scholarly journals 145: Reduced Intensity Conditioning (RIC) is Associated with Shorter Duration of Chronic GVHD than Myeloablative Conditioning and Provides Very Good Quality of Life for Long-Term Survivors after Allogeneic Stem Cell Transplantation

2008 ◽  
Vol 14 (2) ◽  
pp. 55
Author(s):  
A. Shimoni ◽  
I. Hardan ◽  
N. Shem-Tov ◽  
A. Rand ◽  
E. Ribakovsky ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Chronic Gvhd ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Long Term Survivors ◽  
Reduced Intensity

Long-Term Survival and Quality of Life Assessment After Allogeneic Stem-Cell Transplantation; Comparable Results Following Myeloablative and Reduced-Intensity Conditioning,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4096-4096
Author(s):  
Avichai Shimoni ◽  
Eran Tallis ◽  
Noga Shem-Tov ◽  
Yulia Volchek ◽  
Ronit Yerushalmi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloablative Conditioning ◽  
History Of ◽  
Disease Free ◽  
Reduced Intensity

Abstract Abstract 4096 Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for patients (pts) with various hematological malignancies. SCT is associated with substantial mortality during the first 2 years after SCT whereas after 2 years survival curves often reach a plateau. However, late mortality and late events continue to cause treatment failures through the late post-transplant course. Quality of life (QoL) is increasingly recognized as an important long-term end-point. The pattern of late events and QoL has been reported following myeloablative conditioning (MAC) but is not well defined in the reduced-intensity (RIC) setting. To explore late outcomes we retrospectively analyzed SCT results in a cohort of 726 pts given allogeneic SCT between 1/2000 and 8/2009. Pts meeting standard eligibility criteria were given MAC (n=207) while pts considered at excessive risk for non-relapse mortality (NRM) were given fludarabine based RIC (n=385) or reduced-toxicity myeloablative conditioning (RTC, n=134). 246 pts were alive and disease-free 2 years after SCT. Their median age was 51 years (17–72). Diagnoses included AML/MDS (n=131), ALL (n=24), lymphatic diseases (n=48), CML/MPD (n=29), non-malignant (n=14). Donors were HLA-matched siblings (n=151), unrelated (n=91) or alternative donors (n=4). Conditioning was MAC (n=72), RIC (n=118) or RTC (n=56). At 2 years after SCT, 172 pts had a history of chronic GVHD, graded as moderate-severe (mod-sev) in 44% and 29% of pts after MAC and RIC/RTC, respectively (p=0.03). 68% and 43% of pts were still on immune suppressive therapy (IST) 2 years after SCT, respectively (p=0.001). With a median follow-up of 68 months after SCT (range, 25–140), the probability of pts surviving disease-free 2 years after SCT to remain alive and disease-free for the next 5 years was 84% (95CI, 75–93) and 82% (95CI, 75–89) after MAC and RIC/RTC, respectively (p=NS). There were 35 deaths beyond 2 years, 15 due to relapse and 20 due to NRM. NRM included 9 deaths due to second cancers; 2 due to relapse of a primary malignancy in pts transplanted for therapy related AML, 4 other solid tumors, 3 donor MDS/AML. 9 pts died of chGVHD/infections and 2 of myocardial infarction. In all, the cumulative incidence of late NRM was 7% (4–11), similar after MAC and RIC/RTC. However, more pts in the MAC group died of chGVHD/ infections (6.9% Vs 2.3%, p=0.08), while more pts in the RIC/RTC group died of second cancers (4.6% Vs 1.4%, p=NS). 24 pts relapsed, 25–102 months after SCT, cumulative incidence 11% (7–16); 9% after MAC and 11% after RIC/RTC (p=NS); 15 died, 9 are alive following further therapies. The kinetics of late relapses was similar with MAC and RIC/RTC. Advanced age (>55) and moderate-severe chGVHD were the most significant predicting factors for shortened survival. OS 5 years after the 2-year time-point was 77% and 89%, in the older and younger groups, respectively (p=0.05). OS was 78% and 90% in pts with and without mod-sev chGVHD, respectively (p=0.004). Multivariate analysis confirmed these as independent factors, HR 2.1 (p=0.07) and 2.6 (p=0.006), respectively. The conditioning regimen, disease type and status at SCT and donor type were not predictive. A history of mod-sev chGVHD predicted for NRM, HR 5.2 (p=0.001). Advanced disease status at SCT predicted for relapse risk, HR 2.6 (P=0.004). The cumulative probability of stopping IST by 8 years after MAC and RIC/RTC SCT was 59 and 75%, respectively (p=0.001). For patients who stopped IST the median duration of IST was 30 and 20 months, respectively (p=0.05). QoL was assessed by the EORTC QLQ-C30 questionnaire. Mean QOL score was 69, 66 and 65 after MAC, RIC and RTC, respectively. A low QOL score (20 points below median) was reported by 15%, 14% and 19%, respectively (p=NS). There was no difference in any of the other domains of QoL assessment as well. Multiple regression analysis identified continuous need IST and reporting depression as factors correlated with a low score while a healthy lifestyle (including return to work, physical and sexual activity) and academic education were associated with high score. In conclusion, the pattern of late outcome is similar after MAC and RIC/RTC. Late NRM is similar although chGVHD is less severe and the required duration of IST is shorter after RIC/RTC. This may lead to better QoL. Younger pts who are disease-free 2 years after SCT, particularly those with no mod-sev chGVHD can expect good long-term outcome and relatively good QOL. Disclosures: No relevant conflicts of interest to declare.

Reduced-Intensity Conditioning Is Associated with Shorter Duration of Chronic GVHD Than Myeloablative Conditioning and Provides Very Good Quality of Life for Long-Term Survivors after Allogeneic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1668-1668
Author(s):  
Avichai Shimoni ◽  
Izhar Hardan ◽  
Noga Shem-Tov ◽  
Avital Rand ◽  
Elena Ribakovsky ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Acute Leukemia ◽  
Chronic Gvhd ◽  
Cumulative Probability ◽  
Reduced Intensity Conditioning ◽  
Lymphoid Malignancies ◽  
Long Term Survivors

Abstract Reduced-intensity conditioning (RIC) has been increasingly used over the last decade as a curative approach for patients (pts) not eligible for myeloablative (MA) conditioning. It is now established that RIC can allow consistent engraftment and reduce toxicity of allogeneic stem-cell transplantation (SCT). However, the long-term effects, and in particular the duration of immunosuppressive therapy (IST) needed and quality of life of long-term survivors are less defined. To explore these issues we analyzed the results of 48 pts given SCT with RIC from 1/2000 to 8/2002, such that survivors have at least 5 year follow-up, and compared them to results of 41 SCT with MA conditioning given during the same period. The RIC group included older pts than the MA group, median age 49 (range, 20–65) and 37 (range, 20–65), respectively (p=0.01). The MA group included more pts with acute leukemia/MDS (68% vs 33%, p=0.001) while pts with myeloma were only given RIC (31% of the RIC group, p< 0.001). 48% of pts in the RIC group had a prior autologous SCT compared with none in the MA group (p< 0.001). There was no difference in donor type, 26% of all pts were given SCT from unrelated donors. After a median follow-up of 6.1 years (range, 5.1–7.6) 40 pts are alive, 20 after RIC and 20 after MA conditioning with estimated survival of 42% (95ci, 28–56) and 47% (95ci, 31–63), respectively (p=NS). Long-term survival with RIC was achieved across all diagnoses including 6 of 16 pts with acute leukemia/MDS, 6 of 6 pts with CML, 3 of 11 pts with lymphoid malignancies and 5 of 15 pts with myeloma. The corresponding rates for acute leukemia/MDS, CML and lymphoid malignancies in the MA group were 13 of 28, 3 of 4 and 4 of 9, respectively. Chronic GVHD occurred in 22 pts after RIC and in 26 pts after MA conditioning with a cumulative incidence of 48% (35–65) and 66% (53–83), respectively (p=0.07). 12 of 22 pts with chronic GVHD after RIC were eventually able to stop IST, 9 died on IST (relapse-5, non-relapse mortality (NRM)-4) and only 1 of 20 long-term survivors was still on IST at last follow-up. The median duration of IST was 17 months and the cumulative probability of stopping IST after 5 years (with relapse been competing risk) was 79%. In the MA group 10 of 26 pts with chronic GVHD were able to stop IST, 8 died on IST (relapse-6, NRM-2) and 8 of 20 long-term survivors were still on IST at last follow-up. The median duration of IST was 41 months (p=0.05) and the cumulative probability of stopping IST after 5 years was 48% (p=0.001). Two women gave birth in the RIC group while 2 men in the MA group fathered children spontaneously. There was one secondary malignancy in the MA group and none in the RIC group. Two pts in the MA group sustained myocardial infarction (one fatal) compared to none of the RIC group. One pt in the RIC group had reversible nephrotic syndrome. In summary long term(>5y) survival is similar for both RIC and MA SCT, however IST is significantly shorter after RIC and quality of life seems better. Overall, all 20 pts surviving more than 5 years after RIC SCT sustained excellent quality of life and only one still required IST. The more rapid achievement of transplantation tolerance with RIC may relate to better preservation of thymic function, but this requires further investigation. These observations require further confirmation in larger registry studies.

Factors Affecting Quality of Life During and After Stem Cell Transplantation in Long Term Survivors – Comparison of Autologous and Allogeneic Stem Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 590-590
Author(s):  
Katerina Benesova ◽  
Marie Trnkova ◽  
Miriam Lanska ◽  
Veronika Valkova ◽  
Katerina Steinerova ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Well Being ◽  
Myelogenous Leukemia ◽  
Long Term Survivors

Abstract Abstract 590 Background: Myeloblative conditioning (MAC) or reduced intensity conditioning (RIC) followed by autologous or allogeneic stem cell transplantation (ASCT or AlloSCT) is established and lifesaving treatment in selected indications. The quality of life (QoL) is then very important issue for long term surviving patients. The majority of data is often based on single center evaluation with limited number of patients. Therefore we have started the cross-sectional QoL project and this analysis is based on data collected from eight transplant centers. Methods: Altogether data from 1399 patients are included in the study. The FACT-G questionnaire (Q) was used for this analysis. The questionnaire consists of four parts - physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB). The patients completed the Q before the transplantation (at the time of indication or at the time of admission to SCT) n=304, after ASCT n=662 and after AlloSCT n=433. Patients were divided into 7 groups – before SCT, day +100, up to 1y, 1–2y, 2–3y, 3–5y and more than 5y. The clinical characteristics were obtained from national transplant registry; the data was cleaned and updated. Wilcoxon and Kruskall-Wallis tests were used for statistical analysis. Patient′s characteristic: The ASCT and AlloSCT groups (grp.) consist of 869 and 530 pts resp. including 207 pts before ASCT and 97 before AlloSCT. There were 52.8% and 55.7% men in ASCT and AlloSCT grp. resp. The median age in ASCT and AlloSCT grp. resp. was: 55.2 and 43.2y resp., the median follow-up 4.4 and 4.5y resp. The most frequent diagnosis of ASCT group were: Non-Hodgkin′s lymphoma (NHL) 46.1%, multiple myeloma (MM) 36.6%, Hodgkin′s lymphoma (HL) 8.5%. In AlloSCT: acute myelogenous leukemia 29.4%, acute lymphoblastic leukemia 15.7%, chronic myeloid leukemia 11.5% and myelodysplastic syndrome 10.0%. Disease progression/relapse was observed in 148 ASCT (22.4%) and 61 AlloSCT (14.1%) pts. In AlloSCT group MAC was used in 33% pts and matched unrelated donor (MUD) in 59.8% pts., aGVHD gr I-II was observed in 40.3% and gr III-IV 4.2% pts, cGVHD in 37.9% pts. Results: Significant differences in overall QoL before, during and after the AlloSCT (p<0.001) and ASCT (p=0.01) were observed. The QoL was improved from 1y after ASCT as well as from 2y after Allo-SCT. It was due mainly to the PWB and FWB improvement in both SCT groups, SWB and EWB remained unchanged. Long term survivors reported better QoL vs pts before transplant both in the alloSCT gr. (89 vs 80.7 points) as well as in ASCT gr.(82 vs 73.1). Interestingly, significantly better QoL in AlloSCT vs ASCT gr. was reported in all time points except day +100 and 2y. At the time of indication it was 80.7 vs 73.1 (p=0.035) and the most significant difference was among long-term survivors 89.0 vs 82.0 (p<0.001). The overall QoL was not affected by gender, women only reported better SWB in AlloSCT and ASCT grp. and men reported better EWB in ASCT gr. The age had significant impact on overall QoL in ASCT (p=0.005) and AlloSCT (p=0.006) but only due to difference in PWB and FWB resp., which was more profound in AlloSCT (p<0.001). The diagnosis had no impact on QoL in AlloSCT grp. but the MM pts have significantly lower QoL compared to NHL and HL pts. resp. (73 vs 80 vs 82 resp. p<0.001) in ASCT group. There was no significant impact of MAC or RIC on the QoL, patients with MUD has lower QoL compared to sibling donor (84.8 vs 88, p<0.05). Relapse after transplantation was associated with worse QoL, after ASCT 74 vs 81 (p=0.02) and after AlloSCT 81.5 vs 87.5 (borderline significance p =0.065). The long term survivor′s QoL was not affected by aGVHD in contrast to the cGVHD which significantly affects QoL (p<0.001) due to lower PWB (p<0.001) and FWB (p<0.001). Conclusion: We herein demostrate on large cohorts of pts that long term survivors have significantly better QoL compared to QoL in the time of indication of the transplantation and the improvement starts from 1y after ASCT and from 2y after AlloSCT. AlloSCT survivors report better QoL compared to the ASCT survivors. The most important factors affected QoL are age, cGVHD (AlloSCT) and diagnosis (ASCT), the borderline factors are relapse after SCT and type of donor (AlloSCT). Disclosures: No relevant conflicts of interest to declare.

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