scholarly journals IMMU-08. MODELING UPFRONT GLIOBLASTOMA SURGICAL RESECTION AND STEROID USE REVEALS IMMUNOSUPPRESSIVE CHANGES AND SUGGESTS THAT PERIPHERAL LYMPHOCYTE COUNTS ARE ASSOCIATED WITH TUMOR VOLUME AND PROGNOSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii106-ii106
Author(s):  
Balint Otvos ◽  
Tyler Alban ◽  
Matthew Grabowski ◽  
Defne Bayik ◽  
Robert Winkelman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Surgical Resection ◽  
Cd8 T Cells ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Peripheral Lymphocyte ◽  
Steroid Use ◽  
Free Survival ◽  
Steroid Administration

Abstract Glioblastoma (GBM) and its treatment produces systemic immunosuppression, which is being targeted by immunotherapies. However, it remains unclear how surgical resection and steroids specifically in GBM alter the immune system. To further explore this issue, immunocompetent C57Bl/6 mice were intracranially inoculated with syngeneic glioma cells (GL261 and CT-2A) and growth of tumors was evaluated by MRI. Host immune cell populations were analyzed during surgical resection and steroid administration. Mice with surgically resected tumors had a longer median survival compared to mice subjected to tumor biopsies, and had increased bone marrow sequestration of both CD4 and CD8 T cells with corresponding decreased blood lymphocytes. Furthermore, physiologic doses of dexamethasone administered perioperatively decreased tumor edema, but increased the number and proliferative capacity of both marrow and circulating MDSCs while generating no survival benefit. Independent of therapy or dexamethasone, intracranial tumor volume correlated linearly with decreased CD4 and CD8 T cells in peripheral blood, and increased T cell sequestration within the bone marrow. We validated these parameters in steroid-naïve newly diagnosed GBM patients and observed decreased lymphocytes correlated linearly with increased tumor volume. When initial lymphocyte counts in both steroid-naïve and steroid-administered patients were used in univariate and multivariate models predicting progression-free survival and overall survival, decreased initial lymphocyte counts were an independent predictor of decreased progression free survival and decreased overall survival, with steroid use and initial tumor size falling out of significance during stepwise selection. Taken together, tumor volume is linearly correlated with marrow sequestration of lymphoid cells, but both surgery and steroid administration further suppress active immune responses along lymphoid and myeloid lineages. Furthermore, decreasing peripheral lymphocyte counts at diagnosis of GBM indicate an immune system less able to mount responses to the tumor and portent a worse progression free and overall survival.

Clinical Experience with Azacitidine In Chronic Myelomonocytic Leukemia (CMML) in Spain

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5040-5040
Author(s):  
Pablo Gonzalez Navarro ◽  
Regina García Delgado ◽  
Alicia Bailén Garcia ◽  
Juan Antonio Múñoz Múñoz
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Clinical Trials ◽  
Clinical Experience ◽  
Peripheral Blood ◽  
Progression Free Survival ◽  
Complete Response ◽  
Chronic Myelomonocytic Leukemia ◽  
Free Survival ◽  
Myelomonocytic Leukemia

Abstract Abstract 5040 Clinical Experience with Azacitidine In Chronic myelomonocytic leukemia (CMML) in Spain Pablo González Navarro 1*, Regina García Delgado 2*, Alicia Bailén Garcia 3*, Juan Antonio Muñoz Muñoz 4* 1MD, PhD. Hospital San Cecilio, 18014 Granada, Spain, Teléfono: 958023600 [email protected]; 2Hospital Virgen De La Victoria, Málaga, Spain; 3Hospital Carlos Haya, Málaga, Spain; 4MD, PhD. Hospital Universitario Puerta del Mar, Cádiz, Spain Introduction: Chronic myelomonocytic leukemia (CMML) is a clonal disorder of hematopoietic stem cells often occurring in elderly patients. In the new WHO classification, CMML has been reclassified as a myelodysplastic/myeloproliferative disease. CMML has been subdivided in two subclasses: CMML-1:<5% blasts in peripheral blood and 5–9% blasts in bone marrow, and CMML-2: <10% blasts in peripheral blood and 10–19% blasts in bone marrow (Greco et al. Mediterr J Hematol Infect Dis.2011). Azacitidine (AZA) is an hypomethylating agent approved in Europe for the treatment of myelodysplastic syndromes, with an intermediate to high risk of progressing to AML or death; chronic myelomonocytic leukemia (CMML) and AML that has developed from a myelodysplastic syndrome (prescribing information EMEA 2011). Until its approval in May 2009, AZA was used in Spain under compassionate use in clinical trials. AZA produce a direct decrease of DNA methyltransferase activity, reverting aberrant DNA methylation and increasing the expression of silenced genes, leading to celular differentiation and/or apoptosis (Greco et al. Mediterr J Hematol Infect Dis. 2011). Materials and Methods: We report the results of a retrospective, longitudinal, multicenter Spanish study of 27 patients to assess the effectiveness of AZA to treat CMML. We present results of: Response, Overall Response, Overall Survival and Progression Free Survival. Results: Eighteen of the patients (69.23%) had Chronic Myelomonocytic Leukemia (CMML) type 1 and nine (30.77%) CMML type 2. Median age at diagnosis was 69 years. Male/female ratio: 19/8. ECOG performance status score 1–2 was 78%, twenty patients (74%) received an initial dose of 75 mg/m2 of AZA, whereas three patients (11%) received 50mg/ m2. The mean number of cycles received was 8.32, 95%IC (5.91; 10.73). Overall response to treatment was 53% (CR+PR+HI+mCR): 14.81% complete response, 7.4% partial response, 3,7% Medular complete response and 29,62% Hematological Improvement. In addition, 18,51% had stable disease. Thirty-six percent of patients were alive at the end of treatment with AZA. Median Overall Survival and Progression Free Survival were 17.47 months (95%CI 9.33, upper limit not reached) and 10.97 (95%IC 3.97, 17.47) respectively (Figure 1, 2). Conclusion: Our results show that AZA is an active drug in the treatment of patients with CMML, with similar response rates in the published literature. More data from this study and further investigation with different clinical trials are needed to confirm these outcomes as well as safety and effectiveness of this treatment. Disclosures: García Delgado: Celgene and Novartis: Speakers Bureau.

Cyclin D1 Immunohistochemistry Identifies a Subset of Plasma Cell Myeloma with Superior Overall Survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4854-4854
Author(s):  
James R. Cook ◽  
Eric D. Hsi ◽  
Raymond R. Tubbs ◽  
Sarah Worley ◽  
Mohamad A. Hussein
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Plasma Cell ◽  
Plasma Cells ◽  
D1 Protein ◽  
Progression Free Survival ◽  
Plasma Cell Myeloma ◽  
Free Survival ◽  
Cyclin D1 Protein

Abstract The expression of Cyclin D1 is dysregulated in approximately half of cases of plasma cell myeloma due to translocations, aneusomy, or other abnormalities. Recent studies using quantitative mRNA analysis have suggested that increased Cyclin D1 mRNA expression is associated with a favorable prognosis. Previous attempts to examine the significance of cyclin D1 protein expression by immunohistochemistry have been hampered by the use of antibodies with weak staining and high background. In this study, we employ a newly available, commercial antibody that gives superior staining in B5 fixed tissues. We performed immunohistochemistry for Cyclin D1 on bone marrow core biopsies from a series of 44 newly diagnosed plasma cell myeloma patients who were uniformly treated on a Phase II study of rituxan, melphalan and prednisone. 22 patients (50%) were positive for Cyclin D1, defined as any plasma cells with positive nuclear staining. Cyclin D1 positive and negative cases displayed no significant differences in the initial levels of β2m (3.6±0.5 mg/L vs. 3.5±0.5 mg/L, p=0.860), number of bone marrow plasma cells (63±5.5% vs. 47±6.2%, p=0.063), or proportion of cases classified as SWOG stage 3-4 (2 of 22 (9%) vs. 5 of 22 (23%), p=0.412). The cyclin D1 positive cases displayed a superior overall survival with an estimated 3-year survival of 95% for Cyclin D1 positive cases versus 56% for Cyclin D1 negative cases (p=0.032). The cyclin D1 positive cases also displayed a trend towards better progression-free survival (median progression free survival of 15.7 months for Cyclin D1 positive versus 12.8 months for Cyclin D1 negative, p=0.13). In a Cox proportional hazards regression model, used to compare the effect of Cyclin D1 protein expression on overall survival time while adjusting for stage, the Cyclin D1 positive patients continued to show a strong trend to better overall survival (p=0.062). This study demonstrates that cyclin D1 immunohistochemistry, which could be readily performed in most pathology laboratories, is capable of identifying a subset of plasma cell myeloma with a favorable survival. Additional studies are ongoing to determine if these results can be generalized to other forms of therapy. If confirmed, routine cyclin D1 immunohistochemistry at the time of diagnosis may offer important prognostic information that could identify lower risk patients for whom less intensive therapies might be appropriate.

scholarly journals TACE Combined with HIFU Versus Surgical Resection for Single Hepatocellular Carcinoma with Child-Pugh B Cirrhosis in Overall Survival and Progression-Free Survival: A Retrospective Study

2021 ◽  
Vol 20 ◽  
pp. 153303382110601
Author(s):  
Qiwei Zhang ◽  
Yunbing Wang ◽  
Junyong Zhang ◽  
Wenfeng Zhang ◽  
Jianping Gong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Retrospective Study ◽  
Surgical Resection ◽  
Progression Free Survival ◽  
Tumor Diameter ◽  
Recurrence Rates ◽  
Free Survival ◽  
Resection Group ◽  
Small Hcc

Objective: To compare the effectiveness, safety and survival outcome of transcatheter arterial chemoembolization (TACE) combined with high-intensity focused ultrasound (HIFU) versus surgical resection for treating single hepatocellular carcinoma (HCC) with Child-Pugh B cirrhosis. Methods: A hospital-based retrospective study with 146 patients diagnosed with single HCC with Child-Pugh B cirrhosis from July 2010 to July 2018 was conducted in a tertiary teaching hospital. A total of 49 patients underwent TACE combined with HIFU (the combined group), and 97 patients underwent surgical resection (the resection group). Of them, 22 patients undergoing TACE combined with HIFU and 45 patients undergoing surgical resection had small HCC (tumor diameter ≤3 cm). The overall survival (OS) time, progression-free survival (PFS) time and postoperative complications were compared between the two groups. Results: In the single HCC tumor cohort, there was no significant difference in OS between the two groups [hazard ratio (HR) = 0.6379; 95% confidence interval (95% CI) = 0.3737 to 1.089; P = .0995], while the resection group showed an obvious superiority to the combined group regarding PFS (HR = 0.3545; 95% CI = 0.2176-0.5775; P < .0001). The 1-year, 3-year and 5-year recurrence rates were 30.9%, 55.7%, 86.6% in the resection group and 53.1%, 77.6%, 89.8% in the combined group, respectively. In the small HCC tumor cohort, there was also no difference in OS between the two groups (HR = 0.8808; 95% CI = 0.3295-2.355; P = .06396), while the resection group showed an obvious superiority to the combined group regarding PFS (HR = 0.4273; 95% CI = 0.1927-0.9473; P = .0363). The 1-year, 3-year and 5-year recurrence rates were 28.9%, 53.3%, 93.3% in the resection group and 40.9%, 68.2%, 81.8% in the combined group, respectively. Furthermore, the incidence of complications of the combined group was 38.8%, which was significantly less than the 56.7% of the resection group ( P = .041), and the duration of general anesthesia in the combined group was shorter than that in the resection group ( P = .001). Therein, there was no difference in the incidence of grade I complications (Clavien-Dindo classification) between the two groups ( P = .866). Conclusion: For patients with single or single small HCCs, TACE combined with HIFU may not be inferior to surgical resection in terms of the long-term survival rate, while surgical resection still has a definite advantage in terms of delaying recurrence. In addition, the combination of TACE and HIFU has higher safety than surgical resection.

Comparison of 5-aminolevulinic acid and sodium fluorescein for intraoperative tumor visualization in patients with high-grade gliomas: a single-center retrospective study

2020 ◽  
Vol 133 (5) ◽  
pp. 1324-1331 ◽  
Author(s):  
Rasmus W. Hansen ◽  
Christian B. Pedersen ◽  
Bo Halle ◽  
Anders R. Korshoej ◽  
Mette K. Schulz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Volume ◽  
Fluorescent Dyes ◽  
Aminolevulinic Acid ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Sodium Fluorescein ◽  
High Grade ◽  
Free Survival ◽  
High Grade Gliomas

OBJECTIVEMaximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, progression-free survival, and overall survival; and 2) to assess the influence of other risk factors on clinical outcome and screen for potential disadvantages of the dyes.METHODSA total of 209 patients with high-grade gliomas were included in this retrospective study. Resections were performed in the period from 2012 to 2017 using 5-ALA or fluorescein. Extent of resection was assessed as the difference in tumor volume between early postoperative and preoperative MRI studies. Tumor progression–free survival and overall survival were analyzed using an adjusted Cox proportional hazards model.RESULTSOne hundred fifty-eight patients were operated on with 5-ALA and 51 with fluorescein. The median duration of follow-up was 46.7 and 21.2 months, respectively. Covariables were evenly distributed. There was no statistically significant difference in volumetrically assessed median extent of resection (96.9% for 5-ALA vs 97.4% for fluorescein, p = 0.46) or the percentage of patients with residual tumor volume less than 0.175 cm3 (29.5% for 5-ALA vs 36.2% for fluorescein, p = 0.39). The median overall survival was 14.8 months for the 5-ALA group and 19.7 months for the fluorescein group (p = 0.06). The median adjusted progression-free survival was 8.7 months for the 5-ALA group and 9.2 months for the fluorescein group (p = 0.03).CONCLUSIONSFluorescein can be used as a viable alternative to 5-ALA for intraoperative fluorescent guidance in brain tumor surgery. Comparative, prospective, and randomized studies are much needed.

scholarly journals Clinical Outcome of Hypomethylating Agents in Hypocellular MDS: Mayo Clinic Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5254-5254
Author(s):  
Sonia Cerquozzi ◽  
Hassan B Alkhateeb ◽  
Moritz Binder ◽  
Darci Zblewski ◽  
Shahrukh K Hashmi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Median Time ◽  
Cytogenetic Analysis ◽  
Research Funding ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Hypomethylating Agents ◽  
Free Survival ◽  
Very High

Abstract Introduction: Hypocellular myelodysplastic syndrome (h-MDS) represents only a small portion of MDS, of which, the clinical significance and outcomes are not well understood. Both laboratory and clinical evidence suggests that h-MDS shares immune-mediated pathogenic mechanisms similar to acquired aplastic anemia. As a result, immunosuppressive therapy (IST) has been the mainstay treatment. Since h-MDS is poorly understood and reported response rates to IST vary, we retrospectively reviewed the outcome of our patients with hypocellular MDS and identified the effectiveness of alternative therapy using hypomethylating agents (HMA). Methods: AllMDS patients over a 13-year period (June 1997 to May 2010) were captured after an IRB approval was obtained. Patients' demographics, labs, bone marrow aspirates and biopsies as well as cytogenetic data were collected. We used the currently accepted age-adjusted criteria to define hypocellularity as ≤ 30% in patients <70 years old, and ≤20% in >70 years old. Only patients with available response data were included in the final analysis. Survival estimates were calculated using Kaplan-Meier curves. Results: We identified 65 (8%) h-MDS patients from a cohort of 827 adult MDS. Median age was 68 years (range, 20-90), with 69% males. The largest group of patients were RAEB-1 at 9 (14%) and RAEB-2 at 14 (22%) along with RCMD at 18 (28%) and 15 (23%) MDS-U, 2 (3%) MDS 5q, 4 (6%) RARS and 2 (3%) were considered atypical. Cytogenetic analysis was normal in 17 (26%) with 7 (11%) having trisomy 8, and 11 (16%) and 14 (22%) having abnormalities of chromosome 7 and 5, respectively. IPSS-R were very low, low, intermediate, high, and very high in 4%, 30%, 28%, 21% and 17%, respectively. Leukemic transformation (LT) occurred in 6 (9%). The 4 year overall survival and progression free survival was 35% and 34%, respectively. Median overall survival and progression free survival was 30.2 and 29.7 months, respectively. Nine out 65 h-MDS patients were treated with a HMA, azacitidine (4) or decitabine (5). The median age of patients was 71 years (range, 66-85) with 6 (66%) being males. The median cellularity of the diagnostic bone marrow was 15% with the majority of patients presenting with RAEB-1 (11%) and RAEB-2 (55%) classification and 2 (22%) cases of RCMD as well as 1 (11%) case of MDS with isolated 5q. Cytogenetic analysis was normal in 3 (33%). IPSS-R were low in 1 (11%), intermediate in 4 (44%), high in 1 (11%) and very high risk in 3 (33%). The median time to initiation of a HMA from diagnosis was 5 months with response assessed at a median of 4.2 months. Two patients had received prior therapy including lenalidomide (for MDS 5q) and one had 1 cycle of trial therapy. Two patients (22%) achieved a marrow complete remission at a median time of 2.95 months; with one case of relapse at 9.8 months using HMA. Three patients (33%) had LT at a median time of 7.9 months post initiation of HMA. Median overall survival of patients with LT was 20 days. A total of 4 (44%) patients remain alive with a leukemia free survival of 67% at 2 years. In comparing to h-MDS patients without HMA treatment versus HMA treated, median OS was 28.2 vs 50.9 months (p=0.41) and PFS was 28.1 vs 40.6 months (p=0.69), respectively. Conclusions: The results from our clinical experience confirm that hypocellular MDS is a rare variant and that it is distinct from normocellular/hypercellular MDS. Two thirds of h-MDS received HMA for the treatment of higher risk disease (RAEB1-2). HMA has some efficacy in h-MDS. Further studies are warranted to better understand the clinical significance and outcomes of hypocellular MDS. Disclosures Binder: American Society of Hematology: Research Funding. Al-Kali:Celgene: Research Funding.

scholarly journals Effect of Neoadjuvant Iodine-125 Brachytherapy Upon Resection of Glioma

2022 ◽  
Author(s):  
Congxiao Wang ◽  
Chao Liu ◽  
Han Jiang ◽  
Wei Zhang ◽  
Lili Yang ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Tumor Volume ◽  
Combined Therapy ◽  
Progression Free Survival ◽  
Neurological Injury ◽  
Large Tumor ◽  
Free Survival ◽  
Iodine 125 ◽  
Large Tumor Volume

Abstract Background: A more extensive surgical resection of glioma contributes to improved overall survival (OS) and progression-free survival (PFS). However, some of the patients lost the chance of surgical resection when the tumor involves critical structures. Purpose: The present study aimed to assess the feasibility of neoadjuvant 125I brachytherapy followed by total gross resection for initially inoperable glioma.Methods:Six patients diagnosed with inoperable glioma due to invasion of eloquent areas, bi-hemispheric diffusion, or large tumor volume received 125I brachytherapy. Surgical resection was performed when the tumor shrank, allowing a safe resection, assessed by the neurosurgeons. Patients were followed up after surgery.Results:Tumor shrinkage after adjuvant 125I brachytherapy enabled a total gross resection of all six patients. Four patients were still alive at the last follow-up, with the longest survival time of more than 50 months, two of which returned to a normal life with the KPS of 100. Another two patients got a neurological injury with the KPS of 80 and 50, respectively. One patient with grade Ⅱ glioma died 34 months, and another patient with grade Ⅳ glioma died 40 months later after the combined therapy.Conclusions: In the present study, the results demonstrated that 125I brachytherapy enabled a complete resection of patients with initially unresectable gliomas. 125I brachytherapy may offer a proper neoadjuvant therapy method for glioma.

scholarly journals Gamma Knife surgery for intracranial chordoma and chondrosarcoma: radiosurgical perspectives and treatment outcomes

2014 ◽  
Vol 121 (Suppl_2) ◽  
pp. 188-197 ◽  
Author(s):  
Ji Hee Kim ◽  
Hyun Ho Jung ◽  
Jong Hee Chang ◽  
Jin Woo Chang ◽  
Yong Gou Park ◽  
...  
Keyword(s):  
Overall Survival ◽  
Gamma Knife ◽  
Volume Change ◽  
Tumor Volume ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Rank Test ◽  
Tumor Control ◽  
Free Survival ◽  
Log Rank Test

ObjectIntracranial chordomas and chondrosarcomas are histologically low-grade, locally invasive tumors that are reported to be similar in terms of anatomical location, clinical presentation, and radiological findings but different in terms of behavior and outcomes. The purpose of this study was to investigate and compare clinical outcomes after Gamma Knife surgery (GKS) for the treatment of intracranial chordoma and chondrosarcoma.MethodsThe authors conducted a retrospective review of the results of radiosurgical treatment of intracranial chordomas and chondrosarcomas. They enrolled patients who had undergone GKS for intracranial chordoma or chondrosarcoma at the Yonsei Gamma Knife Center, Yonsei University College of Medicine, from October 2000 through June 2007. Analyses included only patients for whom the disease was pathologically diagnosed before GKS and for whom more than 5 years of follow-up data after GKS were available. Rates of progression-free survival and overall survival were analyzed and compared according to tumor pathology. Moreover, the association between tumor control and the margin radiation dose to the tumor was analyzed, and the rate of tumor volume change after GKS was quantified.ResultsA total of 10 patients were enrolled in this study. Of these, 5 patients underwent a total of 8 sessions of GKS for chordoma, and the other 5 patients underwent a total of 7 sessions of GKS for chondrosarcoma. The 2- and 5-year progression-free survival rates for patients in the chordoma group were 70% and 35%, respectively, and rates for patients in the chondrosarcoma group were 100% and 80%, respectively (log-rank test, p = 0.04). The 2- and 5-year overall survival rates after GKS for patients in the chordoma group were 87.5% and 72.9%, respectively, and rates for patients in the chondrosarcoma group were 100% and 100%, respectively (log-rank test, p = 0.03). The mean rates of tumor volume change 2 years after radiosurgery were 79.64% and 39.91% for chordoma and chondrosarcoma, respectively (p = 0.05). No tumor progression was observed when margin doses greater than 16 Gy for chordoma and 14 Gy for chondrosarcoma were prescribed.ConclusionsOutcomes after GKS were more favorable for patients with chondrosarcoma than for those with chordoma. The data also indicated that at 2 years after GKS, the rate of volume change is significantly higher for chordomas than for chondrosarcomas. The authors conclude that radiosurgery with a margin dose of more than 16 Gy for chordomas and more than 14 Gy for chondrosarcomas seems to enhance local tumor control with relatively few complications. Further studies are needed to determine the optimal dose of GKS for patients with intracranial chordoma or chondrosarcoma.

scholarly journals Double unrelated umbilical cord blood versus HLA-haploidentical bone marrow transplantation (BMT CTN 1101)

Blood ◽  
2020 ◽  
Author(s):  
Ephraim J Fuchs ◽  
Paul V. O'Donnell ◽  
Mary Eapen ◽  
Brent R Logan ◽  
Joseph H Antin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Mycophenolate Mofetil ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Progression Free Survival ◽  
Free Survival ◽  
Haploidentical Transplantation ◽  
Secondary Endpoints ◽  
Reduced Intensity

Results of two parallel phase II trials of transplantation of unrelated umbilical cord blood or bone marrow from HLA-haploidentical relatives provided equipoise for direct comparison of these donor sources. Between June 2012 and June 2018, 368 patients aged 18-70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were randomly assigned to undergo cord blood (n=186) or haploidentical (n=182) transplant. Reduced intensity conditioning comprised total body irradiation with cyclophosphamide and fludarabine for both donor types. Graft-versus-host disease prophylaxis for cord blood transplantation was cyclosporine and mycophenolate mofetil and for haploidentical transplantation, post-transplant cyclophosphamide, tacrolimus and mycophenolate mofetil. The primary endpoint was 2-year progression-free survival. Treatment groups had similar age, sex, self-reported ethnic origin, performance status, disease and disease status at randomization. Two-year progression-free survival was 35% (95% CI, 28-42%) compared to 41% (95% CI, 34-48%) after cord blood and haploidentical transplants, respectively (p=0.41). Pre-specified analysis of secondary endpoints recorded higher 2-year non-relapse mortality after cord blood, 18% (95% CI, 13-24%) compared to haploidentical transplantation, 11% (95% CI, 6-16%), p=0.04. This led to lower 2-year overall survival after cord blood compared to haploidentical transplantation, 46% (95% CI, 38-53) and 57% (95% CI 49-64%), respectively (p=0.04). The trial did not demonstrate a statistically significant difference in the primary endpoint, 2-year progression-free survival, between the donor sources. While both donor sources extend access to reduced intensity transplantation, analyses of secondary endpoints, including overall survival, favor haploidentical bone marrow donors. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute; ClinicalTrials.gov number, NCT01597778).

Prognostic impact of concordant and discordant cytomorphology of bone marrow involvement in patients with diffuse, large, B-cell lymphoma treated with R-CHOP

2013 ◽  
Vol 66 (5) ◽  
pp. 420-425 ◽  
Author(s):  
Hyoeun Shim ◽  
Jae-Il Oh ◽  
Sang Hyuk Park ◽  
Seongsoo Jang ◽  
Chan-Jeoung Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
International Prognostic Index Score ◽  
Large B Cell Lymphoma

BackgroundBone marrow involvement confers a poor prognosis in patients with diffuse, large, B-cell lymphoma (DLBCL). However, the prognostic significance of concordant and discordant bone marrow involvement in these cases differs. We analysed this further in patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) at a single institute.Design and MethodsThe cytomorphology of bone marrow involvement was evaluated in 632 patients who were diagnosed with DLBCL in primary tissues and had received R-CHOP therapy. Bone marrow trephine biopsies and clot sections were analysed, along with the immunohistochemical analysis of CD20, CD79a and CD3.ResultsBone marrow involvement was identified in 80 of our DLBCL patient subjects (12.7%). Of these, 32 (40%) showed discordant bone marrow involvement, and 48 (60%) showed concordant involvement. Kaplan–Meier survival analysis showed that progression-free survival and overall survival was poorer in the concordant group (p<0.001). Multivariate analysis, adjusted for the International Prognostic Index score, showed that concordant involvement was an independent predictor of progression-free survival (p<0.001) and overall survival (p=0.011). Discordant involvement was not a negative prognostic factor independent of the International Prognostic Index.ConclusionsPrognostication based on bone marrow involvement cytomorphology is a useful indicator of progression-free survival and overall survival, independent of the International Prognostic Index score, in DLBCL patients. Accurate staging based on morphology should thus be included in bone marrow examinations of such cases.

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