Late Onset Eosinophilia (beyond Day 100), Rather Than Early Onset Eosinophilia, Has a Significant Prognostic Impact on Transplant Outcomes after Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1062-1062
Author(s):  
Dong Hwan (Dennis) Kim ◽  
Gizelle Popradi ◽  
John Kuruvilla ◽  
Vikas Gupta ◽  
Mark Minden ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Early Onset ◽  
Late Onset ◽  
Prognostic Impact ◽  
Allogeneic Pbsct ◽  
Univariate Analyses

Background: The significance of eosinophilia after allogeneic stem cell transplantation (SCT) is presently unknown. The eosinophil activation pathway involves Th2 cytokines and thus eosinophilia after PBSCT may reflect Th2 pathway activation. Previous data suggest that blood eosinophilia precedes or coincides with the development of acute or chronic graft-verus-host disease (aGVHD or cGVHD). In a recent report, Aisa et al reported that patients with peripheral eosinophilia within 100 days post-SCT had a superior overall survival (OS) and transplant-related mortality (TRM) along with a lower incidence of cGVHD compared to those who did not (Transplant Int 2007). Methods: A retrospective analysis of 237 recipients who received allogeneic PBSC from related donors at PMH was performed (myeloablative:reduced intensity conditioning 162:75). The present study evaluated the impact of early (before day 100: EEo) or late onset (beyond day 100: LEo) eosinophilia (≥0.5x109/L in peripheral blood) on transplant outcomes after allogeneic PBSCT. The patient population included 237 recipients of allogeneic PBSC from related donors (male:female 137:100, median age 51 years-old). Results: Biphasic pattern of eosinophilia with 2 peaks before day 100 and beyond day 100 was observed after PBSCT. The cumulative incidence of early onset eosinophilia was 43% at day 100. EEo was not associated with the development of grade 3–4 aGVHD (p=0.1), but there was a trend in the development of grade 2–4 aGVHD (p=0.053). In univariate analyses, the group with EEo showed favorable OS (p=0.002), TRM (p=0.05) and a lower relapse incidence (p=0.05) compared to those without EEo but did not have improved GVHD-specific survival (GSS). EEo did not predict the grade of aGVHD or response to steroid therapy for aGVHD. EEo was significantly associated with the development of late onset eosinophilia (p=0.000004 by chi-square test, p=0.00007 by McNemar test). The cumulative incidence of LEo was 62% at 2 years with median onset of 1 year after SCT. There was an association with the onset of cutaneous (p=0.001), oral (p=0.04), ocular (p=0.02) or pulmonary cGVHD (p=0.03). In univariate analyses, with median follow-up durations of 773 days (patients with LEo) and 679 days (patients without LEo), significant differences were observed in favor of those with LEo in terms of 3 year OS (86% vs 41%, p=0.00000000005), TRM at 3 years (10% vs 37%, p=0.000003), 3 year relapse rate (11% vs 31%, p=0.00003) and 3-year GSS (90% vs 64%, p=0.00001). In multivariate analyses, the LEo, rather than EEo, was identified as a significant favorable prognostic factor for OS (p=0.000006, hazard ratio [HR] 0.21), TRM (p=0.0006, HR 0.24), relapse incidence (p=0.003, HR 0.28) and GSS (p=0.001, HR 0.26). Conclusion: The late onset eosinophilia (beyond day 100), not EEo, seemed to have an important prognostic implication for outcome after allogeneic PBSCT. Further studies are warranted to validate its prognostic impact on SCT outcomes. Figure 1. Comparisonof overall survival (A) and GVHD-specific survival (B) between patients with and without late onset eosinophilia after allogeneic PBSCT Figure 1. Comparisonof overall survival (A) and GVHD-specific survival (B) between patients with and without late onset eosinophilia after allogeneic PBSCT

Comparative Analysis of Outcomes of Allogeneic Peripheral Blood Stem Cell Transplantation From Related and Unrelated Donors.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3381-3381
Author(s):  
Byung Woog Kang ◽  
Shi Nae Kim ◽  
Joon Ho Moon ◽  
Joo-Seop Jung ◽  
Goon-Jae Cho ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Peripheral Blood Stem Cell ◽  
Chronic Gvhd ◽  
P Value ◽  
Cmv Infection ◽  
Blood Stem Cell Transplantation

Abstract Abstract 3381 Poster Board III-269 This study compared the results of allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated and related donors, and involved 235 consecutive patients from 10 centers who received an allogeneic PBSCT for hematological malignancies between Jan 2004 and Dec 2008. Among these patients, 160 (68.1%) received an HLA-matched related PBSCT and 75 (31.9%) a matched unrelated PBSCT. Sixty-five patients (27.7%) had a high-risk disease status at transplantation. The cumulative incidence of acute graft-versus-host disease (GVHD) was 43.9% for the related PBSCT group and 59.3% for the unrelated PBSCT group (P-value:0.011). Although the cumulative incidence of chronic GVHD was no different between the related (54.2%) and unrelated (64.9%; P-value:0.199) PBSCT groups, the cumulative incidence of extensive chronic GVHD was higher among the unrelated PBSCT group (34.9%) than among the related PBSCT group (17.0%; P-value:0.015). Plus, the unrelated PBSCT group showed a higher cumulative incidence of CMV infection (44.6%) than the related PBSCT group (26.8%; P-value:0.002). The overall survival rate at four-year was 58.2% versus 49.1% (p=0.698) and the cumulative incidence of relapse 28.4% versus 25.0% (P-value:0.289) for the related and unrelated PBSCT groups, respectively. Among the factors examined, unrelated PBSCT (P-value:0.024), the CD34-positive cell count (>6 × 106/kg; P-value:0.041), and CMV infection (P-value:0.066) were all related with a higher incidence of extensive chronic GVHD. However, in a multivariate analysis, only unrelated PBSCT was identified as a risk factor for the development of extensive chronic GVHD (hazard ratio=2.012, 95% confidence interval=1.006-4.023; P-value:0.048). In conclusion, the overall survival and relapse incidence were not significantly different between the related and unrelated PBSCT groups. However, a higher incidence of CMV infection and extensive chronic GVHD was observed in the unrelated PBSCT group. Disclosures: No relevant conflicts of interest to declare.

Multidrug Resistance-1 Gene Polymorphism Associated with the Outcomes after Allogeneic HLA-Identical Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1757-1757
Author(s):  
Dong Hwan Kim ◽  
Seok Bong Jeon ◽  
Jin Ho Baek ◽  
Nan Young Lee ◽  
Jong Gwang Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Multidrug Resistance ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Mdr1 Gene ◽  
Solid Organ ◽  
Blood Concentrations

Abstract Background: The pharmacokinetic impact of multidrug resistance-1 (MDR1) gene single nucleotide polymorphisms (SNPs) has been already investigated in solid organ transplantation field, however, data is still lacking in an allogeneic stem cell transplantation (SCT) setting. Methods: A total of 82 patients receiving an allogeneic HLA-identical sibling (n=70) or unrelated SCT (n=12) with graft-versus-host disease (GVHD) prophylaxis of cyclosporine-A (CSA) plus methotrexate (MTX) were included in the current study. Two SNPs of MDR1 gene (C3435T and G2677T/A) were analyzed using PCR/RFLP assay. Results: As regards G2677T/A SNP, GG genotype showed a higher incidence of NRM compared to non-GG genotype (67% vs. 32%, p=0.0073), yet not C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival (OS) was significantly correlated with G2677T/A genotype (p=0.0048), yet not with C3435T (p=0.5041) or MDR1 haplotype (p=0.4086). However, no difference in the relapse incidence was noted according to G2677T/A, C3435T genotype or MDR1 haplotype. In a multivariate analysis, those patients without GG genotype at G2677T/A were found to have favorable prognosis in terms of OS (p=0.003) or NRM (p=0.031) along with occurrence of chronic GVHD (p<0.001 for OS, p=0.001 for NRM), standard disease risk (p=0.045 for OS) or acute grade 0,1 GVHD (p=0.019 for NRM). However, no correlation was found between the blood concentrations of CSA and MDR1 genotype and CSA neurotoxicity and MDR1 genotype. Conclusion: The G2677T/A genotype seemed to be associated with the transplantation outcomes, especially NRM. Further study is warranted to clarify its mechanism of MDR1 SNPs other than pharmacokinetic aspects. Figure. Overall survival (A) and cumulative incidence of non-relapse mortality (B) according to G2677T/A MDR1 genotype Figure. Overall survival (A) and cumulative incidence of non-relapse mortality (B) according to G2677T/A MDR1 genotype

Prognostic Impact of the Detection of the WT1 Gene mRNA with Peripheral Blood in Adult Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3289-3289
Author(s):  
Shuichi Miyawaki ◽  
Nahoko Hatsumi ◽  
Toshiharu Tamaki ◽  
Tomoki Naoe ◽  
Keiya Ozawa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Consolidation Therapy

Abstract Background: Approximately 70–80% of all newly diagnosed patients with adult AML achieve a complete remission (CR). However, only about one third of those pts remain free of disease for more than 5 years. It is therefore important to predict which pts are most likely to suffer a relapse and thus perform alternative treatments such as stem cell transplantation in order to improve the prognosis of AML. We evaluated the impact of the detection of Wilms’ tumor gene1 (WT1) mRNA in the peripheral blood on the prognosis of AML pts. Patients and Methods: From June 1, 2001 to October 30, 2003 a study was performed on 191 pts with AML which evaluated the clinical usefulness of a WT1 mRNA assay kit for the early detection of relapse in AML pts (submitted in Rinsho Ketsueki). From these 191 pts, we selected the subjects for this study. All selected subjects achieved a complete remission, and also had their WT1 expression analyzed after consolidation therapy. The pts were excluded if they had received a stem cell transplantation before relapse. The WT1 mRNA levels were determined using the WT1 mRNA assay kit (Otsuka Pharmaceutical Co. Ltd) in accordance with the standard operating procedures using peripheral blood. The lower limit of detection was 50 copy/μgRNA. Therefore, less than 50 copy/μgRNA was judged as negative. All induction, consolidation and maintenance therapies were performed according to institutional standards. Results: Of 118 pts who achieved a complete remission, 50 pts (median age: 56 yrs 22–86) were evaluable. Their median WT1 mRNA levels before induction therapy was 48327 copy/μgRNA (137–329185). The WT1 mRNA levels at diagnosis did not correlate with either the relapse rate, DFS or OS, respectively. After CR, the WT1 mRNA level ranged from <50 copy/μg to 30732 copy/μgRNA. Thirty-four (69.4%) pts were positive and 15 pts (30.6%) were negative for the WT1 mRNA. The relapse rate of the positive pts and of the negative pts was 73.5% and 40.0% (P=0.0248 sensitivity=80.6 % specificity=50.0%), respectively. The OS rate at 3 years was 53.1% in the positive pts and 79.0% in the negative pts (P=0.1227), respectively. The DFS rate at 3 years was 30.0% in the positive pts and 60.0 % in the negative pts (P=0.0906), respectively. After consolidation therapy, the WT1 mRNA level ranged from <50 copy/μgRNA to 49174 copy/μgRNA. The WT1 positive pts numbered only 15 pts (32.6%) and the negative pts numbered 31 (67.4%). The relapse rate of the positive pts and the negative pts was 80.0% and 54.8% (P=0.0974), respectively. The OS of rate at 3 years was 42.8% in the positive pts and 69.8% in the negative pts (P=0.0381), respectively. The DFS rate at 3 years was 20.0% in the positive pts and 50.0% in the negative pts (P=0.0116). The rate of relapse within 1 year was 73.3% in the positive pts and only 33.3% in the negative pts (P= 0.0116). Conclusion: This study shows that the detection of the WT1 mRNA in the peripheral blood after treatment closely correlated with the prognosis in AML.

Monitoring of Donor Chimerism in CD34+ Peripheral Blood Progenitors Allows to Detect Minimal Residual Disease after Allogeneic Stem Cell Transplantation -Results of a Randomized Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 340-340
Author(s):  
Martin Bornhaeuser ◽  
Uta Oelschlaegel ◽  
Gesine Bug ◽  
Uwe Platzbecker ◽  
Karin Lutterbeck ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Preemptive Therapy ◽  
Study Group ◽  
Minimal Residual

Abstract Relapse of hematological malignancy remains a major complication after allogeneic stem cell transplantation. This is especially true for patients receiving minimal or reduced-intensity conditioning therapy. Analysis of donor chimerism (DC) is an important diagnostic tool to assess the risk of relapse after allogeneic stem cell transplantation, especially in patients lacking a specific marker suitable for monitoring of minimal residual disease. The sensitivity of a standard PCR assay amplifying short-tandem-repeat sequences can be improved significantly by investigating sorted CD34+ peripheral blood cells. We prospectively compared the serial analysis of DC in selected CD34+ cells and unmanipulated whole blood (WB) within a randomised study in 131 patients with CD34+ hematological malignancies (AML, ALL and MDS) surviving more than 100 days after transplantation. The primary end-point was the association between decreasing CD34+ DC and haematological relapse. Whenever a decreasing CD34+ or WB DC was confirmed and no signs of active GvHD were present, a rapid taper of CsA or tracolimus (50% every 5–7 days) was suggested. If no GvHD occurred within 14 days after the stop of CsA or tacolimus, patients were scheduled to receive donor lymphocyte infusions (DLI) in incremental doses. The cumulative incidence of relapse was significantly increased in patients with decreasing or incomplete CD34+ DC (62% vs. 38%, p=0.01). This was associated with a lower probability of overall survival (20% vs. 39%, p=0.03). The interval between the decrease in CD34+ DC and hematological relapse was 35 days (range 0–567) in the study group compared to only 8 days (range 0–63) in the control group monitored by WB DC analysis (p=0.05). The median time between a decrease in CD34+ DC and WB DC was 14 days (range, 0 to 445). Patients receiving preemptive therapy triggered by decreasing CD34+ DC had a significantly higher probability of disease-free survival compared to cases monitored and treated according to WB DC (19% vs. 0%, p=0.009). Multivariate analysis revealed age, disease-risk and decreasing CD34+ DC as independent risk-factors for overall survival in the study group. In summary, we could demonstrate that the quantification of DC in CD34+ selected cells is a sensitive method to predict relapse and survival after allogeneic SCT. Although this technology opens a window for preemptive therapy, new treatment approaches have to be employed to improve the overall outcome of patients with recurrence of residual disease after allogeneic stem cell transplantation.

Evaluation of NIH Consensus Criteria for Classification of Late Acute and Chronic Gvhd in Reduce Intensity Conditioning (RIC) Stem Cell Transplantation (SCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1139-1139 ◽  
Author(s):  
Jifang Zhou ◽  
Sylvain Thepot ◽  
Aurrore Perrot ◽  
Marie Robin ◽  
Regis Peffault de Latour ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Time Dependent ◽  
Increased Risk ◽  
Nih Consensus Criteria

Abstract Abstract 1139 Poster Board I-161 Background Chronic graft-versus-host disease (GVHD) occurs frequently after allogeneic stem cell transplantation (SCT) and has an impact on morbidity and survival. The National Institutes of Heath (NIH) consensus criteria for the diagnosis of GVHD, emphasized clinical manifestations of GVHD rather than the classical time of onset (day 100). Incidence and impact in term of relapse and no-relapse mortality (NRM) of this new classification is not well known after RIC. Methods We retrospectively reviewed 116 consecutive patients (pts) in Saint Louis' Hospital undergoing an SCT for hematologic malignancy and surviving at least day + 100 after RIC between August 2005 and December 2008. We evaluated non-relapse mortality (NRM) and recurrent malignancy. Cumulative incidence was computed using death as a competing event. Incidence of relapse and NRM was counted from 100 days post-transplant for patients without chronic GVHD or from chronic GVHD onset. Patients with relapse/progression before chronic GVHD onset were considered as not having chronic GVHD in these analyses. The association of occurrence of chronic GVHD with the risk of relapse and non-relapse death was analyzed using time-dependent covariates in cause-specific proportional hazards models. Results Among 116 pts ( M/F: 71/45), with a median age of 53 years old (19-68 years) 28 pts (24%) were transplanted for acute leukemia in, 11 pts (9%) for chronic leukemia, 27 pts (23%) for lymphoma, 30 pts (26%) for MPD/MDS and 20 pts (17%) for plasma cell disorder. Sixty-three pts (54%) received HLA-identical sibling transplantation, 53 pts (46%) received transplantation from unrelated donors. Source of stem cells was mobilized peripheral blood stem cell for 108 pts (93%), bone marrow for 4 pts (3%) and 4 cord blood (3%). After a median follow-up of 18 months (range 5-45 months), a total of 67 pts (58%) developed chronic GVHD according to the Seattle day 100 landmark criteria and when using NIH consensus criteria, 55 pts (47%) developed chronic GVHD, including 43 pts (53%) with classic chronic GVHD and 8 pts (10%) overlap syndrome. Patients reclassified included; 3 pts with late onset acute GvHD, 19 pts had recurrent and 8 had persistent acute GVHD (numbers do not to previous sentence because some of these patients latter developed chronic GvHD). The cumulative incidence of chronic GVHD at 36 months was 64% (95%CI; 53%-73%) when using Seattle criteria compared to 56% (95%CI; 45%-67%) with NIH chronic GVHD criteria. Two-year Cumulative incidences of relapse and NRM using both classifications are summarized in Table. In Cox model with GvHD as a time dependent covariate, the NRM was significantly higher in patients with late onset, persistent and recurrent acute GVHD compared to no GVHD (hazard ratio (HR) 31, 47 and 30; p = 0.005, p <0.0001, p <0.0001, respectively), whereas the NRM was statistically increased in case of chronic GVHD using Seattle day 100 criteria (HR: 2.8; P=0.034). Conclusion The cumulative incidence of chronic GVHD “decrease” about 10% when using NIH consensus criteria compared to Seattle criteria in our cohort of RIC. Most of the NRM occurred beyond 100 days after SCT was due to the increased risk of NRM in patients with late onset, recurrent or persistent acute GVHD. Disclosures No relevant conflicts of interest to declare.

Cytomegalovirus Infection and Lymphopenia Are Associated with Increased Mortality Post Autologous Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4208-4208
Author(s):  
Alessandro de Moura Almeida ◽  
Erika Maria Macedo ◽  
Claudia Mac Donald Bley ◽  
Fabio R. Kerbauy ◽  
Paulo Vidal Campregher ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
Univariate Analysis ◽  
Hodgkin's Lymphoma ◽  
Prognostic Impact ◽  
Cmv Infection

Abstract Abstract 4208 Introduction: Despite preventive and therapeutic antiviral medication cytomegalovirus (CMV) infection is still a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (SCT). Only limited data on CMV infection and disease are available in autologous SCT recipients. Previous studies have demonstrated that the probability of CMV infection is nearly 60% in seropositive patients and 23% in seronegative patients undergoing autologous SCT, but its impact in mortality is unclear. Methods: We retrospectively reviewed the medical records of 101 patients undergoing autologous SCT at Hospital Israelita Albert Einstein from January, 2005 to July, 2012. CMV infection was defined as a quantitative real time PCR assay showing greater than 165 copies and/or positive CMV pp65 antigenemia assay. Lymphocyte count was registered at 15th day after SCT and lymphopenia was defined as an absolute lymphocytes count (ALC) < 500 at that time point. Overall survival (OS) was estimated from the time of transplant until death, with surviving patients censored at last follow-up. Variables entered into the multivariate Cox analysis were those with a p-value <0.10 in the univariate analysis. CMV infection was analyzed as a time-dependent covariate, considering the time to CMV infection. Statistical analysis was performed with STATA (v11.0) and alfa error was defined as 5%. Results: The majority of patients were male (62.4%) and the median age was 58 years old (range: 3–76). Peripheral stem cell harvest was the main source of cells (92%). A positive serological CMV status was found in 93.75% of patients. Most common indications for autologous SCT were multiple myeloma (34%), non-Hodgkin's lymphoma (40%) and Hodgkin's lymphoma (6%). After a median follow-up of 2 years, the OS for the whole cohort was 61% (95% confidence interval [CI] 48–72%). CMV infection post SCT was seen in 26% of patients. In the univariate analysis, development of CMV infection and presence of D15 lymphopenia were associated with a higher mortality (CMV infection-hazard ratio [HR] 3.32 [95%IC 1.61–6.84]; p= 0.001; D15 lymphopenia- HR 2.37 [95% IC 1.11–5.05]; p= 0.024). Patients who developed CMV infection in the setting of D15 lymphopenia had the worse outcome (2-years OS 19%; 95% CI 9–43%; figure 1). D15 lymphopenia was not associated with a higher rates of CMV infection (p=0.41). In Cox multivariate analysis, lower overall survival was demonstrated in female patients (HR= 2.23, 95%IC 1.08–4.58; p= 0.029), in the presence of D15 lymphopenia (HR= 2.56, 95%IC 1.19–5.51; p= 0.016) and CMV infection (HR: 3.33, 95% IC1.61–46.86; p= 0.001). Conclusion: CMV infection post-autologous SCT is associated with a decreased survival, and in the concomitant presence of D15 lymphopenia appears to indicate a subgroup of patients with very poor outcome. It is possible that CMV infection does not lead directly to increased mortality, but is rather a surrogate marker of decreased immune function post-ASCT. Future studies should prospectively evaluate the incidence and prognostic impact of CMV infection post-ASCT and correlate with markers of immune recovery. Disclosures: No relevant conflicts of interest to declare.

Myelomatous Pleural Effusion of Multiple Myeloma: Characteristics and Outcome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3874-3874 ◽  
Author(s):  
Hyo Jung Kim ◽  
Dae Ro Choi ◽  
Gak-Won Yun ◽  
Eunkyung Park ◽  
Seok Jin Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Pleural Effusion ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Early Onset ◽  
Late Onset ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Onset Group

Abstract Abstract 3874 Poster Board III-810 Introduction Myelomatous pleural effusion (MPE) in multiple myeloma (MM) is rare (<1%). As most reported MPEs are in the form of case reports, the characteristics of MPE are unclear. We report 30 MM patients presenting with MPE, including 11 cases as the first clinical manifestation of MM. To the best of our knowledge, this is the largest retrospective study ever reported about MPE. Patients and Methods Multicenter retrospective data of MM patients presenting MPE, who were diagnosed from January 1998 to June 2009 were analyzed. Diagnosis of MPE was based on positive cytology or biopsy in conjunction with M protein by protein electrophoresis or immunofixation in pleural effusion. Results The median age was 53 (range 21-78). Twenty patients were male and 10 were female. The myeloma isotype was IgG in 8, IgA in 7, IgD in 5, light chain in 9 and non-secretory myeloma in 1 patient. Most patients had high-risk disease based on initial D-S stage IIIA or IIIB (83%). Thirteen of 19 patients, who had available BM chromosomal analysis or FISH result, showed various karyotypic abnormalities including deletion of chromosome-13 (n=8). MPE was the first manifestation of MM in 11 patients (early-onset group). In the other 19 patients (late-onset group), MPE developed at a median of 20 months (range 1 – 75) from diagnosis of MM. The effusions were left-sided in 6, right-sided in 9 and bilateral in 15 patients. In more than half of the cases, a thoracic skeletal lesion, lung parenchymal lesion, pleural involvement or mediastinal lymphadenopathy was concomitantly present. Before the development of MPE, median 2 lines of chemotherapy (range 1 – 9) were applied in late-onset group. Seven patients of this group received high-dose chemotherapy with stem cell transplantation (6 autologous and 1 allogeneic stem cell). After onset of MPE, the median number of chemo-regimen was 1 (range 0 -3) in both groups and 3 patients got high-dose chemotherapy with autologous stem cell transplantation (1 in early-onset and 2 in late-onset group). After onset of MPE, total 27 chemo-regimens were applied to 19 patients and the regimens were based on VAD (vincristine, adriamycin, dexamethasone) in 12, thalidomide in 5, bortezomib in 4 and other regimen in 6. Pleurodesis was done in 2 patients. MPE disappeared in 11 patients and median response duration, defined as days from disappearance to relapse of MPE or death of any cause, was 123 days (95% confidence interval (CI): 10 – 236). Median survival was 66 days (95% CI: 29 – 103) from onset of MPE and 16 months (95% CI: 5 – 28) from initial diagnosis of MM. From onset of MPE, median survival was 84 (95% CI: 57 – 111) and 55 days (95% CI: 0 – 113, p=1.0) in early and late-onset group, respectively. From initial diagnosis of MM, median overall survival was 2.8 (95% CI: 2.4 – 3.2) and 26 months (95% CI: 12 – 40, p<0.001) in early and late-onset group, respectively. Causes of death were progression of disease, progression with concomitant infection or infection (50, 23 and 8 %, respectively). Conclusions Base on this analysis, MPE is a poor prognostic indicator, irrespective of the time of onset. When pleural effusions develop in a patient with MM, clinicians should perform prompt and appropriate diagnostic work-up. In the case of MPE, aggressive treatment including novel agents or autologous stem cell transplantation should be considered, especially if MPE is the initially presenting manifestation of MM. Further evaluation of the utility of various novel chemotherapeutic agents in the setting of MPE is needed to improve treatment outcome. Disclosures: No relevant conflicts of interest to declare.

Low Counts Of Natural Killer Cells CD56 bright CD16 negative After Engraftment Are Associated With Worse Survival In Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4625-4625
Author(s):  
Matheus Vescovi Gonçalves ◽  
Mihoko Yamamoto ◽  
Eliza Y. S. Kimura ◽  
Vergilio Antonio Renzi Colturato ◽  
Maura Valerio Ikoma ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Natural Killer Cells ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Related Mortality

Background Natural Killer Cells are innate immune system cells important in host defenses against viruses and tumor cells. Two subpopulations are well described: NK CD56bright CD16neg (NK56++16-, lower frequency on peripheral blood-PB, high cytokine production) and NK56dim16pos (NK56+16+, higher frequency on PB, high cytotoxic activity). They are activated through a balance between signals given from activating and inhibitory receptors (KAR and KIR, respectively). The ligands of KIRs are the MHC molecules and in the absence of compatible MHC, NK cells are activated. In the allogeneic hematopoietic stem cell transplantation (HSCT), recent studies showed that NK cells recovery is important on infection control and, in the presence of a KIR-MHC mismatch, they may be important on graft versus host disease (GVHD) and graft versus leukemia effects. However few studies evaluated NK subpopulations recovery and HSCT endpoints. Objectives To evaluate the impact of NK subpopulations recovery on HSCT endpoints: relapse, GVHD, non-relapse mortality and overall survival. Patients and Methods NK (CD3-, CD56+) subpopulations (NK56++16- and NK56+16+) were quantified by multiparametric flow cytometry at 9 sequential time points (before conditioning, at engraftment, and at days 3, 7, 14, 21, 60, 100 and 180 after engraftment). Overall, 111 patients, from 4 HSCT centers (65% male, median age 17 years, range 1-74), receiving bone marrow (BM, 46%), umbilical cord (UCB, 32%) or peripheral blood (PB, 22%) from unrelated (n=90) or related donors (n=21) were studied. The most common diagnosis was acute leukemia (AML 36%, ALL 31%, MDS 9%, CML 9%, Aplastic anemia 8%). Most patients received myeloablative conditioning (MAC) regimens (60%). Antithymocyte globulin (ATG) was used in 44 patients (40%) and total body irradiation (TBI) in 56 (51%). Median follow up time was 14 months (range 4-35). Results Eighty-six patients presented sustained allogeneic recovery (no differences among sources). Of these, median time to neutrophil engraftment was 18 days (range: 8-52). The cumulative incidence (CI) of non-relapse-related mortality (NRM) was significantly higher in those with lower counts of NK56++16– during first 3 weeks after HSCT (34% at 1 year for patients with less than 30 cells/uL at day 21 vs 11% for patients with higher counts, p=0.03). Overall survival was significantly worse in patients with lower counts of NK56++16- subpopulations in the day 21 after engraftment (86% at 1 year vs 54% for patients with less than 30 cells/uL – p=0.003). CI of grade II-IV acute GVHD and relapse were not significantly affected by NK counts. The number of NK56+16+ cells did not affect any endpoint studied. Cell source, age and conditioning regimen did not affect any of the NK subpopulations counts. In multivariate analysis, NK56++16- counts lower than 30 cells/uL at 21 and 60 days after engraftment remain an independent risk factor for non relapse mortality [HR: 4.8, CI (95%): 1.2-18.8]. Conclusions Low NK56++16- counts in the first weeks after HSCT are associated with increased non relapse related mortality, but not acute GVHD or relapse. The mechanisms that rules the NK56++16- role on immunity deserve further investigations. Disclosures: No relevant conflicts of interest to declare.

Donor KIR B Haplotype Is Associated with a Increased Rate of Leukemia Relapse and Worse Overall Survival after HLA Match Sibling Pediatric Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5926-5926
Author(s):  
Antonio Pérez-Martínez ◽  
Isabel Martinez ◽  
Jaime Valentin ◽  
Lucia Fernandez ◽  
Vicario José Luis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Nk Cell ◽  
Univariate Analysis ◽  
Blood Stem Cell ◽  
Leukemia Relapse

Abstract Introduction Graft versus leukemia (GvL) effect after hemotopoietic stem cell transplantation (HSCT) is mediated by donor immune cells recovery. Natural Killer (NK) cell alloreactivity is controlled by the interaction of activatory receptors and inhibitory killer-immunoglobulin-like receptors (KIRs) with major histocompatibility locus class I antigens on the leukemia cells. Haploidentical setting is a plattform for NK cell alloreactivity however HLA identical setting remains unclear. Methods and Patients We performed KIR-genotyping of HLA-identical sibling donors in 35 pediatric CD34 selection peripheral blood stem cell transplantations to identify genetic factors affecting leukemia relapse and overall survival. Univariate analysis of leukemia relapse and KIR genotyping was performed in order to identify independent variables predictive of outocome for pediatric acute lymphoblastic leukemia (ALL), (n=20) and acute myeloblastic leukemia (AML), (n=15). Results Donor B haplotype was observed in 21 cases (60%). Statistical analysis shown that donor B haplotype was associated with significantly more relapse in leukemia pediatric patients (38% vs. 0%) and worse overall survival (40% vs. 7%). Further analysis revealed that 2DL5a, 2DS3 and 2DS5 were associated with an increased rate of leukemia relapse (47% vs. 6%, 54% vs. 10% and 58% vs. 13%, respectively) and 2DL5a, 2DS1 and 3DS1 were associated with a worse overall survival (48% vs. 6%, 64% vs. 10% and 58% vs. 13%, respectively). No difference was observed in patients KIR haplotype or donor-recipient KIR haplotype mismatch. Conclusion In our study, which included only reduced intensity conditioning without antithymocyte globulin followed by related peripheral blood stem cell transplantation, we found a significant worse impact of donor KIR B haplotype in stem cell transplantation outcome. Our results suggest that donor KIR B haplotype (2DL5a, 2DS3 and 2DS5) increases leukemia relapse and also donor KIR B haplotype (2DL5a, 2DS1 and 3DS1) confer significant survival damage to HLA-identical sibling HSCT. Figure 1. Donor KIR genotyping (2DL5A, 2DS1 and 3DS1) impacts in overall survival. Figure 1. Donor KIR genotyping (2DL5A, 2DS1 and 3DS1) impacts in overall survival. Disclosures No relevant conflicts of interest to declare.

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