Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1578-1582 ◽  
Author(s):  
Martha Wadleigh ◽  
Paul G. Richardson ◽  
David Zahrieh ◽  
Stephanie J. Lee ◽  
Corey Cutler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Short Interval ◽  
Significant Risk ◽  
Disease Status ◽  
Significant Risk Factor ◽  
Gemtuzumab Ozogamicin ◽  
Myelogenous Leukemia ◽  
Increased Risk ◽  
Acute Myelogenous ◽  
Previously Treated

AbstractGemtuzumab ozogamicin (GO), a monoclonal antibody used in the treatment of acute myelogenous leukemia (AML) has been linked to the development of venoocclusive disease (VOD). We conducted a retrospective study of 62 patients with previously treated AML/MDS (myelodysplastic syndrome) who underwent allogeneic stem cell (SC) transplantation at our institution from December 2000 to October 2002 to determine whether GO exposure prior to allogeneic SC transplantation increases the risk of developing VOD. Fourteen patients received GO prior to SC transplantation. Of 62 patients, 13 (21%) developed VOD; 9 (64%) of 14 with prior GO exposure developed VOD compared with 4 (8%) of 48 without prior GO exposure (P < .0001). Logistic regression controlling for sex, disease status, donor type, and graft-versus-host disease prophylaxis identified prior treatment with GO as a significant risk factor for VOD (odds ratio [OR], 21.6; 95% confidence interval [CI], 4.2-112.2]. Nine of 10 patients who underwent SC transplantation 3.5 months or less following GO developed VOD compared with none of 4 patients who underwent SC transplantation more than 3.5 months from GO administration. Three of 14 patients who received GO prior to SC transplantation died of VOD. We conclude that patients undergoing SC transplantation within a short interval from GO administration are at increased risk of developing VOD.

Analysis of Factors Influencing Skin Toxicity after Autologous Hematopoeitic Stem Cell Transplant.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2882-2882
Author(s):  
Anuj Mahindra ◽  
Brian Bolwell ◽  
Ronald Sobecks ◽  
Lisa Rybicki ◽  
Stacey Brown ◽  
...  
Keyword(s):  
Stem Cell ◽  
Statistical Significance ◽  
Autologous Transplantation ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Skin Toxicity ◽  
Significant Risk Factor ◽  
Cell Transplant ◽  
Increased Risk ◽  
Preparative Regimen

Abstract Skin toxicity is a known but understudied complication of autologous stem cell transplantation (ASCT). Its assessment is complicated by the development of graft-vs-host disease following allogeneic transplantation. We chose therefore to study skin toxicity following autologous transplantation. We retrospectively reviewed the records of 392 patients undergoing ASCT to analyze risk factors for skin toxicity, its association with mucositis and its effect on survival. Skin toxicity was assessed three times a week during the transplant admission and was classified as none, mild, moderate, severe or life threatening. The most severe skin toxicity is used in this analysis. Mucositis was assessed using the modified oral mucositis assessment scale (OMAS). Median patient age was 53 years; 63% of patients had non-Hodgkin s lymphoma (NHL), 17.6% multiple myeloma, 13.5% Hodgkin disease (HD) and 5.9% acute leukemia. Peripheral blood progenitor cells were mobilized with G-CSF alone (36%) or the combination of etoposide plus G-CSF (64%). The preparative regimen was busulfan (Bu)/cyclophosphamide (Cy) /etoposide in 82% and Bu/Cy alone in 18%. Two hundred and sixty patients (67%) developed skin toxicity of which 143 patients (36.5%) had mild, 105 (26.8%) had moderate and 16 (3.9%) had severe skin toxicity. Factors associated with the development of any skin toxicity in univariable analysis were male gender (p=0.028), diagnosis of NHL (p<0.001) or HD (p=0.001), higher number of prior chemotherapy regimens (p<0.001), mobilization regimen containing etoposide (p< 0.001) and ASCT preparative regimen containing etoposide (p<0.001). Moderate skin toxicity correlated with the above as well. Only the inclusion of etoposide in the mobilization regimen was associated with an increased risk of severe skin toxicity (p=0.035). Etoposide in the preparative regimen remained the most significant risk factor for the development of skin toxicity in multivariable analysis. Higher OMAS score was associated with increased severity of skin toxicity (p<0.001) as shown in the boxplot below: Patients with severe skin toxicity appeared to have worse overall survival (p=0.054) and relapse-free survival (p=0.08), but these findings did not reach statistical significance. Conclusion: A substantial proportion of patients develop skin toxicity following autotransplantation. The inclusion of etoposide in the preparative regimen is associated with a significant increased frequency in multivariable analysis. The severity of skin toxicity correlates closely with the severity of mucositis. Figure Figure

Prior Treatment with Chemotherapy Associated to Gemtuzumab Ozogamicin (GO) Does Not Increase the Risk of Veno-Occlusive Disease (VOD) after Allogeneic Stem Cell Transplantation (all-SCT).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1121-1121
Author(s):  
Patrice Chevallier ◽  
Thomas Prebet ◽  
Pascal Turlure ◽  
Mathilde Hunault ◽  
Stephane Vigouroux ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Toxicity ◽  
Chronic Gvhd ◽  
Short Interval ◽  
Gemtuzumab Ozogamicin ◽  
Prior History ◽  
High Risk Population ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Increased Risk

Abstract The combination of chemotherapy and GO is increasingly used for the treatment of CD33+ AML patients either at diagnosis or at time of relapse. GO is classically known to induce liver toxicity, that may significantly increase the risk of VOD, especially in patients receiving allo-SCT. A single study by Wadleigh et al (Blood, 2003) suggested an increased risk of VOD in patients who underwent myeloablative HSCT within a short interval from GO administration (&lt;3.5 m.). However, no large series have comprehensively assessed this risk thus far. Here, we analysed the outcome of a cohort of 44 HSCT patients who had received previous combination of chemotherapy + GO in the course of their disease. This retrospective study included 44 patients (males, n=21) who received allo-SCT between Dec. 2001 and June 2008 after prior exposure to GO. Median age was 50 (range:3–67). There were 41 CD33+ AML, 2 CD33+ ALL and 1 CD33+ myeloid sarcoma. Before allo-SCT, 37 patients received the MIDAM regimen (GO: 9 mg/m², n=36; or GO 4.5 mg/m², n=1 at day 4 + Ara-C 1g/m²/12 hours day 1–5 + Mitoxantrone 12 mg/m²/day day 1–3). In 3 patients receiving MIDAM, Mitoxantrone was omitted. GO 9 mg/m² + other combinations of chemotherapy were used in the remaining 4 patients. Indications for the GO-based chemotherapy were as follow: first induction, n=3; second induction, n=4; primary refractory disease, n=14; first relapse, n=19; second relapse, n= 4. Only 1 patient developed VOD after receiving GO. In this series, 5 patients received an additional course of consolidation with GO+chemotherapy. Of note, 15 patients (34%) received prior auto-SCT. Median interval between last administration of GO and allo-SCT was 4.2 (range, 0.8–26.3) months, with 19 patients allografted &lt;3.5 months from GO administration. At time of allo-SCT, 33 patients were in CR, and 11 remained refractory. The majority of patients (n=36; 82%) received a reduced intensity conditioning (RIC) regimen prior to allo-SCT, while 8 patients received a myeloablative regimen. The stem cell source was PBSC in 26, cord blood in 15, bone marrow in 2 and a CD34+ selected PBSC in 1 patient. Eleven patients received an allograft from an HLA matched related donor (MRD), 1 from an HLA mis-MRD, 16 from an HLA matched unrelated donor (MUD), and 1 from an HLA mis-MUD. All patients (but one who received defibrotide because of a prior history of VOD) received low-dose heparin as VOD prophylaxis. Engraftment was observed in 34 patients (77%) at a median of 15 (range, 8–43) days after allo-SCT. With a median FU of 15 (range, 1.1–63) m. for surviving patients, OS and DFS after allo-SCT were 45% (95%CI, 30–61%) and 38% (95%CI, 24–54%) at 3 years respectively. At time of analysis, 22 patients were still alive, while 22 patients died. The causes of death included: disease progression in 13, 1 fungal infection, 2 acute GVHD, 1 chronic GVHD, 3 multi organ failures, 1 ARDS, and one case of VOD, for an overall incidence of TRM of 20% in this high risk population. The incidence of Grade ¾ hyper-bilirubinemia was 13.5% (n=6), with this being 21% in patients with a short (&lt;3.5 m.) GO-allograft interval (n=4/19) vs. 8% in all others (P=NS). In all, the incidence of VOD was 7% (n=3), with this being 10.5% (n=2/19) in patients with a short GO-allograft interval (&lt;3.5 m.) vs. 4% (n=1/25) for all others (P=NS). Also, a myeloablative regimen was not associated with an increased risk of VOD (12.5%, n=1/8 vs RIC 5.5%, n=2/36, P=NS). Overall, these encouraging results suggest that GO-based (mostly salvage) therapy in combination with chemotherapy prior to allo-SCT is feasible and does not result in an excessive rate of toxicity, especially VOD, after allo-SCT.

Outcomes of Myeloablative Hematopoietic Stem Cell Transplantation for Patients with Acute Myelogenous Leukemia with Relapsed or Refractory Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2366-2366
Author(s):  
Courtney D. DiNardo ◽  
Alison Loren ◽  
Steven Goldstein ◽  
Stephen J. Schuster ◽  
Alexander Perl ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Acute Myelogenous Leukemia ◽  
Disease Status ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Acute Myelogenous ◽  
Disease Free

Abstract Abstract 2366 Background: Allogeneic hematopoietic stem cell transplant (HSCT) has been shown to be of some benefit for patients with acute myelogenous leukemia (AML) with untreated early relapse. However, outcomes for patients who have morphologic evidence of relapsed leukemia are not well defined. We describe our experience with HSCT for patients with active AML at the time of transplant, to determine prognostic factors for outcome after transplant. Patients and Methods: We analyzed recipients of myeloablative HSCT from 1997 to 2009 at our institution with morphologically active AML at the time of transplant. Patients were identified through our transplant database, and disease status was verified through medical record review. Forty patients were included based on the presence of circulating blasts at the time of admission for transplant, and/or a positive bone marrow biopsy (>5% bone marrow blasts) immediately prior to transplant. There were 6 patients coded as “relapsed/refractory” in our database whose disease status at the time of transplant was unable to be confirmed and thus were excluded from analysis. Results: Baseline patient and transplant characteristics are shown in Table 1. 30% of patients were transplanted for primary induction failure, 22% for first untreated relapse (no treatment between first documented relapse and HSCT), 35% for first refractory relapse (did not attain CR with treatment administered at time of first relapse), and 13% had second or greater refractory relapse. The overall survival for all patients was 82% at 30 days; 55% at 100 days; 28% at one year; and 18% at two years post-HSCT. Of 31 deaths, 71% were attributable to disease, 19% to regimen-related toxicity and infection, and 10% to graft-versus-host-disease (GVHD). Seven patients remain alive at the time of analysis, with 6 patients (15%) alive and free of disease more than 3 years post-HSCT. The median follow-up of the disease-free survivors is 9 years; Table 1 shows characteristics for this subgroup. We identified several patterns of interest. Four disease-free survivors were transplanted in first untreated relapse, yielding 44% (4/9 patients) with first untreated relapse that are long-term disease-free survivors. In addition, while most patients were transplanted with circulating blasts, 5 of 6 disease-free survivors did not have circulating disease. Although 40% of transplants were from unrelated donors, 5 of 6 disease-free survivors received sibling transplants. Conclusions: Our review of patients with morphologically apparent relapsed or refractory AML confirmed that a subset of patients can achieve a durable remission from HSCT. The majority of these long-term survivors shared important characteristics, including (1) lack of circulating blasts at transplant, (2) sibling donors, and (3) first untreated relapse disease status. This information may serve a prognostic purpose, and may assist in identifying appropriate candidates for transplant or for alternative therapies. However, it was not possible based on our analysis to predict reliably those who would not experience long-term survival. Except for second or greater refractory relapse, there was no factor that identified patients who had no benefit from HSCT. As such, HSCT remains a viable option with the potential for long-term disease-free survival in this population. Disclosures: No relevant conflicts of interest to declare.

Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies.

1994 ◽  
Vol 12 (12) ◽  
pp. 2527-2534 ◽  
Author(s):  
D L Darrington ◽  
J M Vose ◽  
J R Anderson ◽  
P J Bierman ◽  
M R Bishop ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Lymphoid Malignancies ◽  
Increased Risk ◽  
Acute Myelogenous ◽  
The Impact

PURPOSE To analyze the risk of developing myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) following autologous bone marrow transplantation (ABMT) or peripheral stem-cell transplantation (PSCT) and to determine the impact on failure-free survival (FFS). PATIENTS AND METHODS Patients underwent ABMT or PSCT for the treatment of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the University of Nebraska Medical Center. For those patients who went on to develop MDS/AML, controls were selected and a case-control-within-a-cohort study undertaken. RESULTS Twelve patients developed MDS or AML a median of 44 months following ABMT/PSCT. The cumulative incidence (P = .42) and the conditional probability (P = .32) of MDS/AML were not statistically different between HD and NHL patients. Age greater than 40 years at the time of transplant (P = .05) and receipt of a total-body irradiation (TBI)-containing regimen (P = .06) were predictive for developing MDS/AML in patients with NHL. CONCLUSION There is an increased risk of MDS/AML following ABMT/PSCT for lymphoid malignancies. NHL patients age > or = 40 years at the time of transplant and who received TBI are at greatest risk.

Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Cun-Xian Jia ◽  
Lin-Lin Wang ◽  
Ai-Qiang Xu ◽  
Ai-Ying Dai ◽  
Ping Qin
Keyword(s):  
Risk Factor ◽  
Family Income ◽  
Rural China ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Health Condition ◽  
Physical Illness ◽  
Rural Residents ◽  
Increased Risk ◽  
Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

Marrow irradiation with high-dose 153Samarium-EDTMP followed by chemotherapy and hematopoietic stem cell infusion for acute myelogenous leukemia

2006 ◽  
Vol 47 (8) ◽  
pp. 1583-1592 ◽  
Author(s):  
Vilmarie Rodriguez ◽  
Peter M. Anderson ◽  
Mark R. Litzow ◽  
Linda Erlandson ◽  
Barbara A. Trotz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Acute Myelogenous
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