Impact of preexisting CNS involvement on the outcome of bone marrow transplantation in adult hematologic malignancies.

1996 ◽  
Vol 14 (11) ◽  
pp. 3036-3042 ◽  
Author(s):  
K van Besien ◽  
D Przepiorka ◽  
R Mehra ◽  
S Giralt ◽  
I Khouri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Hematologic Malignancies ◽  
Control Group ◽  
High Dose ◽  
Cns Involvement ◽  
Cns Disease ◽  
History Of ◽  
The Impact

PURPOSE To determine the impact of prior or current CNS disease on the outcome of high-dose chemotherapy for patients with hematologic malignancies. PATIENTS AND METHODS In a 54-month period, 373 patients with hematologic malignancies underwent allogeneic or autologous bone marrow transplantation (BMT) or blood stem-cell transplantation using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen. Four patients with active CNS disease at BMT and 20 patients with a history of prior CNS disease were identified. The outcomes of those with a history of CNS disease were compared with those of a matched control group. RESULTS Of four patients with active CNS disease at the time of BMT, two had CNS recurrences and one recurred in the bone marrow. One patient died of treatment-related toxicity. Four of 20 patients with prior CNS involvement currently remain free of disease. At 2 years, the disease-free survival (DFS) rate was 23% +/- 19%, and the DFS rate for the control group 39% +/- 24% (P = .053). An increased rate of treatment-related toxicity and especially grades II to IV CNS toxicity accounted for the poorer outcome of patients who had a history of CNS disease. Recurrence rates were not significantly different between the two groups. Prior radiation to the CNS correlated with CNS complications posttransplant (p = .01). CONCLUSION Consolidation with TBC and BMT can induce prolonged DFS in a proportion of patients with a history of CNS disease. Such patients are at increased risk for CNS complications that lead to an inferior overall outcome when compared with a control group.

Unexpected 5 Year Survival Benefit in Patients Given Oral Cryotherapy During Conditioning for Stem Cell Transplantation. A Prospective Randomized Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4559-4559
Author(s):  
Anncarin Svanberg ◽  
Kerstin Öhrn ◽  
Gunnar Birgegard
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Marrow Transplantation ◽  
High Dose Chemotherapy ◽  
Control Group ◽  
High Dose ◽  
Oral Cryotherapy

Abstract Abstract 4559 Patients receiving high dose chemotherapy (HDC) in connection with bone marrow transplantation (BMT) often are afflicted with severe oral mucositis (OM). OM may affect 75–99% of patients. Oral cryotherapy has been shown to alleviate symptoms of mucositis alleviating oral pain and inability to maintain nutritional status. In a randomised controlled trial we have shown that patients receiving oral cryotherapy had less mucositis, less use of i.v. opioides and fewer doses of total parenteral nutrition (TPN) than a control group receiving routine oral care. Adult patients scheduled for bone marrow transplantation were randomly assigned to experimental (EXP) or control (CTR) group. A stratified randomisation was used with regard to type of transplantation (autologous vs allogeneic/unrelated donor (URD)). Randomisation was performed between January 2002 and August 2004. The final sample consisted of 78 patients, (31 autologous BMT and 8 allogeneic/URD BMT), and 39 constituted the CTR group and received standard treatment (31 autologous BMT and allogeneic/URD BMT). Concern has been raised for a possible protection of tumor cells by cryotherapy which could increase the risk of relapse and reduce survival. Thee aim of the present study was to investigate any difference in survival and relapse rates 5 years post-BMT for the two treatment groups from the randomised study. After 5 years, 25/39 (64%) of the cryotherapy patients were alive compare to 15/39 (38%) of the control group (odds ratio 0,35, 95 % CI 0,14–0,88, p = 0,025)(Figure 1). No significant difference could be found with regard to the relapse rate between the groups. Most of the deaths were due to relapse. The study offers no support for the speculation about tumor protection from cryotherapy during high dose chemotherapy conditioning for stem cell transplantation. These data indicate that oral cryotherapy is a safe prophylactic treatment for mucositis during chemotherapy. Unexpectedly, the cryotherapy group showed a significantly better 5-year survival. Further analyses are needed to explore the difference in survival rate. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies [published erratum appears in Blood 1987 Jun;69(6):1789]

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1015-1020 ◽  
Author(s):  
KG Blume ◽  
SJ Forman ◽  
MR O'Donnell ◽  
JH Doroshow ◽  
RA Krance ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Acute Leukemia ◽  
Total Body Irradiation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
High Dose ◽  
Pharmacokinetic Studies ◽  
Total Body

In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16–213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.

A Sequence Variation in the Promoter Region of PTPN22 Gene Predicts Relapse After HLA-Fully-Matched Unrelated Bone Marrow Transplantation for Hematologic Malignancies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3088-3088
Author(s):  
Luis J. Espinoza ◽  
Akiyoshi Takami ◽  
Katsuya Nakata ◽  
Makoto Onizuka ◽  
Yasuo Morishima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Promoter Region ◽  
Conflicts Of Interest ◽  
Hematologic Malignancies ◽  
Negative Regulator ◽  
Ptpn22 Gene ◽  
Transplant Outcomes ◽  
The Impact

Abstract Abstract 3088 The protein tyrosine phosphatase non-receptor 22 (PTPN22), also known as LYP, is an intracellular phosphatase ubiquitously expressed with particularly high expression in hematopoietic tissues that is a critical negative regulator of signaling through the T cell receptor and has emerged as the strongest common genetic risk factor for human autoimmunity outside the major histocompatibility complex. In this study we analyzed the impact of the polymorphism rs2488457 (1123G>C) in the promoter region of PTPN22 gene on transplant outcomes in patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The PTPN22 rs2488457 genotypes were retrospectively analyzed in a cohort of 663 patients with hematologic malignancies and their unrelated donors. The presence of the C/C or C/G genotype in the donor side was associated with a significantly lower incidence of relapse compared to the donor G/G genotype (28% vs. 34% 5-years, P =0.05) (Fig.1). No difference was noted in transplant-related mortality, or graft-versus-host disease in relation to the rs2488457 polymorphism. The donor C/C or C/G genotype remained statistically significant for relapse in the multivariate analyses (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.43 to 0.85; P =0.004). These differences in relapse did not significantly affect on overall survival (OS) (48% vs. 49% 5-years, P =0.85). The recipient PTPN22 genotypes did not significantly influence the transplant outcomes. These results suggest an association of the donor C/C or C/G genotype with lower disease relapse. These could therefore be useful in selecting the donor and creating therapeutic strategies for improving the final outcome of allogeneic BMT. Disclosures: No relevant conflicts of interest to declare.

Significant Impact of IL-17A Gene Polymorphism On Transplant Outcomes After HLA-Fully-Matched Unrelated Bone Marrow Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2305-2305
Author(s):  
Akiyoshi Takami ◽  
J. Luis Espinoza ◽  
Makoto Onizuka ◽  
Takakazu Kawase ◽  
Takamasa Katagiri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Chemokine Production ◽  
Transplant Outcomes ◽  
The Impact ◽  
Standard Risk

Abstract Abstract 2305 Poster Board II-282 IL-17 plays an active role in autoimmune diseases and organ transplant rejection through its mediating proinflammatory responses and inducing inflammatory cytokine and chemokine production. This study examined the impact of donor and recipient polymorphism in the IL-17A gene on the clinical outcomes in unrelated HLA-fully-matched myeloablative bone marrow transplantation (BMT) through the Japan Marrow Donor Program. The IL-17A polymorphism (rs2275913, G197A) was retrospectively analyzed in a total 145 recipients with hematologic malignancies and their unrelated donors. In patients with standard risk disease, the donor IL-17A-197A genotype was associated with significantly improved OS (adjusted HR, 0.32; 95% CI, 0.13-0.79; p=0.01) and reduced transplant related mortality (TRM) (adjusted HR, 0.27; 95% CI, 0.11-0.67; p=0.005), but no impact on disease relapse or the development of grades II-IV acute GVHD or chronic GVHD. Patients with standard risk disease receiving transplants from donors with the 197A genotype had better 5-year OS (71% vs. 40%, p=0.02; Figure) and lower 5-year TRM rate (27% vs. 60%, p=0.02). The IL-17A polymorphism did not significantly influence the transplant outcomes in patients with high risk disease. These results suggest transplantation from IL-17A-197A positive donor is advantageous in improving OS and reducing TRM after HLA-matched unrelated BMT for standard risk hematologic malignancies. Disclosures: No relevant conflicts of interest to declare.

A Minor Genetic Variation In the Granzyme B Gene Predicts Relapse After HLA-Fully-Matched Unrelated Bone Marrow Transplantation for Hematologic Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 681-681
Author(s):  
Luis J. Espinoza ◽  
Akiyoshi Takami ◽  
Kayoko Yamada ◽  
Mayu Yamada ◽  
Yuki Motohashi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Conflicts Of Interest ◽  
Granzyme B ◽  
Hematologic Malignancies ◽  
Effector Cells ◽  
Transplant Outcomes ◽  
A Minor ◽  
The Impact

Abstract Abstract 681 Granzyme B (GZMB) is a serine protease with important roles mediating target-cell apoptosis induced by natural killer cells and cytotoxic CD8+ T cells. The polymorphism rs8192917 (A55G) in the GZMB gene has been reportedly associated with the ability of effector cells to secrete GZMB. In this study we analyzed the impact of GZMB polymorphism on transplant outcomes in patients undergoing unrelated HLA-fully-matched myeloablative bone marrow transplantation (BMT) through the Japan Marrow Donation Program. The GZMB genotypes were retrospectively analyzed in a cohort of 360 pairs of patients with hematologic malignancies and their unrelated donors. The presence of the G/G genotype in the donor side was associated with a significantly higher incidence of relapse (62% vs. 32%, P=0.04; Fig 1). Multivariate analysis revealed that the donor G/G genotype, which is expected to produce lower levels of GZMB after stimulation, (Girnita et al, Transplantation 2009) was an independent risk factor for relapse (hazard ratio, 4.17; 95% confidence interval, 1.63 to 10.70; P=0.003). The host GZMB genotypes did not significantly influence the transplant outcomes. These results suggest an association of low GZMB secretors with disease relapse. These could therefore be useful in selecting the donor and creating therapeutic strategies for improving the final outcome of allogeneic BMT. Disclosures: No relevant conflicts of interest to declare.

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