scholarly journals IMPACT OF PRETRANSPLANT DONOR AND RECIPIENT CYTOMEGALOVIRUS SEROSTATUS ON OUTCOME FOR MULTIPLE MYELOMA PATIENTS UNDERGOING REDUCED INTENSITY CONDITIONING ALLOGENEIC STEM CELL TRANSPLANTATION.

2013 ◽  
Vol 5 (1) ◽  
pp. e2013026 ◽  
Author(s):  
Jean Elcheikh
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Grade Ii ◽  
Cmv Reactivation ◽  
Reduced Intensity

To investigate the impact of pre-transplant CMV serostatus of donor or recipient on outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). To our knowledge no data are available in the literature about this issue.We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer centre at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R]-) 17 patients (17.1%), intermediate risk (D+/R) 14 patients (14.1%), or high risk – either (D-/R+) 31 patients (31.3%) or (D+/R+), 37 patients (37.3%).Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26–318). Three patients (3%) developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs intermediate: 29% vs high: 50%; p=0.001) and the presence of grade II–IV acute GvHD (Hazard Ratio: HR=2.1 [1.1–3.9]). Thirty-six of the 39 patients (92%) with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II–IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM) were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005). Two-year overall and progression free survival were 56% and 34%, respectively.Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre-emptive treatment strategy could in part explain these results. Novel prophylactic measures such as immunotherapy and drug prophylaxis need to be considered in this specific group of patients, warranting further prospective studies.

scholarly journals Impact of Pretransplant Donor and Recipient Cytomegalovirus Serostatus On Outcome for Multiple Myeloma Patients Undergoing Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4496-4496
Author(s):  
Jean El-Cheikh ◽  
Raynier Devillier ◽  
Roberto Crocchiolo ◽  
Sabine Furst ◽  
Boris Calmels ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Partial Remission ◽  
Progressive Disease ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Grade Ii ◽  
Cmv Reactivation ◽  
Reduced Intensity

Abstract Abstract 4496 Purpose: To investigate the impact of pre-transplant CMV serostatus of donor or recipient on outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). Patients and methods: We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer centre at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R]-) 17 patients (17.1%), intermediate risk (D+/R) 14 patients (14.1%), or high risk – either (D-/R+) 31 patients (31.3%) or (D+/R+), 37 patients (37.3%). Results: Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26–318). Three patients (3%) developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs intermediate: 29% vs high: 50%; p=0.001) and the presence of grade II–IV acute GvHD (Hazard Ratio: HR=2.1 [1.1–3.9]). Thirty-six of the 39 patients (92%) with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II–IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM) were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005). Two-year overall and progression free survival were 56% and 34%, respectively. Conclusion: Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre-emptive treatment strategy could in part explain these results. Novel prophylactic measures such as immunotherapy and drug prophylaxis need to be considered in this specific group of patients, warranting further prospective studies. Legend: CR, complete remission; VGPR, very good partial remission; PR, partial remission, PD, progressive disease; Flu, fludarabine; Bu, busulfan; ATG, antithymocyte globulin; CR, complete remission; VGPR, very good partial remission; PR, partial remission, PD, progressive disease; MRD, matched related donor; URD, unrelated donor; GVHD, graft versus host disease; CSA, cyclosporine A; MMF, mycophenolate mofetyl. Disclosures: No relevant conflicts of interest to declare.

Cytomegalovirus Reactivation and Relapse Following Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5104-5104
Author(s):  
Revati Rao ◽  
Kevin Chin ◽  
Geoff Chan ◽  
Kellie Sprague ◽  
Andreas Klein ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Allogeneic Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Attributable Mortality ◽  
Reduced Intensity Conditioning ◽  
Cmv Reactivation ◽  
Reduced Intensity

Abstract Background: Recent studies have reported CMV reactivation rates of 42% to 65% in patients treated with allogeneic stem cell transplantation using reduced intensity conditioning regimens (RIT). However, published data on RIT patients who experience CMV reactivation, are treated successfully with antiviral therapy to eliminate detection, and who subsequently develop CMV relapse, is sparse. Methods: We performed a retrospective cohort analysis of 106 patients who underwent RIT at Tufts-New England Medical Center using a preparative regimen of pentostatin, extracorporeal photophoresis, and reduced total body irradiation, from 1997–2003. All patients received identical graft-versus-host disease (GVHD) prophylaxis, which consisted of IV cyclosporine and PO methotrexate. CMV serostatus was determined on all patients prior to transplant. All patients were screened weekly by CMV antigen capture assay after day +14. Patients did not receive CMV prophylaxis. CMV reactivation was defined as 2 consecutive positive (>2.1 pg/mL) CMV DNA measurements. CMV reactivation was treated with either Ganciclovir 5mg/kg IV daily or Valganciclovir 450mg PO BID until whole blood CMV DNA levels were no longer detectable. Patients were treated with antiviral therapy until a documented negative CMV DNA assay. Those found to have detectable CMV DNA after adequate therapy were then defined as having CMV relapse. Patients were also assessed for incidence of GVHD and mortality. Attributable mortality was defined as mortality in patients who had CMV relapse compared to those who had CMV reactivation without relapse. Fisher’s exact test was used to compare proportions, Kruskal-Wallis was used to compare means, and survival and time to reactivation and relapse were analyzed by Kaplan-Meier Results: Of 106 patients, 49 (46.2%) were CMV seropositive prior to transplant. Twenty -five (51%) of forty-nine CMV positive patients developed CMV reactivation at a median of 43 days (range 26 – 312 days) after receiving stem cells. Among patients with CMV reactivation, 36 were MRD and 13 were MUD. Nine (36%) of 25 patients with CMV reactivation developed CMV relapse. CMV relapse occurred at a median of 16 days (range 4 – 77 days) after CMV reactivation. CMV reactivation occurred earlier among those who relapsed (median 34 days, range 26 – 70 days) compared to those who did not relapse (median 55.5 days, 27 – 312 days, p=.03). Peak viral load was significantly higher in CMV relapsers (median 55.3 pg/mL, range 14.5 to 486.8) compared to non–relapse patients (median 4.4 pg/mL, range 2.1 – 58.2, p=. 0007). There was no difference in acute GVHD in the groups (100% vs. 75%, p=.26). However, those who did relapse had a higher incidence of chronic GVHD than those who did not (89% vs. 38%, p=.03). There was no difference in median survival between non-relapse and relapse patients (13 months vs. 16 months, p=. 99). The attributable mortality rate due to CMV relapse was 23%. Conclusions: Our results suggest there is a subgroup of patients who are at high risk for CMV relapse in the post RIT setting. Risks for CMV relapse include early reactivation and higher peak CMV viral loads. In addition, there was a higher risk of chronic GVHD in CMV relapse patients. We have identified a high- risk subset of patients who reactivate CMV for whom additional therapeutic strategies may be warranted.

Comparison between Anti-Thymocyte Globulin and Alemtuzumab and the Possible Impact of KIR-Ligand Mismatch in Melphalan/Fludarabine Dose-Reduced Conditioning Followed by HLA-Matched and Mismatched Unrelated Stem Cell Transplantation in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 980-980
Author(s):  
Nicolaus Kroeger ◽  
Brownen Shaw ◽  
Simona Iacobelli ◽  
Tatjana Zabelina ◽  
Karl Peggs ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Statistical Significance ◽  
High Dose ◽  
Grade Ii

Abstract We compared anti-thymocyte globulin (ATG-Fresenius median dose 60 mg/kg: n= 48) with alemtuzumab (Campath-1H 100mg: n=25) in 73 patients with multiple myeloma, who underwent dose-reduced conditioning with melphalan and fludarabine, followed by allogeneic stem cell transplantation from matched (n=63) or mismatched (n=10) unrelated donors. Patients of the ATG group had higher age (median 50 vs 47 years, p=0.05), more prior high-dose chemotherapies (p<0.001), while in the Campath group more bone marrow as stem cell source was used (p<0.001). No primary graft failure occurred in both groups. Patients receiving alemtuzumab had a significant faster engraftment of leukocyte (p=0.03) and of platelets (p=0.02) and a lower incidence of acute GvHD grade II-IV (24 vs 47%, p=0.05). However, after treatment with donor lymphocyte infusion due to persistent disease or mixed hematopoietic chimerism the difference of acute GvHD grade II-IV between alemtuzumab and ATG treated patients did not reach statistical significance (32 vs 47%, p=0.2). No difference in incidence of chronic GvHD was observed (25 vs 33%, p=0.6) More CMV seropositive patients in the alemtuzumab group experienced CMV reactivation (100% vs 47%, p=0.001). The cumulative incidence of treatment related mortality at 2 years for ATG and Campath was 29.3% (CI=17–50%) vs 28.5% (CI=15–54%), p=0.7. No significant difference could be observed in the estimated 2 years OS and PFS between ATG and Campath: 53% (CI:38–75) vs 45% (CI:28–73) and 29% (CI:16–54) and 36% (CI: 20–62), respectively. For PFS, in a multivariate analysis relapse to prior high-dose chemotherapy was the strongest negative factor: HR 2.9, p= 0.001. Including only those patients who did not experienced any relapse at time of allogeneic stem cell transplantation the Campath-group had a 2.5 fold higher risk of progression in comparison to the ATG group, but without reaching statistical significance (HR: 2.5, p=0.15). Ten out of 73 patients had KIR-ligand mismatch in GvH direction. While in patients without KIR-ligand mismatch the cumulative incidence of relapse at two years was 50%, none of the KIR-ligand mismatched patients relapsed so far (p=0.02). The immunosuppressive effect from Campath is stronger than ATG resulting in less acute GvHD, but requires more DLI procedures to control diseases and resulted in a trend to a lower PFS in chemosensitive patients. This preliminary data further implicated a major role of KIR-ligand mismatch transplantation in multiple myeloma

CD8-Depleted Donor Lymphocyte Infusions Can Boost Immune Reconstitution after Haploidentical Stem Cell Transplantation Following Reduced-Intensity Conditioning Regimen.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3138-3138 ◽  
Author(s):  
Paolo Corradini ◽  
Anna Raganato ◽  
Cristiana Carniti ◽  
Matteo Carrabba ◽  
Farina Lucia ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Immune Reconstitution ◽  
Acute Gvhd ◽  
Mean Value ◽  
Reduced Intensity Conditioning ◽  
Reduced Intensity

Abstract Haploidentical stem cell transplantation (SCT) can be used in relapsed haematological malignancies for patients lacking a matched sibling or unrelated donor. Major barriers of this strategy are the poor immune reconstitution and the high risk of relapse. Here, we report results of a phase I–II trial evaluating early add-backs of CD8-depleted donor lymphocytes (DLIs) (from 1x10^4 up to 1x10^5 cells/kg starting at day+45 up to day +105 at monthly intervals) after a reduced intensity conditioning (RIC) regimen [thiotepa (10 mg/kg), fludarabine (120 mg/sqm), cyclophosphamide (60 mg/kg) and TBI (2 Gy)]. Ex-vivo and in-vivo TCD were carried out by CD34+ cell selection using the CliniMACS device and alemtuzumab (15mg/m2, day-2), respectively. Twenty-one patients [n= 10 NHL (n=5 CLL, n=5 high-grade NHL), n=7 HL, n=1 MM, n=1 ALL, n=2 AML] were transplanted with advanced disease: 16 (76%) failed a previous autograft and 13 (62%) had refractory disease. A median of 10.4x10^6/Kg CD34+, 1x10^4/kg CD3+, 10x10^4/kg CD19+, 0.9 x10^4/kg NK+ were infused. All patients engrafted with full donor chimerism from day +90. At a median follow-up of 12 months (range, 4–41 months), 12 of 21 pts are alive (7 CR, 2 PR and 3 PD) and 9 died [n=3 infection with GVHD (+610, +187, +253), n=6 disease]. The estimated 2-year overall survival was 49%: pts transplanted in remission had better outcome (83% versus 31%, p=0.13). The estimated 2-year cumulative incidence of TRM and relapse were 27% and 58%, respectively. CMV reactivation and hospital readmissions for opportunistic infections occurred in 76% and 57% of patients, respectively. For CD8 depletion of donor leukaphereses, a new depletion protocol using clinical grade CD8 microbeads (Miltenyi) was applied. This procedure is efficient to reduce the content of CD8 T cells by 3 logs while the median cell recovery of CD3+, CD4+, CD56+/CD3+, CD 20+ was 60%, 86%, 54%, 72%, respectively. Before DLIs, only 2 of 21 patients (10%) developed acute GVHD (no grade III–IV). A total of 36 CD8-depleted DLIs were administered to 17 pts without any acute toxicity. Following DLIs, 6 pts (35%) developed acute GVHD (grade II) and 5 (30%) chronic GVHD (n=2 limited, n=3 extensive). Overall, the incidence of acute GVHD is higher (50% vs 22%, p=0.33) in pts receving larger numbers of donor cells (10–15x10^4/kg versus 3–5x10^4/kg CD8-depleted DLIs). The median values of CD4+/uL, CD8+/uL and NK+ were 100, 280 and 680 at 4 months and 220, 200, 500 at 6 months after SCT in patients receiving CD8-depleted DLIs. Measurable TREC/ucg DNA (mean value 316; mean value donors 3740) and polyclonal T cell repertoire, evaluated by spectratyping, were observed at 9 months in patients younger than 40 years and/or without GVHD. Our results suggest that: haploidentical SCT with RIC regimen provides high engraftment rate T-cell addback allows the achievement of more than 100/uL CD4+ at 4 months after SCT in the majority of patients Survival rate is promising in patients who had transplantation in remission suggesting that this strategy should be evaluated earlier in high risk haematological diseases.

Duration of Initial Admission and Subsequent Readmission in the First 100 Days Following Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1999-1999
Author(s):  
Moez Dungarwalla ◽  
Joy Brennan ◽  
Samar Kulkarni ◽  
Radovan Saso ◽  
Bronwen Shaw ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Short Term ◽  
Post Transplant ◽  
Cmv Reactivation ◽  
Reduced Intensity

Abstract Allogeneic stem cell transplantation (allo-SCT) after a reduced intensity conditioning (RIC) protocol is associated with decreased transplant related organ toxicity and mortality. Some authors have suggested that RIC allo-SCT be performed entirely in the outpatient setting. As a challenge to this hypothesis we examined the short term toxicity following RIC allo-SCT particularly focusing on duration of initial admissions and subsequent readmissions in the first 100 days post transplant. We analysed 104 consecutive RIC allo-SCT (median age: 52, range 19–67 yr; M: 69%, F:31%) performed at our institution between February 2003 and May 2007. All patients had a high risk haematological malignancy (27% Acute Myeloid Leukaemia, 20% Multiple myeloma, 20% Chronic Lymphocytic Leukaemia, 12% Lymphoma, 6% Myelodysplastic syndrome, 6% Acute Lymphoblastic Leukaemia, 6% Chronic Myeloid Leukaemia, 2% other). Conditioning was with fludarabine plus either melphalan, busulphan, cyclophosphamide or low dose TBI (2Gy). T cell depletion in vivo with alemtuzumab was utilised in 64%. Donor was matched related (39%) or unrelated (61%). Source of stem cells was PBSC (80%) or marrow (20%). GVH prophylaxis was CyA either alone or in combination with short term methotrexate. Patients were hospitalised from the beginning of the conditioning regimen until haematological and non-haematological toxicities had resolved. Eleven patients (10%) died before discharge. The median time required for achievement of neutrophil engraftment was 15 days (range 0–56). Four patients died prior to engraftment. Median duration of initial hospital admission was 31 days (range 17–192). In univariate analysis patients with Multiple myeloma were discharged earlier (p=0.001). Patients conditioned with Flu TBI were also discharged earlier (p&lt;0.0001). Unrelated donor RIC allo-SCT were discharged later (p&lt;0.001). Patients receiving alemtuzumab were also discharged later (p&lt;0.001). Readmissions within 100 days of transplant were documented in 50/104 (48%). The most common reasons were non CMV infections (30%), GVHD (22%), CMV reactivation (22%) and progressive disease (9%). Patient diagnosis, stem cell source, donor type, conditioning regimen, T cell depletion and age had no significant bearing on the incidence of readmission in the first 100 days post transplant by multivariate analysis. Transplant related complications (Infections, CMV reactivation, GVHD, TTP) were seen in 73/104 (70%) within 100 days of transplant. Transplant related mortality (TRM) at 100 days was 15%. Patients who required readmission in the first 100 days post transplant had lower OS at 1 year (45% v 73%) than those who did not require readmission (p&lt;0.001). The mean duration of readmissions in the first 100 days post transplant was 15.5 days. This had major financial implications with average bed costs of £7750 per readmission. In summary, although RIC regimens have undoubtedly widened the potential application of allo-SCT they are not without short term toxicity. Although early discharge following RIC allo-SCT has been advocated, our analysis demonstrates that the risk of readmission in the first 100 days post transplant is significant and is associated with increased costs and mortality. A full health economic analysis will be presented including a comparison with full intensity conditioning allo-SCT performed over the same period.

Circulating Microparticles As Predictive Biomarkers of Acute Graft Versus Host Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5778-5778
Author(s):  
Thiago Xavier Carneiro ◽  
Daniella Gregolin Marrese ◽  
Melina Gonçalves dos Santos ◽  
Matheus Vescovi Gonçalves ◽  
Yana Sarkis Novis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Graft Versus Host ◽  
Circulating Microparticles ◽  
Reduced Intensity ◽  
Neutrophil Engraftment

Abstract Background Graft-versus-host disease (GvHD) remains a leading cause of morbidity and mortality among allogeneic stem cell transplantation (SCT) patients. New research focusing on diagnostic methods and therapeutic interventions is required. Microparticles (MP) are structures ranging from 0.1 to 1 µm that are derived from the cell membranes of different cellular subtypes. The majority of circulating microparticles are derived from megakaryocytes (platelets) and erythrocytes. These structures have been described as biomarkers of cellular damage, activation, and intercellular signaling in in several autoimmune and vascular diseases. Whether the biologic events that characterize GvHD can alter the shedding of microparticles has not been described. Methods Patients who underwent allogeneic stem cell transplantation between august 2012 and September 2014 at the Hospital Sirio Libanes (Sao Paulo, Brazil) were included. Adult and pediatric patients were consecutively enrolled if neutrophil engraftment was achieved. Circulating MP were isolated and quantified by flow citometry. Annexin V-positive (total microparticles - TMP), CD61+ platelet-derived microparticles (PMP) and CD235+ erythrocyte-derived microparticles (EMP) were measured at neutrophil engraftment. Results MP were studied in the plasma of 48 patients. The levels of PMP were not associated with the risk of acute GvHD. However, the cumulative incidence (CI) of aGVHD was significantly increased among the patients with EMP counts above 360/µL at engraftment (59% vs. 26%, P=0.04). Higher EMP counts were associated with increased incidence of skin aGVHD (53% vs. 17%,P=0.02) and liver aGVHD (33% vs. 0%, P=0.002). There was no significant association between higher EMP count and incidence of gastrointestinal (GI) aGVHD (42% vs. 20%, P=0.10). The microparticles counts at engraftment were influenced by the intensity of the conditioning regimen. When compared with reduced intensity regimens, myeloablative regimens were associated with significantly higher EMP counts (152 vs. 349/µL, P=0.03). In patients exposed to reduced intensity conditioning regimens, a stronger association of a high EMP count and acute GvHD was observed (89% vs. 23%; p=0.002). A high EMP count was predictive of skin aGVHD (78% vs. 14%, P=0.002), liver aGVHD (67% vs. 0%, P<0.001), and GI aGVHD (72% vs. 20%, P=0.006). Conclusion Our data suggest that higher counts of erythrocyte-derived microparticles at engraftment may be associated with a greater risk of acute GVHD. Figure 1 Cumulative incidence of aGVhD II-IV (a), skin aGVhD (b), liver aGVhD (c) and GI aGVhD (d) in patients with high EMP count vs. low EMP count at engraftment. Figure 1. Cumulative incidence of aGVhD II-IV (a), skin aGVhD (b), liver aGVhD (c) and GI aGVhD (d) in patients with high EMP count vs. low EMP count at engraftment. Figure 2 Cumulative incidence of aGVhD (a), skin aGVhD (b), liver aGVhD (c) and GI aGVhD (d) In the subgroup of patients exposed to reduced intensity conditioning for patients with high EMP count vs. low EMP count at engraftment. Figure 2. Cumulative incidence of aGVhD (a), skin aGVhD (b), liver aGVhD (c) and GI aGVhD (d) In the subgroup of patients exposed to reduced intensity conditioning for patients with high EMP count vs. low EMP count at engraftment. Disclosures No relevant conflicts of interest to declare.

scholarly journals Survival Analysis in Patients with Multiple Myeloma after Allogeneic Hematopoietic Stem Cell Transplantation, a Single Center Study (1994-2013)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1233-1233
Author(s):  
Susanne Hofmann ◽  
Lisa Müller ◽  
Stephanie Harsdorf ◽  
Christian Langer ◽  
Peter Liebisch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Risk Group ◽  
High Risk Group ◽  
Grade Ii ◽  
The Impact

Abstract Introduction The role of allogeneic stem cell transplantation (allo-HSCT) in the treatment algorithms for patients with multiple myeloma remains controversial although it is the only potentially curative approach currently available. Here we present the retrospective analysis of 95 allo-HSCT performed between 1994 and 2013 at Ulm University Hospital. We focused on the impact of cytogenetics, graft-versus-host disease (GvHD) and intensity of conditioning on overall survival (OS), progression- free survival (PFS), relapse and non-relapse mortality (NRM). Study population Median age at initial diagnosis was 49 years (range 25-64), median age at time of allo-HSCT was 51 years (range 26-65). Median time from initial diagnosis to allo-HSCT was 13 months (range 3-106). Indications for allo-HSCT were 1) primary allo-HSCT after induction therapy (11 pts), 2) planned tandem auto-allo-HSCT (44 pts), 3) relapse after single allo-HSCT (25 pts), 4) relapse after tandem-auto-HSCT (15 pts). The conditioning regimen in 60 pts was a reduced intensity conditioning (RIC), in 35 pts myeloablative conditioning (MAC). In 68 pts cytogenetic data were available: 13 pts were stratified into standard-, 39 pts into the intermediate- and 16 pts into the high-risk group according to the mSMART recommendations. Results: Median follow-up was 70 months (95% CI, 64,5-75,5). The estimate 1-, 2- and 5-year OS was 87,4 %, 74,7 % and 46,4 % with a median OS of 36 months (95 % CI, 19,7 -52,2). For both, RIC and MAC median OS was 36 months (95% CI, 24,4–47,6 versus 95% CI, 0-108,4). The cumulative incidence of TRM was not different for RIC and MAC but there was a trend for lower relapse in patients receiving MAC (p=0,0612). With respect to the indication for allo–HSCT outcomes were as follows: Median OS was 89 months for primary allo-HSCT, 47 months for tandem auto-allo-HSCT, 20 months for relapse after auto-HSCT and 26 months for relapse after double auto-HSCT. OS did not differ significantly. Median OS in the standard risk group was 20 months (95% CI, 6,7-33,3), in the intermediate group 41 months (95% CI, 17,3-64,7) and in the high-risk group 7 months (95% CI, 0-14,8), showing no statistical significance. 1-year OS was 61,5% vs 66,7% vs 43,8%, 2-year OS was 35,9% vs 66,7% vs 43,8% and 5-year OS was 35,9% vs 43,2% vs 11,7% (standard vs intermediate vs high risk). The median PFS was 12 months (95% CI 8,4-15,6). 1-year PFS was 49,2%, 2-year PFS 32,9% and 5-year PFS was 21,8%. PFS according to the cytogenetic aberration showed a median PFS of 20 vs 14 vs 5 months, 1-year PFS was 53,8% vs 51,3 % vs 30 %, 2-year PFS with 35,9% vs 30,8% vs 7,5%, and 5-year PFS with 26,9% vs 11,5 % vs 7,5% (standard vs intermediate vs high risk). These differences are not statistically significant. Considering the impact acute GvHD, OS significantly differed between the groups with no aGvHD or aGvHD grade I and aGvHD grade II-IV with inferior survival for patients suffering from aGvHD grade II-IV. Chronic GvHD had no impact on outcome. Conclusion Our data of a 19 year experience in treatment of patients with advanced multiple myeloma with allo-HSCT showed an effective treatment option with a curative potential even for patients after intensive pretreatment including autologous stem cell transplantation. Patients who received MAC had a trend for lower cumulative incidence of relapse compared to RIC without increasing TRM in our study. Disclosures No relevant conflicts of interest to declare.

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