Analysis of Risk Factors and Outcome for Extramedullary Relapses Post Allogeneic Stem Cell Transplantation for Myeloma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4562-4562
Author(s):  
Myo Htut ◽  
Firoozeh Sahebi ◽  
George Somlo ◽  
Pablo Parker ◽  
Chatchada Karanes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Ratio ◽  
Allogeneic Stem Cell Transplantation ◽  
Novel Agents ◽  
Cell Transplant ◽  
Allogeneic Hsct

Abstract Abstract 4562 Analysis of Risk Factors and Outcome for Extramedullary Relapses post Allogeneic Stem Cell Transplantation for Myeloma Relapse after both autologous and allogeneic hematopietic stem cell transplant (HSCT) is common in multiple myeloma (MM). Unusual sites of relapse have been reported after allogeneic HSCT in the form of isolated extramedullary (EM) lesion or light chain escape. It is hypothesized that these EM relapses are due to changes in the marrow microenvironment or selection of resistant subclones from therapy with novel agents and or allogeneic stem cell transplantation. Several case reports have shown that EM relapse is associated with dismal prognosis compared to medullary or bone marrow (BM) relapse. To study the relapse patterns and outcome, we performed a retrospective analysis of 56 pts who underwent tandem autologous-nonmyeloablative allogeneic HSCT (auto-allo) or reduced intensity conditioning (RIC) allogeneic transplant. Between January, 2000 to March 2008, 38 pts received planned auto-allo HSCT using melphalan (200 mg/m2) prior to auto-HSCT and TBI (200 cGy) prior to allo-HSCT and 18 pts received RIC allo-HSCT following fludarabine (125mg/m2) and melphalan 140mg/m2. Donors included 52 HLA matched siblings and 4 matched unrelated donors.Table 1.Patients characteristicsParametersPts without relapse (n)BM relapse (n)EM relapse (n)P-valueTotal number of patients33167.Age at transplant (median, yr.)50.85154.10.84Interval between diagnosis-transplant (median, mo.)11.79.414.60.12B2-micr (median)2.06 (1.18-10)1.67 (1.28-2.15)2.08 (0.79- 9.05)0.15Median f/u for alive pts (yr.)6.88.79.6.Type of transplant....Auto- allo graft70% (23)69 % (11)57 % (4)0.84RIC30% (10)31% (5)43% (3)Response before allograft....CR/PR64% (21)56% (9)71% (5)0.79MR/SD/RE/refractory36% (12)44% (7)29% (2)Stage III disease at the time of transplant78% (25)81% (13)100% (7)0.94Ch 13 del at dx18% (6)12% (2)29% (2)0.69Novel agent prior to transplant45% (15)38% (6)57% (4)0.74 RESULTS After a median follow up of 7.8 years; there were 16 BM and 7 EM relapses. There was no correlation between either relapse or the pattern of relapse (BM and EM) and development of acute and chronic graft vs. chronic disease (GVHD). The risk ratio for BM relapse in 5 year is 0.27 for patients with chronic GVHD (cGVHD) and 0.15 for patients without cGVHD (P=0.69). The risk ratio for EM relapse in 5 year is 0.12 for patients with cGVHD and 0.25 for patients without cGVHD (P=0.10) (Figure 1). Overall survival (OS) and progression-free survival (PFS) for the whole group (N=56) is shown in figure 1. Four year OS was 43% in EM group and 88% in BM group (P=0.005) (Figure 3). There were no significant differences between age, B2 microglobulin, numbers of treatment before HSCT, use of novel agents before HSCT, cytogenetics, stage, transplant regimen and development of GVHD and pattern of relapse (BM vs. EM). In conclusion our data suggest that EM relapse can occur post allogeneic HSCT and is associated with shorter overall survival. The development of GVHD does not prevent against EM relapse. Disclosures: No relevant conflicts of interest to declare.

Depth of Response with Stem Cell Transplantation and Outcome for Multiple Myeloma in the Era of Novel Agents.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1228-1228
Author(s):  
David Dingli ◽  
Francesca Gay ◽  
Francis Buadi ◽  
Angela Dispenzieri ◽  
Suzanne R Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Novel Agents ◽  
Cell Transplant ◽  
Time To Progression ◽  
Depth Of Response ◽  
The Impact

Abstract Abstract 1228 Poster Board I-250 Background It is generally believed that a ‘deeper’ response in multiple myeloma is associated with an improved outcome, including time to progression (TTP) as well as overall survival. Before the advent of novel agents such as IMiDs or bortezomib, complete responses (CR) were rare in the absence of stem cell transplantation (ASCT). In that era, the depth of response achieved before ASCT tended to be dwarfed by the impact of the conditioning used for stem cell transplant. Hence, the time to progression in patients achieving CR before ASCT was not different from those who achieved CR after ASCT. With novel agents, CR rates are higher and again raises the question of whether patients who achieve CR before ASCT benefit from consolidation with ASCT. The purpose of this analysis was to determine whether CR achieved before ASCT still benefit when consolidated with ASCT Methods After approval from the Institutional Review Board at Mayo Clinic Rochester, the transplant dysproteinemia database was searched for all patients treated with novel agents and patients who achieved CR before or after ASCT were identified. In addition, we identified patients with IMiDs induction therapy and achieved CR but did not proceed with ASCT. Relevant demographic, clinical and laboratory characteristics were determined at the time of ASCT. Comparisons between groups were performed with non-parametric tests. Overall survival and TTP were determined from the time of ASCT using the Kaplan-Meier method. Results A total of 354 patients who underwent ASCT within a year from diagnosis of multiple myeloma were identified. Of these, 24 achieved CR before proceeding to ASCT while another 100 patients achieved CR after ASCT. There were no differences between the two cohorts with respect to age (58 vs 57.5 yr, p=0.14), gender, number of treatment regimens (1 vs 1, p=0.83), time to ASCT (6.5 vs 6.3 months, p=0.80), b2M (2.41 vs 2.26, p=0.58) and ISS (p=0.23). Patients who achieved CR before ASCT had a lower plasma cell burden (1.0 vs 5.0%, p<0.0001) and lower labeling index (0 vs 0, p=0.0007). Aneuploidy was present in none of the patients with CR before transplant compared to 10% in patients who achieved CR after ASCT (p=0.11). The median TTP for patients with CR before ASCT has not been reached (71% at 70 months) compared to 30 months for patients who achieved CR after ASCT (p=0.07). After a median follow up of 70 months, 21 of 24 patients (88%) with CR before transplant are alive compared to 76 of 100 patients with CR after ASCT (p=0.44). In contrast, for patients who achieved CR with IMiDs but did not proceed with ASCT, 55% have not progressed at 51 months and 71.7% are alive at 51 months (Gay et al ASH, 2009). Conclusion Our results suggest that patients who achieve CR before ASCT benefit from high-dose therapy and experience prolonged TTP without the need for maintenance therapy. ASCT after achieving CR can result in a deeper response with improvement in disease free and overall survival. Disclosures Lacy: celgene: Research Funding. Gertz:celgene: Honoraria; genzyme: Honoraria; millenium: Honoraria; amgen: Honoraria.

Risk Factors of GANCICLOVIR–RELATED Neutropenia After Allogeneic STEM CELL Transplantation: A Retrospective Monocenter Study On 547 Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4186-4186
Author(s):  
Geoffroy Venton ◽  
Roberto Crocchiolo ◽  
Jean El-Cheikh ◽  
Sabine Furst ◽  
Angela Granata ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cmv Reactivation ◽  
Related Mortality

Abstract Abstract 4186 Introduction: Cytomegalovirus (CMV) disease is a serious complication that may occur in the weeks or months following bone marrow transplantation. Therefore it must be treated as soon as positive CMV reactivation is noticed: pre-emptive therapy has demonstrated to improve survival among patients reactivating CMV after transplantation. However, GANCICLOVIR (GCV) as well as CMV infection itself involves a well-know marrow toxicity, notably neutropenia that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. So far, only two studies specifically identified risk factors and outcome of GCV –related neutropenia, finding low marrow cellularity between day 21 and 28, hyperbilirubinemia > 6mg/dl during the first 20 days, serum creatinine > 2mg/l after day 21, and absolute neutrophil count as predictive factors. However, transplantation has evolved in recent years, especially thanks to the reduce intensity conditioning (RIC) and supportive care. The present analysis aims at identifying risk factors of neutropenia among a large cohort of patients treated by pre-emptive GCV who received allogeneic stem cell transplantation at our Institution over last years. Patients and Methods: This is a retrospective study on a cohort of 547 consecutive patients allografted from January 2005 to June 2011 at our Institution. Diagnoses were: acute myeloid and lymphoblastic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, myeloproliferative and myelodisplasic syndromes, aplastic anemia, metastatic solid tumor. Transplants were performed using three sources: bone marrow, peripheral blood stem cells, cord blood; patients receiving haploidentical transplant were excluded. Donors were HLA-sibling and matched or mismatched unrelated ones. Myeloablative, non-myeloablative and RIC regiments were administered according to local guidelines or established protocols. The principal objective of the study was to identify factors associated with the occurrence of grade 3–4 neutropenia among patients receiving antiviral therapy due to CMV reactivation. Secondarily, overall survival (OS), transplant-related mortality (TRM) and relapse/progression were analyzed and compared between patients who reactivated CMV vs. those who did not. Results: A total of 547 patients were included in the analysis. One hundred ninety patients presented CMV reactivation (34.7%). Thirty patients were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally one hundred and sixty patients were analyzed. We found that ANC above 3000 is a protective factor, (HR= 0.26, CI 95 %, 0.125–0.545, p < 0001); creatinine <2ml/dl after 21 days is a risk factor for GCV- related neutropenia (HR= 2.4, CI 95%, 1.11 – 5.17, p = 0.002) as well as a high viral load (HR=2.68, CI 95%, 1.25–5.737, p = 0.01). Using landmark analysis at day +100, overall survival (OS) at five years is lower for patients with CMV reactivation 43% (32–54) vs. 57% (46–68), p<0.0001. As concerns treatment-related mortality (TRM), we found a higher TRM among patients who developed CMV reactivation: 29% (21–36) vs. 12% (8–17), p=0.003. There is no significant difference in the risk of relapse in patients who reactivated CMV vs. those who did not reactivate 32 % vs. 34 % (p=n.s.). In conclusion, this large analysis revealed three risk factors of GCV-related neutropenia among patients with CMV reactivation after allogeneic hematopoietic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, thus potentially reducing morbidity and mortality associated with CMV reactivation. Disclosures: No relevant conflicts of interest to declare.

Risk Factors For Readmission Following Allogeneic Hematopoietic Stem Cell Transplantation and Impact On Overall Survival

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 555-555
Author(s):  
Laura Spring ◽  
Shuli Li ◽  
Robert J. Soiffer ◽  
Joseph H. Antin ◽  
Edwin P. Alyea ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Significant Risk ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
The Impact

Abstract Background Recent initiatives to improve patient safety and reduce healthcare costs have focused on preventing hospital readmissions. Historically, patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) have high rates of hospital readmission. The purpose of this study was to identify the incidence and associated risk factors for readmissions in allogeneic HSCT patients and to evaluate the impact of readmissions on overall survival. Methods A retrospective review of patients receiving a myeloablative (MAC) or reduced intensity conditioning (RIC) HSCT at Dana Farber/Brigham and Women’s Hospital between January 1, 2005 and December 31, 2010 was performed. At our institution, RIC transplant patients are typically discharged on day +1. The 30-day readmission rate, a standard benchmark used by the Centers for Medicare & Medicaid Services, and the day 100, a traditional assessment point in transplantation, readmission rates were examined. Reasons for readmission as well as sociodemographic, disease, and HSCT-related variables were evaluated. Risk factors for readmission and the impact of readmission on overall survival were assessed by multivariate regression analysis. Results A total of 1097 HSCT patients were reviewed. In the MAC group, 130 of 495 (26.3%) patients were readmitted within 30 days of discharge and 194 (39.2%) patients were readmitted by day 100 following transplantation. 74.2% of the MAC patients had one readmission by day 100. In the RIC group, 105 of 602 (17.4%) patients were readmitted within 30 days of discharge and 185 (30.7%) patients were readmitted by day 100 following transplantation. 69% of the RIC patients had one readmission by day 100. In both groups, the most frequent reasons for readmission were infection (27.6% in MAC group, 26% in RIC group), fever without a source (19.1% in MAC group, 19% in RIC group), and graft versus host disease (17.9% in MAC group, 15.1% in RIC group). In the MAC group, a multivariate logistic regression model of the probability of being readmitted suggested that the principal risk factors for readmission by day 100 were infection during the index transplant admission (OR 1.9, p=0.0006) and Latino ethnicity (OR 4.6, p=0.013). In the RIC group, active disease at the time of HSCT (OR 2.1, p=0.0001), infection during the index admission (OR 4.8, p<0.0001), a mismatched donor (OR 2.1, p=0.030) and non-private (32.1% Medicaid, 66.4% Medicare, 1.5% other) insurance (OR 1.6, p=0.029) were significant risk factors for readmission by day 100. In a landmark analysis of patients who survived beyond the studied time points, the 5-year overall survival (OS) for those readmitted within 30 days of discharge from the index HSCT in the MAC group was 42% compared with 56% among patients not readmitted (p=0.0026). Similarly, OS in the RIC group was 26% compared with 50% (p<0.0001). The 5-year OS for those readmitted by day 100 following HSCT in the MAC group was 52% compared with 61% among patients not readmitted (p=0.058) and in the RIC group was 26% compared with 57% (p=<0.0001). After adjusting for age, donor type, and the disease risk index (DRI), a multivariate analysis confirmed that readmission within 30 days of discharge or by day 100 was associated with decreased OS (table 1). Conclusions Infection and fever without a source were the most common causes of readmission after HSCT. In the RIC group, disease, transplant, and sociodemographic factors were associated with readmission. Being readmitted within 30 days of discharge from transplant was a significant risk factor for a lower 5-year overall survival rate in both the RIC and MAC groups. A better understanding of the risk factors for readmission in the HSCT population will allow for more transitional care and clinical resources to be focused on the highest risk patients. Strategies to decrease readmissions may improve the overall survival of patients undergoing allogeneic HSCT. More research is needed to better learn how to balance early discharge with preventable readmissions. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Development of an integrated model of care for allogeneic stem cell transplantation facilitated by eHealth—the SMILe study

2021 ◽  
Author(s):  
Lynn Leppla ◽  
Anja Schmid ◽  
Sabine Valenta ◽  
Juliane Mielke ◽  
Sonja Beckmann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Practice ◽  
Stem Cell Transplantation ◽  
Computer Science ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Science Methods ◽  
Cell Transplant ◽  
Care Model ◽  
Transplant Team

Abstract Purpose Allogeneic stem cell transplantation would benefit from re-engineering care towards an integrated eHealth-facilitated care model. With this paper we aim to: (1) describe the development of an integrated care model (ICM) in allogeneic SteM-cell-transplantatIon faciLitated by eHealth (SMILe) by combining implementation, behavioral, and computer science methods (e.g., contextual analysis, Behavior Change Wheel, and user-centered design combined with agile software development); and (2) describe that model’s characteristics and its application in clinical practice. Methods The SMILe intervention’s development consisted of four steps, with implementation science methods informing each: (1) planning its set-up within a theoretical foundation; (2) using behavioral science methods to develop the content; (3) choosing and developing its delivery method (human/technology) using behavioral and computer science methods; and (4) describing its characteristics and application in clinical practice. Results The SMILe intervention is embedded within the eHealth enhanced Chronic Care Model, entailing four self-management intervention modules, targeting monitoring and follow-up of important medical and symptom-related parameters, infection prevention, medication adherence, and physical activity. Interventions are delivered partly face-to-face by a care coordinator embedded within the transplant team, and partly via the SMILeApp that connects patients to the transplant team, who can monitor and rapidly respond to any relevant changes within 1 year post-transplant. Conclusion This paper provides stepwise guidance on how implementation, behavioral, and computer science methods can be used to develop interventions aiming to improve care for stem cell transplant patients in real-world clinical settings. This new care model is currently being tested in a hybrid I effectiveness-implementation trial.

scholarly journals Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients

2001 ◽  
Vol 115 (3) ◽  
pp. 630-641 ◽  
Author(s):  
Sébastien Maury ◽  
Jean-Yves Mary ◽  
Claire Rabian ◽  
Michael Schwarzinger ◽  
Antoine Toubert ◽  
...  
Keyword(s):  
Risk Factors ◽  
Immune Deficiency ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Adult Patients

scholarly journals BK virus-associated hemorrhagıc cystitis in patients wıth allogeneıc hematopoıetıc cell transplantation: report of three cases

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Duygu Mert ◽  
Hikmetullah Batgi ◽  
Alparslan Merdin ◽  
Sabahat Çeken ◽  
Mehmet Sinan Dal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hemorrhagic Cystitis ◽  
Immunosuppressive Treatment ◽  
Active Agent ◽  
Bk Virus ◽  
Cell Transplant ◽  
Hematopoietic Stem

BK virus is a human polyoma virus. It is acquired in early childhood and remains life-long latent in the genitourinary system. BK virus replication is more common in receiving immunosuppressive therapy receiving patients and transplant patients. BK virus could cause hemorrhagic cystitis in patients with allogeneic stem cell transplantation. Hemorrhagic cystitis is a serious complication of hematopoietic stem cell transplantation. Hemorrhagic cystitis could cause morbidity and long stay in the hospital. Diagnosis is more frequently determined by the presence of BK virus DNA detected with quantitative or real-time PCR testing in serum or plasma and less often in urine. The reduction of immunosuppression is effective in the treatment of BK virus infection. There are also several agents with anti-BK virus activity. Cidofovir is an active agent against a variety of DNA viruses including poliomyoma viruses and it is a cytosine nucleotide analogue. Intravenous immunoglobulin IgG (IVIG) also includes antibodies against BK and JC (John Cunningham) viruses. Hereby, we report three cases of hemorrhagic cystitis. Hemorrhagic cystitis developed in all these three cases of allogeneic stem cell transplantation due to acute myeloid leukemia (AML). BK virus were detected as the cause of hemorrhagic cystitis in these patients. Irrigation of the bladder was performed. Then levofloxacin 1×750 mg intravenous and IVIG 0.5 gr/kg were started. But the hematuria did not decreased. In the first case, treatment with leflunomide was started, but patient died due to refractory AML and severe graft-versus-host disease after 4th day of leflunamide and levofloxacin treatments. Cidofovir treatment and the reduction of immunosuppressive treatment decreased the BK virus load and resulted symptomatic improvement in the second case. Initiation of cidofovir was planned in the third case. Administration of cidofovir together with the reduction of immunosuppression in the treatment of hemorrhagic cystitis associated with BK virus in allogeneic stem cell transplant recipients could be a good option.

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