ m2×2days, busulfan (Bu) 4mg/kg×3days, and cyclophosphamide (Cy)1.8g/m2×2days, patients with lymphoblastic leukemia were conditioned with the regimen consisting of MeCCNU 250mg/m2×1day, total-body irradition(TBI) 8Gy×1day, Ara-c 4g/ m2×2days, and Cy 1.8g/m2×2days. 15 patients received Non-TCD bone marrow transplantation (BMT), and 10 patients received Non-TCD peripheral blood stem cell transplantation (PBSCT) in the group A. 17 patients received G-CSF-primed bone marrow grafts that had not been depleted ex vivo of T cells, and 13 patients received G-CSF-primed bone marrow grafts plus G-CSF-mobilized peripheral blood stem cell without ex vivo T cell depletion in the group B. Prophylaxis against GVHD was performed with cyclosporine (CSP), short-term methotrexate (MTX), and mycophenolate mofetil (MMF), some patients received the combination of CSP, MTX and MMF plus antithymocyte globulin (ATG). When GVHD developed, methylprednisolone(MP) was given at first, if the response was poor, anti-CD25 monoclonal antibody was given to the patients as quickiy as possible and CSP was replaced with tacrolimus. All patients of the group A and 29 patients of the group B were engrafted successfully. Acute GVHD grades III-IVoccurred in 10 and 11 patients in the group A and B, respectively(the cumulaitive incidence 40% vs 37.9%, P&gt;0.05). 2 patients relapsed in each group (the actuarial probilities of relapse 8% vs 6%, P&gt;0.05). The 2-year probabilities of event-free survival(EFS) for the group A and B were (58.7±5.9)% and (42.2±2.0)%, respectively (P&gt;0.05). 10 patients of the group A and 17 of the group B died of transplantation- related disease. The primary causes of death included severe acute GVHD and pulmonary infection. These results suggested that both Non-TCD unrelated donor HSCT and Non-TCD haploidentical related donor HSCT are effective treatments for patients with refractory or high-risk hematologic malignancies, the high transplantation related mortality due to GVHD and infection is still a major challenge.

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