Autologous Stem Cell Transplantation in Multiple Myeloma Patients Over 60 Years Old

The incidence of Multiple myeloma (MM) increases with age; two-thirds of the patients are older than 65 years. Induction treatment, including new agents such as thalidomide, bortezomib, and lenalidomide followed by a conditioning regimen and upfront autologous stem cell transplantation (ASCT), has been accepted the standard treatment approach for newly diagnosed fit MM patients. We aimed to search the real-life data, the efficacy and safety of upfront ASCT following induction in patients with MM over 60 years old retrospectively. The data of MM patients who were ≥60 years old during autologous stem cell transplantation and treated at our center between 2010 and 2018 retrospectively analyzed. The study results were 63 patients included at the age of ≥ 60 years who underwent upfront ASCT. Median PFS was 15.5±2.6 months, and the median overall survival (OS) was 28.15±5 months. According to age groups, median PFS was 12±2.3 months in the 60-64 age group, 18.4±6 months in the 65-69 age group, and 26±15 months in the ≥70 age group. Median OS was 26.5±6.1 months in the 60-64 age group, 39.66±8.9 months in the 65-69 age group, and 18 months in the ≥70 age group. A significant relationship between the quantity of infused CD34+ stem cells and PFS and OS (p:0.05 and

Early Relapse After Autologous Stem Cell Transplantation in Multiple Myeloma is Still Prognostic in The Era of Novel Agents

Significant improvements in the prognosis of Multiple Myeloma(MM) have recently observed in the era of novel agents. Induction treatment, including new agents followed by conditioning regimen and upfront autologous stem cell transplantation(ASCT), has been accepted as the standard treatment approach for newly diagnosed eligible MM patients. Despite novel agents, upfront ASCT is still superior to conventional chemotherapy alone. Previous studies revealed that the duration between ASCT and relapse had predicted overall survival(OS), and meantime, it was widely used to determine the potential benefit from a second ASCT. However, the majority of the data collected reflects the treatment modalities before novel agents. In this study, we aimed to investigate the impact of post-transplantation early relapse(ER) on survival in the era of novel agents. The results of 155 MM patients that underwent ASCT at our center between January 2010 and May 2018 were analyzed retrospectively. The median follow-up duration was 20 months in the ER group, 27 months in the non-ER group, and 24 months in all patients. 33.3% of patients in the ER group and 71.4% of patients in the non-ER group were alive at the time of analysis. Median OS was 20.77±3.66 months in the ER group and 40.89±4.21 months in the non-ER group. We found a statistically significant relationship between the ER and the poor OS (p

The impact of bone marrow plasma cell percentage on progression free survival and overall survival in multiple myeloma patients who are in serological complete remission after autologous stem cell transplantation

Multipl Miyelom tedavisinde öncelikli hedef şifa sağlamak, bu hedefe ulaşılana kadar ise ilerlemesiz sağkalım, toplam sağkalım sürelerini uzatmak ve yaşam kalitesini arttırmaktır. Yüksek doz Melfalan ve OKHN ile daha iyi bir yanıt derinliği elde edilmesi, ilerlemesiz sağkalımı etkileyen önemli bir prognostik faktör olarak tanımlanmaktadır. Ancak serolojik olarak tam yanıt elde edilen hastalarda dahi farklı seyir olabilmekte ve bu hastalar prognoz açısından homojen olmayan bir grup oluşturmaktadır. Bu hasta grubunda OKHN sonrası minimal kalıntı hastalık tayini ilerlemesiz ve genel sağkalım açısından öngörü sağlayan bir parametredir. MM tanısıyla OKHN yapılan ve nakil sonrasında 1.ve/veya 3.ayında serolojik TY elde edilen hastaların kemik iliği biyopsi ve aspirasyonundaki plazma hücre oranları için %5 yerine daha düşük (%1.5 ve %2) eşik değerleri belirlenmiş ve daha düşük bir plazma hücre eşik değerinin ilerlemesiz ve genel sağkalım ile ilişkisi araştırılmıştır. Çalışma grubuna alınan Gazi Üniversitesi Tıp Fakültesi Hastanesi Erişkin Hematoloji Bilim Dalı Kemik İliği Nakil Ünitesi'nde 17.09.2003 13.05.2013 tarihleri arasında Multiple Myelom tanısıyla sadece bir kez otolog kök hücre nakli yapılan 124 hastadan OKHN sonrası 1. ve/veya 3.ayda serolojik olarak tam yanıt elde edilen 60 hasta çalışmaya dâhil edilmiştir. Çalışmaya 22 kadın (%36,7) ve 38 erkek (%63,3) hasta alındı. Ortanca yaş 57 (32 70) olarak hesaplandı. Hastalar OKHN'i takiben ortanca 35 (5 116) ay izlendi. Hastalarda cinsiyet, ISS'e göre risk evresi, nakil öncesi yanıt durumu, nakil öncesi MG varlığı, 1. ay plazma hücre oranı (kesme noktası ≤%1.5 ve >%1.5 veya kesme noktası ≤%2 ve >%2) ortanca 35 (5-116) ay izlem sonunda İSK'ı etkileyen değişkenler olarak bulundu (p0.05). Toplam sağkalımı etkileyen tek değişken ise OKHN sonrası 1. ay plazma hücre oranı (kesme noktası ≤%2 ve >%2) olarak bulundu (p=0.019). Bu tez çalışması ile OKHN sonrası serolojik TY elde edilen hastaların arasında daha agresif tümör biyolojisine sahip hastaların olabileceğini ve bu grup hastalar için riske dayalı bir takip ve tedavi stratejisi geliştirmek gerektiğini vurguladık. OKHN sonrası elde edilen tam yanıtın kısa süresi muhtemel hastaları öngörmekte daha düşük plazma hücre oranı eşiğinin kullanılabileceği, bunun pratik ve ucuz bir yöntem olduğu gösterilmiştir. Bu yöntem ile serolojik tam yanıttaki hastalar arasında farklı İSK ve TSK'ı olan alt grupların varlığını göstermek mümkün olmuştur.Cure remains the primary therapeutic goal in multiple myeloma while progression free survival (PFS), overall survival (OS) and quality of life are considered as the secondary targets. Response depth after high dose melphalan and autologous stem cell transplantation (ASCT) is accepted to be a significant indicator of PFS. However even the patients who are in complete remission are not homogeneous in terms of prognossis. Assesment of minimal residual disease after achieving serological complete remission is known to be a predictor of PFS and OS after ASCT. However there is no established standart method which is cost effective and applicable widely. We investigated the role of a lower plasma cell threshold in the bone marrow aspirate instead of the established 5% in stratifying the patients who achieved CR 1 and/or 3 months after ASCT into different prognostic groups. A total of 60 MM patients male/female : 38/22; median age : 57 (32-70) who underwent ASCT in the Stem Cell Transplantation Unit of Gazi University between 17.09.2003 - 13.05.2013 and achieved serological CR on the 1st and/or 3rd months of ASCT were included in the study. Gender, ISS risk score, pretransplant disease status, presence of pretransplant monoclonal gammopathy (MG) and the percentage of bone marrow plasma cells in the 1st month (cut-off level 1,5% or 2%) were found to have significant impact on PFS after a median follow-up of 35 (5 116) months (p0,05). The impact of the presence of pretransplant MG on PFS was also found to be nearly significant (p=0,051). Bone marrow plasma cell ratio in the 1st month of ASCT (cut-off level 2%) was the only parameter with a significant impact on OS (p=0,019). We determined the heterogenity of the prognossis even in MM patients who achieved a serological CR 1 and/or 3 months status post ASCT with using a lower plasma cell threshold of 1.5 and 2% and thus suggest that patients might benefit from risk adoptive threatment startegies under the guidance of plasma cell ratio. Prospective trials should investigate the role of risk adoptive post transplant startegies, such as further treating high risk patients with consolidation and maintenance protocols while protecting low risk patients from overtreatment with potential long and short term toxicities

Prognostic role of pre-transplantation serum C-reactive protein levels in patients with acute leukemia undergoing myeloablative allogeneic stem cell transplantation

The aim of this study was to identify indicators of outcome prior to transplantation in allogeneic hematopoietic stem cell transplantation (HCT). Clinical data of 106 patients with acute leukemia were retrospectively analyzed. We examined the role of pre-conditioning serum C-reactive protein (CRP) and ferritin levels, HCT-CI and European Group for Blood and Marrow Transplantation (EBMT) scores on transplant toxicities, transplant-related mortality (TRM), progression-free survival (PFS), and overall survival (OS). High pre-conditioning serum CRP levels showed a positive correlation with higher EBMT scores (p < 0.001), HCT-CI (p = 0.004), and ferritin levels (p < 0.001). In univariate Cox regression analysis, serum CRP =10 mg/L, serum ferritin =1500 ng/mL, and HCT-CI =3 had a significant adverse effect on OS. Serum CRP =10 mg/L and HCT-CI =3 predicted increased risk of TRM in univariate analysis. Multivariate Cox regression analysis showed that HCT-CI score =3 independently predicted increased risk of TRM and CRP =10 mg/L predicted increased risk of disease progression. Although CRP lost its significance on TRM in multivariate analysis, as an inexpensive and readily available serum biomarker of inflammation, the prognostic role of pre-transplant CRP levels should be analyzed in selected diseases and increased number of patient groups