Outcome and Prognostic Factors for Patients Who Relapse After Allogeneic Stem Cell Transplantation.

Abstract Abstract 3069 Disease relapse remains a major obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with hematologic malignancies (HM), and the principal cause of failure after reduced intensity conditioning HSCT. Much work has focused on identifying the risk factors for relapse and devising strategies for its prevention, but comparatively little is known about the outcome of patients who relapse and the relevant prognostic factors in this setting. We conducted a retrospective study of 1080 consecutive adult patients with HM transplanted at our institution between 2004 and 2008. 351 (33%) relapsed at a median of 4.5 months after HSCT. The 4-year post-relapse overall survival (pr-OS) was 15%, with a median post-relapse follow-up of 39 months. Significant risk factors for post-relapse mortality included shorter time to relapse, higher disease risk index1 at HSCT, myeloablative conditioning, and high HCT-CI2 at HSCT. While being on immunosuppression at the time of relapse did not significantly affect outcome in multivariable models, a history of acute or chronic graft-versus host disease (GVHD) prior to relapse conferred a higher risk for death after relapse. Based on those 5 factors and their hazard ratio for mortality in the Cox models, we constructed a simple risk score that stratified patients into 4 groups, with 4-year pr-OS ranging from 64% in patients with fewer than 3 points (13% of the cohort, among whom over one third had myeloid diseases) to 0% in those with greater than 6 points (p<0.0001) (Figure). This score performed similarly in a historical validation cohort of 276 relapsed patients who were transplanted between 1998 and 2003. An analysis of the impact of post-relapse treatment on outcome showed that immune manipulation, through either donor lymphocyte infusion or repeat HSCT, was associated with significantly better pr-OS (4-year pr-OS 28% versus 9%, p<0.0001). Even though this likely reflects in part selection bias, the difference remained significant in models that accounted for other post-relapse prognostic factors, in landmark analyses of patients who survived at least 2 months from relapse, and in patients with active GVHD at the time of relapse. The results of this study may aid with prognostication and management of patients who relapse after HSCT, as well as motivate the design of clinical trials aimed at relapse prevention or treatment in the higher-risk groups. Figure. Post-Relapse Overall Survival by risk score. Figure. Post-Relapse Overall Survival by risk score. Risk factors are: Disease Risk Index (0 points for low risk, 1 point for intermediate, 2 points for high or very high)1Time to relapse (0 points for >24 months, 1 point for 6–24 months, 2 points for 3–6 months, 3 points for <3 months)HCT-CI (0 points for index of 0–2, 1 point for index of 3+)2Myeloablative conditioning (1 point)Prior GVHD (1 point) Disclosures: No relevant conflicts of interest to declare.

Download Full-text

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

Blood ◽

10.1182/blood.v122.21.555.555 ◽

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.

Download Full-text

Overall Outcome of Relapsed Acute Lymphoblastic Leukemia Can Be Improved by Stem Cell Transplantation and Early Treatment in Stage of Molecular Relapse

Blood ◽

10.1182/blood.v118.21.250.250 ◽

2011 ◽

Vol 118 (21) ◽

pp. 250-250

Author(s):

Nicola Goekbuget ◽

Daniel Stanze ◽

Renate Arnold ◽

Monika Brueggemann ◽

Rainer Fietkau ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Prognostic Factors ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Salvage Therapy ◽

Late Relapse ◽

Cns Involvement ◽

Early Relapse ◽

Remission Duration

Abstract Abstract 250 Survival of adult ALL has improved over the past decade to >50% with contemporary, risk adapted, targeted treatment strategies. However, published results of relapsed ALL are poor. In 4 retrospective studies with 1494 patients (pts) the CR rate after first salvage therapy was 40% and the long-term survival was only 6% including stem cell transplantation (SCT) (Thomas et al 1999, Tavernier et al 2007, Fielding et al 2007, Oriol et al, 2010). 1638 patients with newly diagnosed ALL were included in studies 06/99 and 07/03 of the German Multicenter Study Group for Adult ALL (GMALL). 547 patients with first hematologic relapse (HemRel) were evaluable for a retrospective analysis (378 chemotherapy, 169 post SCT). Median age was 33 (15–55) yrs. 432 pts had early (< 18 mo of 1st remission duration) and 115 late relapse. Salvage therapy was given according to physicians' choice and results are available in part of the pts. The aim was to achieve a CR and to perform SCT. Molecular relapse (MolRel) defined by standard criteria (Brüggemann et al, Leukemia, 2010) as reappearance of minimal residual disease (MRD) above 10-4 after prior molecular CR and measured by quantitative PCR of individual IgH/TCR rearrangements was detected in 43 pts. Response to salvage was evaluable in 224 pts with Ph-neg ALL with bone marrow (BM) relapse (no CNS involvement) during/after chemotherapy. The CR rate after first salvage was 42% and significantly inferior in early vs late relapse (36% vs 58%; p=.003). In early relapse the most frequently used regimens were FLAG-IDA (N=38; 42% CR) or a combination of HDAC/HDMTX/VP16/VCR/DEXA (N=38; 29% CR) in B-lineage and CLAEG (N=16; 19% CR) in T-lineage. In late relapses most frequently induction was repeated (N=30; 90% CR). In pts with failure after 1st salvage (N=82) the CR-rate after 2nd salvage was 33%. In relapse after SCT (N=48) the CR rate after 1st salvage was 23%. Median overall survival after relapse was 8.4 months and survival at 5 yrs 24%. Survival was significantly inferior in relapse post-SCT versus relapse on chemotherapy (15% vs 28%; p<.0001) and in BM±other vs CNS±other vs isolated extramedullary relapse (23% vs 27% vs 47%; p=.02). Prognostic factors for survival were analysed in 291 pts with Ph-neg ALL and BM relapse (no CNS involvement) on chemotherapy. Survival was superior in late vs early relapse (43% vs 22%; p<.0001), in pts aged 15–25 yrs vs 26–45 yrs vs 46–55 yrs (38% vs 28% vs 12%; p<.0001) and in pts with CR compared to failure/PR after 1st salvage (47% vs 13%; p<.0001). 75% of evaluable pts received SCT in any stage after relapse. Their survival at 5 yrs was 38% vs 0% without SCT (p<.0001). Survival was significantly better if SCT was performed in CR after 1st salvage vs later CR vs no CR (56% vs 39% vs 20%;p<.0001). Of pts with MolRel (N=43) 26% remained untreated, 19% received specific salvage therapy and in 55% first-line treatment was continued without modification. 11% (N=5) remained in CCR, 30% (N=13) underwent SCT in 1st CR and 58% (N=25) developed HemRel. Median remission duration without SCT in CR1 was 92 d until HemRel and no pt was in continuous CR after 3.5 yrs. Survival after 5 yrs was significantly superior in pts with SCT in CR1 (N=13; 100%) compared to those without (N=30; 24%) (p=.0006). Overall survival after 5 yrs was significantly superior after MolRel (45%) compared to HemRel (22%) (p=.003). Survival of pts with relapse during/after chemotherapy was 28% in the GMALL trials and superior compared to published data. Outcome after relapse was not uniformly poor but depended on prognostic factors such as age and time to relapse. The most important prognostic factor, however, was response to first salvage therapy, being very poor in early relapse. These pts suffer from chemorefractory disease and are candidates for experimental, targeted approaches. Improved overall outcome was mainly an effect of a high rate of SCT (75%) which was possible due to stringent donor search (related/unrelated) at diagnosis of relapse. Survival was significantly better if SCT was performed in CR. For the first time it could be demonstrated that outcome after molecular relapse is superior to outcome after hematologic relapse and this result underlines the relevance of MRD follow-up testing. Further improvement should therefore be achievable by early detection of molecular relapse, stratified relapse treatment, experimental approaches in early relapse and rapid transplant realisation with optimised procedures. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Autologous Stem Cell Transplantation in Patients with Autonomic Neuropathy Due to AL Amyloidosis

Blood ◽

10.1182/blood.v112.11.3318.3318 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3318-3318

Author(s):

David Dingli ◽

Shaji K. Kumar ◽

Francis K. Buadi ◽

Angela Dispenzieri ◽

Suzanne R. Hayman ◽

...

Keyword(s):

Atrial Fibrillation ◽

Overall Survival ◽

Stem Cell ◽

Platelet Count ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autonomic Neuropathy ◽

Control Group ◽

Al Amyloidosis ◽

The Impact

Abstract Aim: The autonomic nervous system plays an essential role in homeostasis and the response to stress. The peri-transplant period can be a challenging time for homeostatic responses due to the fluid shifts, sepsis and cardiac dysrhythmias that can occur. Patients with AL amyloidosis may have significant autonomic neuropathy (AN) that renders the peri-transplant care problematic. The purpose of this study was to compare a cohort of patients with AL amyloidosis complicated by AN with a matched cohort without AN to determine the outcome of patients with AN during and after stem cell transplantation (PBSCT). Methods: We performed a nested case-control study by searching the Mayo Clinic dysproteinemia transplant database for all patients with AL amyloidosis who underwent autologous PBSCT. Patients with proven AN were identified and compared to a large cohort of matched controls. We have complete follow-up on all the patients. The main outcome variables were overall survival (OS), the duration of hospitalization, incidence of sepsis, peri-transplant atrial fibrillation (AF) and engraftment kinetics. Comparisons between groups were performed with the Mann Whitney U test for continuous variables and the chi squared test for nominal variables. Overall survival was determined by the Kaplan-Meier method. A stepwise Cox proportional hazards model was used to evaluate the impact of various parameters on OS. Results: We identified 13 patients with AN who underwent PBSCT and compared them to a control group of 94 patients. The two cohorts were well matched for many of the relevant clinical and laboratory characteristics prior to PBSCT. Notable differences included (i) patients with AN tended to have more organs involved (2.5 versus 1, p<0.001) and as a result (ii) the conditioning dose of melphalan was often reduced (p=0.0015). There was no difference in the number of apheresis sessions required for CD34+ cell collection (2.5 versus 2.0, p=0.99), or the number of CD34+ cell collected (6.75 versus 8.15 x106/kg, p=0.99) between the two cohorts. The median hospital duration was 10 (1 – 78) and 8 (0 – 78) days (p=0.99) respectively. Engraftment kinetics, as measured by the time to reach a neutrophil count > 500/ml (p=0.85), a platelet count > 20,000/ml (p=0.99) and a platelet count > 50,000/ml (p=0.99) were similar in the two cohorts. Culture positive sepsis was more common in patients with AN (75% versus 47%, p=0.014). Atrial fibrillation occurred in all patients with AN but in only 1 patient from the control group (p<0.0001). The median OS from PBSCT was 45.2 months for all the combined groups. However, the median OS for patients with AN was 29 months but not yet reached for the controls (p<0.0001). On univariate analysis, cardiac involvement (p=0.0132), AN (p=0.0011), GFR (p=0.038), number of organs involved (p=0.0064) and NT-pro-BNP (p=0.039) all had an impact on OS. On multivariate analysis, AN remained an independent adverse determinant of OS. Conclusion: Patients with autonomic neuropathy secondary to AL amyloidosis can undergo PBSCT safely with similar engraftment kinetics. They are at a higher risk of peri-transplant atrial fibrillation and sepsis although their hospitalizations are not longer compared to controls. Patients with AN generally have more organ involvement by AL amyloidosis. However, AN is an independent, adverse determinant of OS in AL amyloidosis.

Download Full-text

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

Blood ◽

10.1182/blood.v114.22.1228.1228 ◽

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.

Download Full-text

Development of a Frailty Score for Older Patients with Myelodysplastic Syndromes and Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v114.22.1775.1775 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1775-1775

Author(s):

Barbara Deschler ◽

Gabriele Ihorst ◽

Uwe Platzbecker ◽

Ulrich Germing ◽

Michael Lübbert

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Activities Of Daily Living ◽

Cell Transplantation ◽

Daily Living ◽

Older Patients ◽

Treatment Allocation ◽

Frailty Score

Abstract Abstract 1775 Poster Board I-801 Introduction Treatment options in older patients (pts) with MDS/AML range from best supportive care (BSC) to intensive chemotherapy/hematopoietic stem cell transplantation (IC/HCT), with low-dose chemotherapy or novel non-intensive agents (e.g. hypomethylating agents; HA) as alternatives. Due to frequent age-related physical and/or mental impairments, intensive treatment is not always feasible. As the basis for treatment decision-making is not well defined, the generation of comprehensive assessments of age-specific functional and quality of life (QOL)-aspects in addition to disease-specific risk factor definition therefore is urgently needed. Geriatric Assessment (GA) is expected to offer rational support in this process. Patients and Methods Since January 2004, we have prospectively evaluated the prognostic impact of GA on overall survival (OS) in 195 consecutive pts ≥60 years (yrs) with AML (n=132) or MDS (n=63) in three participating centers, receiving either BSC or HA+BSC or IC/HCT. Of the pts receiving non-intensive treatment, 50% had MDS. GA included eight instruments evaluating QOL, activities of daily living, depression, mental functioning, mobility, comorbidities and performance status (PS). In addition, disease- and patient-specific laboratory parameters were obtained. Results Median age of pts was 71 yrs (range: 60-87 yrs). The primary treatment allocation was BSC in 47 pts (median age: 75 yrs); HA+BSC in 66 pts (74 yrs); IC/HCT in 75 pts (68 yrs). 62% of IC/HCT pts received a matched related/unrelated stem cell transplantation. Application of age-specific tests at the different study centers was readily feasible. The initial multidimensional GA was associated with treatment allocation, age, hematological and functional parameters and treatment outcome. Multivariate analyses revealed impairments in activities of daily living (ADL: Barthel Test, HR: 2.22) and fatigue (measured by EORTC QLQ-C30; HR: 1.68) as significant prognostic parameters for overall survival. Both risk factors were combined to construct a simple risk score for survival. Conducting a Cox regression model with established risk factors, a high risk frailty score in the entire pt population was associated with an elevated HR of 4.17 (p<0.0001), while adverse cytogenetics (AML), blasts >20% and comorbidities >1 proved to be independently associated with HRs of 2.491 (p=0.0001), 2.756 (p=0.0005) and 1.495 (p=0.1281). When this score was applied to pts receiving sole BSC or HA+BSC, highly significant differences in OS could be demonstrated, with p=0.0035 and p<0.0001, respectively. Conclusions Our data demonstrate that GA is a useful and objective tool in the in-depth evaluation process prior to treatment allocation in elderly patients with MDS/AML. A simple prognostic score based solely on ADL and fatigue to predict outcome of patients treated non-intensively has been established. Validation in independent cohorts appears warranted. Disclosures No relevant conflicts of interest to declare.

Download Full-text

High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning

Journal of Clinical Oncology ◽

10.1200/jco.2014.60.1203 ◽

2015 ◽

Vol 33 (21) ◽

pp. 2392-2398 ◽

Cited By ~ 34

Author(s):

Ran Reshef ◽

Austin P. Huffman ◽

Amy Gao ◽

Marlise R. Luskin ◽

Noelle V. Frey ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Unrelated Donor ◽

Cd8 Cells ◽

Cd8 Cell ◽

The Impact ◽

Reduced Intensity

Purpose To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. Patients and Methods We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. Results Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 108 CD8 cells per kilogram optimally segregated patients receiving CD8hi and CD8lo grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8hi graft, whereas approximately half of younger donors provided CD8hi grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8lo doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8hi doses (P = .03), but not for recipients of younger unrelated donor CD8lo grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. Conclusion Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT.

Download Full-text

Risk Factors and Outcomes for Patients With Follicular Lymphoma Who Had Histologic Transformation After Response to First-Line Immunochemotherapy in the PRIMA Trial

Journal of Clinical Oncology ◽

10.1200/jco.2015.65.7163 ◽

2016 ◽

Vol 34 (22) ◽

pp. 2575-2582 ◽

Cited By ~ 85

Author(s):

Clémentine Sarkozy ◽

Marek Trneny ◽

Luc Xerri ◽

Nick Wickham ◽

Pierre Feugier ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Follicular Lymphoma ◽

Disease Progression ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

International Prognostic Index

Purpose To study the outcome of histologic transformation (HT) in a large prospective cohort of patients with follicular lymphoma (FL) who previously responded to immunochemotherapy. Patients and Methods After a median 6-year follow-up of 1,018 randomly assigned patients from the PRIMA trial, disease progression was observed in 463 patients, 194 of whom had histologic documentation. Results Forty patients had histology consistent with HT, and 154 had untransformed FL (median time to recurrence, 9.6 v 22.8 months, respectively; P = .018). Thirty-seven percent of biopsies performed during the first year of follow-up showed HT corresponding to 58% of all HTs. Altered performance status, anemia, high lactate dehydrogenase level, “B” symptoms, histologic grade 3a, and high Follicular Lymphoma International Prognostic Index scores at diagnosis were identified as HT risk factors. Response (complete v partial) to immunochemotherapy or rituximab maintenance had no impact on the risk of HT. After salvage treatment, patients with HT had less frequent complete response (50.3% v 67.4%; P = .03) and more disease progression (28.2% v 9.6%; P < .001) than patients without HT. Estimated overall survival for the patients with HT was poorer (median, 3.8 v 6.4 years; hazard ratio, 3.9; 95% CI, 2.2 to 6.9). Autologous stem cell transplantation improved the outcomes of patients with HT (median overall survival, not reached v 1.7 years) but not of patients with persistent FL histology. Conclusion HT in patients with FL who previously responded to immunochemotherapy is an early event associated with a poor outcome that may deserve intensive salvage with autologous stem cell transplantation. These data emphasize the necessity for biopsy at the first recurrence of FL.

Download Full-text

Risk Factors for Blood Product Usage Following Sibling Allogeneic Haemopoietic Stem Cell Transplantation (allo-HCT).

Blood ◽

10.1182/blood.v110.11.2909.2909 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2909-2909

Author(s):

Nicola Hurst ◽

Charles G. Mullighan ◽

Sue L. Heatley ◽

Kathryn Robinson ◽

Silke Danner ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Platelet Transfusion ◽

Blood Product ◽

Disease Risk ◽

Red Cell ◽

Product Usage ◽

Transfusion Requirements

Abstract Red cell and platelet transfusion requirements have been reported to be lower following reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC allo-HCT) when compared to myeloablative (MA) allo-HCT. However, previous studies examined RIC regimens with lower haemopoietic toxicity than many of the regimens in use today. We investigated risk factors for red cell and platelet transfusion in patients enrolled prospectively in an Australian study investigating the non-HLA immunogenetics of sibling allo-HCT. The transfusion requirements in the first year post transplant were reviewed for 122 patients transplanted between 2002 and 2006 in three Australian transplant centres. Seventy-one patients received MA and 51 RIC regimens. Using regression analysis, the outcome variables of total red cell and platelet units transfused were analysed. The factors age, transplant centre, disease, transplant type (RIC v MA), days of neutropenia, death within 12 months, disease risk (high risk (HR) v standard risk (SR)) and ABO mismatch underwent univariate analysis. Associated variables with p<0.2 were included in a multivariable analysis. Duration of neutropenia, disease risk, death within 12 months and transplant centre were significantly associated with higher red cell and platelet usage (p<0.0001). Transplant type was not associated with transfusion requirement. Each additional day of neutropenia resulted in a 9% increase in number of red cell units transfused and 11% of platelet units. HR MA patients used an estimated 17 units of red cells compared to 12 units for SR. HR RIC patients used an estimated 26 units compared to 10 for SR RIC patients. HR patients used an estimated 16.9 platelet units compared to 8.5 for low risk. These data highlight the importance of disease risk and degree of myelosuppression as key risk factors for blood product usage following allo-HSCT.

Download Full-text

Cardiovascular Risk: Analysis of Known Factors in Patients After Treosulfan-Based Conditioning for Haploidentical and HLA-Identical Stem Cell Transplantation

Blood ◽

10.1182/blood.v118.21.4471.4471 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4471-4471

Author(s):

Alessandra Forcina ◽

Maria Teresa Lupo Stanghellini ◽

Raffaella Greco ◽

Alessandro Lorusso ◽

Daniela Clerici ◽

...

Keyword(s):

Cardiovascular Disease ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Lipid Profile ◽

Cell Transplantation ◽

Risk Score ◽

Cell Depletion ◽

Unrelated Donor ◽

The Impact

Abstract Abstract 4471 Allogeneic stem cell transplantation (HSCT) is an emerging risk factor for cardiovascular disease. Long-term survivors seem to be at higher risk for premature arterial vascular disease compared with sex- and age-matched population. In HSCT, pre-transplant treatments and the conditioning regimen play a key role in endothelial and organ damage. The use of immunosuppressant drugs to prevent graft-versus-host disease (GvHD) influences as well the development of cardiac disease. To better understand the impact of treosulfan-based conditioning regimens in leading to the emergence of cardiovascular disease, we retrospectively evaluated 94 consecutive patients who had survived longer than 1 year, transplanted at Our Institution between 2002 and 2010 (62 males – median age 46, range 14–69). For 48 patients an HLA-identical sibling was available, 6 patients found an unrelated donor while 40 patients underwent haploidentical HSCT from family donors. Forty-six patients received in vivo T-cell depletion and 72 B-cell depletion. GvHD prophylaxis was based upon cyclosporine + methotrexate for the HLA-identical transplants (48 – median EBMT risk score 3) whereas rapamycin + MMF were used for patients undergoing transplantation from HLA-haploidentical donors (35 – median EBMT risk score 4); 9 did not receive any immunosuppression because of application of suicide gene strategy as tool to prevent GvHD (median EBMT risk score 3). We compared clinical variables (i.e. GvHD, OS, TRM, major cardiac events and comorbidities) with biochemical and functional tests (i.e. cardiac function, lipid profile and ferritin levels) both before and 1 year after transplantation. After a median follow-up of 29 months, only 3 patients experienced a major cardiovascular event; no one experienced a late congestive heart failure. In all series, we found that ferritin levels significantly decrease after 1 year of follow-up, compared to pre-transplant values (P <0.0001); viceversa, the lipid profile (total cholesterol, HDL and LDL fractions) remarkably increased (p <0.05). Interestingly, the linear regression analysis for the overall survival showed no difference for both ferritin level and cholesterol level. Moreover, no significant variations were detected comparing cyclosporine versus rapamycin-treated patients, nor comparing patients with or without GvHD. Increased rates of cardiovascular disease are commonly associated to HSCT. In our experience, no differences were found in the incidence of cardiovascular events comparing different donor source or immunosuppressants. This suggests that haploidentical transplants are feasible and have similar cardiac toxicity than standard HLA-identical ones. Our analysis was surely limited by the short time of observation. In future, the evaluation of dynamic biomarkers on a greater series and on a longer follow-up will help us to identify a tailored schedule of cardiac monitoring after HSCT to prevent major lethal events in our patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

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

Blood ◽

10.1182/blood.v120.21.4186.4186 ◽

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.

Download Full-text