Analysis of Risk Factors for Overall Survival at 5 Years in 96 Patients after Allogeneic Hematopoietic Cell Transplantation.

Abstract Abstract 4669 The aim was to analyze the risk factors for overall surrival at 5 years in 96 patients undergoing allogeneic hematopoietic stem cell transplantation by retrospec- tive analysis. 11 clinical parameters were selected for univariate analysis by using a Cox regression: age, sex, morbid rate, HLA locus, donor type, donor-recipient blood type, conditioning regimen, aGVHD, HC, VOD and IP. Factors significant at the 0.1 level on univariate analysis were evaluated by multivariate analysis by a Cox regres- sion. The cumulative incidence of aGVHD and patients survival rate were calculated by the method of Kaplan and Meier. 95 patients achieved sustained donor engraftment except one patients not. The median time of leukocyte engraftment was 13 days. The incidence rates of grades I∼IV acute GVHD was 43.75%.one of grades I aGVHD was 11.46%,gradesIIaGVHD was 19.79%,grades III∼‡WaGVHD was 12.50%. Ten patients relapsed and 38 dead,the overall survival at 5 years was 60.42%. The COX method analysis showed that aGVHD and disease states at transplant significantly im- proved OS. In conclusions, The key to improve the outcome of allo-HSCT is to red- uce the incidence and severity of aGVHD, meanwhile selecting the suitable disease state of CR1 at transplantation to treat the patients in advanced refractory and recure- nt situation. Disclosures: No relevant conflicts of interest to declare.

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Multivarite Analysis of Risk Factors for Affected Patients Long-Term Persistent Survival after Allogeneic Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood.v112.11.4292.4292 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4292-4292

Author(s):

Jia-hua Ding ◽

Zhengping Yu ◽

Bao-an Chen ◽

Yu-feng Li ◽

Bang-he Ding ◽

...

Keyword(s):

Risk Factors ◽

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Cox Regression ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Incidence Rates ◽

Blood Type ◽

Hematopoietic Stem

Abstract Objective To analysis the risk factors for affected patients the long-term persistent survival in 96 patients undergoing Allogeneic Hematopoietic Stem Cell Transplantation, in order to take active prevention and cure measure, and improve trans- plantation curative effect preferably. Methods We retrospectively analysis 96 cases of patients subject to allo-HSCT. The 11 clinical parameters were selected for univariat -e analysis using a Cox regression:age, sex, morbid state, HLA locus, donor type, donor -recipient blood type, conditioning regimen, aGVHD, HC, VOD, IP. Factors that were significant at the 0.1 level on univariate analysis were evaluated by multivariate an- alysis using a Cox regression. The cumulative incidence of aGVHD and patients survival rate were calculated by the method of Kaplan and Meier. Results ninty-five patients achieved sustained donor engraftment except one patients not. The median time of leukocyte engraftment was 13 days. The incidence rates of grades I~IV acute GVHD was 43.75%. grades III~‡WaGVHD was 12.50%. Ten patients relapsed and 38 dead, the overall survival at 5 years was 60.42%. The COX method analysis showed that aGVHD and diease states at transplant were significantly risk factors to improved overall survivals(OS), with relative risk [RR] 2.996 and 2.619, respectively. Conclusion aGVHD and diease states at transplant had significantly improved OS, the key to improvement the outcome 0f allo-HSCT is to reduce the incidence and severity of aGVHD, meanwhile selecting the suitable opportunity for transplantation. We had better do HSCT in CR1to treat that patients with advance refractory and recurrence.

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Monosomal Karyotype in Myeloid Malignancies Is Prognostically Worse Even After Allogeneic Hematopoietc Stem Cell Transplantaion; Results From Two Transplant Centers,

Blood ◽

10.1182/blood.v118.21.4154.4154 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4154-4154 ◽

Cited By ~ 1

Author(s):

Minauchi Koichiro ◽

Akio Shigematsu ◽

Masanobu Nakata ◽

Toshihiro Matsukawa ◽

Koh Ebata ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cox Regression ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Structural Abnormality ◽

Hematopoietic Stem ◽

Myeloid Malignancies ◽

Monosomal Karyotype

Abstract Abstract 4154 Background: Monosomal karyotype (MK) has been defined as the presence of two or more autosomal monosomies or of a single monosomy associated with at least one structural abnormality (Breems et al, JCO 2008). The presence of MK has been associated with extremely poor prognosis in patients with not only acute myeloid leukemia (AML) but myelodysplastic syndrome (MDS) (Patnaik et al, Leukemia 2011). Our goal was to investigate the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies with MK. Patients and methods: We combined data from two transplant centers, Sapporo Hokuyu Hospital and Hokkaido University Hospital, and analyzed consecutive patients who underwent allogeneic transplantation for AML and MDS between January 2003 and July 2010. Patients were divided according to MK classification scheme into four groups (Oran et al, BBMT 2011), CN; cytogenetically normal, MK; monosomal karyotype, CBF; core binding factor abnormalities, Oth (Others); non-CBF and non-MK abnormalities. Patients with acute promyelocytic leukemia were excluded. Resuts: One-hundred eighty three out of 229 patients were analyzed with a median age of 48 years(15–68). Sixty one (33%) were from HLA-matched related donors, 86 (47%) from unrelated and 36 (20%) were cord blood.Conditioning regimens were myeloablative (MAC, n=102, 56%) or reduced intensity(RIC, n=81, 44%). Seventy patients (38%) were cytogenetically normal, 27 (15%)had CBF abnormalities, 70(38%) had non-CBF and non-MK abnormalities and 16(9%) had monosomal karyotype. There was no statistically difference between four groups in age, donor source and conditioning regimen. In the MK group, the proportion of MDS and non-remission state at stem cell transplantation were significantly higher than other groups (p=0.002, p<0.001). Four-year over all survival in patients with MK was 0%, which was significantly inferior to other groups; 50% for CN, 30.4% for CBF, 29.4% for Oth(p<0.001). Cox regression modeling showed that the disease status at stem cell transplantation (p=0.026) and the existence of MK (p=0.012) had prognostic value. Seven of 16 patients with MK died within the first 50 days after transplantation, and 9 patients died within 120 days. Five patients died of infection and 2 died of complicated organ failure and 2 died of progression disease. Three patients who underwent transplantation at non-remission setting, survived more than 1-year experienced chronic graft-versus-host disease, suggesting the existence of GVL effect to myeloid malignancies with MK. Conclusion: This retrospective analysis revealed the dismal prognosis of myeloid malignancies with MK, even after allogeneic HSCT. Novel therapies and strategies are urgently needed for this very poor prognostic group. Disclosures: No relevant conflicts of interest to declare.

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Allogeneic Stem Cell Transplantation - A Long-Term Curative Approach In Patients ≥ 60 Years With Advanced Disease AML/MDS, - The Freiburg Experience Of 250 Consecutive Patients

Blood ◽

10.1182/blood.v122.21.2135.2135 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2135-2135

Author(s):

Hartmut Bertz ◽

Michael Lübbert ◽

Kristin Ohneberg ◽

Ralph Wäsch ◽

Robert Zeiser ◽

...

Keyword(s):

Stem Cell ◽

Prognostic Factors ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Advanced Disease ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Hematopoietic Stem

Abstract Since the introduction of reduced-toxicity conditioning prior to allogeneic hematopoietic stem cell transplantation (alloSCT) we transplanted from 1999 to 2012, 250 consecutive patients (pts) with myeloid malignancies (AML, MDS) aged ≥ 60 years (yrs). The 144 male and 106 female pts with a median age of 66 yrs (range 60-77) were transplanted for de novo AML (n=95), s/tAML (n=104) and MDS (n=51) with 89% unfavorable cytogenetics (CALGB). Since 2004 pts received a prospective fitness assessment (Deschler et al., Haematologica 2013). In 74% the donor was matched/mismatched unrelated and in 26% related. Only 16% were transplanted in CR1/2, 84 % with advanced or untreated disease. The conditioning regimen was the FBM protocol (fludarabine, carmustine, melphalan; Bertz et al., JCO 2003) in 98%, and 97% of the pts received PBSC. For GVHD prophylaxis in 91% a combination of cyclosporine plus alemtuzumab or ATG-F™ was used. At day +30, 94% of the pts had achieved CR by standard measures. With a median follow up of 57 months (3-157) 37% of the pts are alive; main causes of death were relapse (n=62), infection (n=35) and age-related diseases (n=13). The probability of OS/DFS was at 1yr 61%/49%, at 2 yrs 49%/41% and at 5 yrs 37%/34%, respectively. The probability for NRM at 1 yr is 24%. Nineteen known prognostic factors for outcome were evaluated: e.g. patient and donor age, graft size, days between diagnosis and alloHCT, CMV, early/advanced disease, cytogenetics, Sorror and Gratwohl score, donor type, HLA-identity. In the multivariate analysis a better OS (factors with p<0.1; table) was seen with a matched donor; a better DFS with a related donor, and high CD34+ graft content; in contrast, a mismatched donor is a risk factor for reduced DFS.TableMultivariate analysis of prognostic factors* for OS and DFSvariablevalueHazard Ratio95% CI lower limit95% CI upper limitP valueOverall survivalRemission at alloHCTadvanced1.370.862.160.1825HLA mismatchyes1.401.011.960.0463HCT-CI (Sorror)>= 21.311.011.960.1007Peripheral blood blastsyes1.210.841.760.3034Disease-free survivalRemission at alloHCTadvanced1.290.722.300.3946Donorrelated0.640.430.950.0258HLA mismatchyes1.440.992.090.0561CD34+ cells> median0.760.551.040.0867Bone marrow blasts> 5%1.210.781.880.3915*in univariate analysis p<0.157 (AIC criterion; Sauerbrei W, 1999 Applied Statistics,48:313-329.70.) In conclusion, this unique large cohort of older pts with AML/MDS with mainly advanced disease and unfavorable cytogenetics shows a high feasibility, safety and efficacy of alloHCT after the FBM protocol. AML/MDS pts in their 7th and 8th decade of life fit for transplant should be evaluated for alloHCT as very important long-term curative option. Disclosures: No relevant conflicts of interest to declare.

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Prognostic Factors Associated with Outcomes of RIC and MAC Hematopoietic Stem Cell Transplantation: An Indication for the Selection of Conditioning

Blood ◽

10.1182/blood.v112.11.4402.4402 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4402-4402

Author(s):

Tetsuyuki Kiyokawa ◽

Shoichi Nagakura ◽

Michihiro Hidaka ◽

Takahiro Yano ◽

Kazutaka Sunami ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Performance Status ◽

Conditioning Regimen ◽

Albumin Level ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

One Year

Abstract BACKGROUND: Despite recent increase of reduced intensity conditioning (RIC) transplantation, mortality rates after RIC and myeloabrative conditioning (MAC) HSCT remain high and cannot accurately predicted. OBJECTIVE: To determine the value of pre-transplant factors in predicting one year overall survival of allogeneic HSCT with RIC and MAC. Optimizing conditioning selection based on pre-transplant prognostic factors may further improve results of allogeneic HSCT. PATIENTS AND METHODS: A retrospective review of 415 consecutive allogeneic HSCT was performed with attention to mortality and pre-transplant factors in five hematopoietic cell transplantation centers between 2000 and 2005. Patients underwent transplantation from sibling (n=275) or unrelated donors (n=140) with MAC (n=247) or RIC (n=168). Main outcomes and prognostic factors were analyzed in multivariable analyses (a logistic regression model) with RIC and MAC. RESULTS: Mortality before one year occurred in 252 of 415(60.1%) transplant recipients; 137 of 247(55.4%) with MAC and 115 of 168(68.5%) with RIC. Multivariate analysis identified specific and distinct prognostic factors with one year overall survival with MAC (CR/non-CR, performance status, albumin level, creatinine leve and a contain of Ara-C with preconditioning regimens) and with RIC (PS, albumin level, a contain of fuldarabin)(Table). These factors were useful for estimating survival rate of recipient after one year of transplantation (survival estimating equation). CONCLUSION: Our results may provide indication for a better choice of conditioning regimen according to pre-transplant prognostic factors Figure Figure Figure Figure

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The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

Blood ◽

10.1182/blood-2020-136326 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 15-15

Author(s):

Lin Gui ◽

Fei Wang ◽

Jinning Shi ◽

Baoan Chen

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Overall Survival ◽

Multivariate Analysis ◽

Survival Time ◽

Cox Regression ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Rank Test ◽

Newly Diagnosed

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: We retrospectively reviewed the data for 60 multiple myeloma patients who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University from August 2011 to March 2020. According to NLR、MLR、PLR, the patients were divided into the low NLR group (NLR<3.61) or high NLR group (NLR≥3.61), low MLR group (MLR<0.33) or high MLR group (MLR ≥0.33), low PLR group (PLR< 129.78) and high PLR group (PLR ≥129.78). Overall survival time (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of onset was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin, lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR≥129.78、HGB<100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR≥129.78、HGB<100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis. Key Wordsmultiple myeloma; overall survival; NLR; PLR; MLR Disclosures No relevant conflicts of interest to declare.

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Survival of AML Patients Relapsing after Hematopoetic Stem Cell Transplantation: A Single Center Experience

Blood ◽

10.1182/blood-2018-99-118046 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5581-5581

Author(s):

Pelin Aytan ◽

Mahmut Yeral ◽

Aslı Korur ◽

Cigdem Gereklioglu ◽

Funda Tanrıkulu ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Survival Probability ◽

Progressive Disease ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Hematopoietic Stem ◽

Hla Incompatible

Abstract Although it is presumed to be a curative strategy for intermediate and high risk acute myeloid leukemia (AML), many patients relapse after allogeneic hematopoietic stem cell transplantation. This prompt us to examine the ways to improve the outcomes. We retrospectively evaluated 76 AML patients who were transplanted between 2007-2017 years in our clinic. We tried to identify the factors associated with posttransplant relapse, postrelapse survival and if there was a survival benefit of pretransplant consolidation and minimal residual disease (MRD) negativity. We examined the effect of the acute-chronic graft versus host disease (GVHD) and salvage therapy after the posttransplant relapses. The mean age of the patients was 44.6±1.21 years (ranges 21-67). 42.1% were females and 57.9% were males. 43.3% of the patients were in complete remission (CR) MRD positive state before the transplantation whereas 35.5% were in CR MRD negative and 3.9% were in progressive disease state. In 13 patients who were in CR state, the MRD status were not known. 11 (14.5%) patients were considered as in favorable risk, 52 (68.4%) in intermediate risk and 13 (17.1%) in unfavorable risk with respect to cytogenetic analysis before the transplantation. The donors were HLA compatible relatives (77.6%), HLA compatible non-relatives (10.5%), haploidentical people (9.2%), one HLA incompatible relative (1.3%) and one HLA incompatible nonrelative (1.3%). 74 bone marrow transplantations (97.4%) were allogeneic and the remaining two (2.6%) were autologous. Myeloablative conditioning regimen was applied to 57 patients (75%) and 19 patients got (25%) reduced intensity conditioning regimen. GVHD developed in 51.3% after transplantation and 61.5% of these were chronic extensive. Relapse occurred in 27 patients (35.5%), hematological relapse being the most common (31.6%). The median time for the development of relapse was found to be 5.5 months (range: 1.5-37). The overall probability for the development of a relapse was found to be 48.7% (95% CI: 40.9-56.5)(Figure1A). 23 patients (30.3%) died during the study period with a median survival of 9.6 months (range: 1.6-45). In the studied population the overall survival probability was found to be 52.8% (95% CI: 45.4 - 60.2) [Figure 1B]. 36.4%, 28.8% and 30.8% of the patients with favorable, intermediate and unfavorable cytogenetic status died respectively during the study period. The comparison of the survival probability of the patients with favorable, intermediate and unfavorable cytogenetic status was depicted in Figure 2. The overall survival probability of the patients with favorable, intermediate and unfavorable cytogenetic status were 46.6% (95% CI: 26.2-66.9), 54.6% (95 % CI: 45.9 - 63.2) and 36.9 % (95% CI: 25.4 - 48.5) respectively (p=0.807). MRD status of 60 patients were known. At the end of the study period 75.8% of the CR MRD positive and 70.4% of the CR MRD negative patients remained alive. The comparison of the survival of patients in CR with respect to MRD status is shown in Figure 3. The overall survival probability of CR MRD positive patients was 56.3 % (95% CI: 45.3 - 67.3) and this rate was 52.5 % (95% CI: 40.8 - 64.3) in MRD negative patients (p=0.770) [Figure 3]. Patients who developed GVHD had similar overall survival probability with the patients who did not developed the disease; 47.0% vs 57.2%, p=0.115 (Figure 4A). Even the patients with chronic extensive GVHD had similar overall survival rates with the patients who had none or acute GVHD; 49.3 % vs 58.2%, p=0.27 (Figure 4B). 66.7% of the patients with a progressive disease before the transplantation died during the study period and this rate was 27.1% in the patients with CR (p=0.005). In conclusion the overall survival rate of the transplanted AML patients was 52.8% in the study group. The overall survival did not seem to be affected by pre-transplant MRD status, cytogenetic risk factors and administration of consolidation therapy. The only patients who had significantly worse results were the ones who had progressive disease before the transplantation. From this point it would be logical to make transplantation whenever the patient is in first CR regardless of the MRD status and a matched donor is found so that the toxic effects of the consolidation chemotherapy may be prevented. Disclosures No relevant conflicts of interest to declare.

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Prospective analysis of BKV hemorrhagic cystitis in children and adolescents undergoing hematopoietic cell transplantation

Annals of Hematology ◽

10.1007/s00277-021-04454-7 ◽

2021 ◽

Author(s):

Małgorzata Salamonowicz-Bodzioch ◽

Jowita Frączkiewicz ◽

Krzysztof Czyżewski ◽

Olga Zając-Spychała ◽

Ewa Gorczyńska ◽

...

Keyword(s):

Risk Factors ◽

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Hemorrhagic Cystitis ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Significant Risk ◽

Bk Virus ◽

Hematopoietic Cell ◽

Unrelated Donor

AbstractBK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.

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Oral mucositis in patients with acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation in relation to the conditioning used prior to transplantation

Annals of Hematology ◽

10.1007/s00277-021-04568-y ◽

2021 ◽

Author(s):

Aleksandra Wysocka-Słowik ◽

Lidia Gil ◽

Zuzanna Ślebioda ◽

Agnieszka Kręgielczak ◽

Barbara Dorocka-Bobkowska

Keyword(s):

Acute Myeloid Leukemia ◽

Cell Transplantation ◽

Oral Mucositis ◽

Myeloid Leukemia ◽

Hematopoietic Cell Transplantation ◽

Conditioning Regimen ◽

World Health ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Acute Myeloid

AbstractThis study was designed to investigate the frequency and severity of oral mucositis in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, in relation to the type of conditioning used. Eighty patients diagnosed with acute myeloid leukemia were assigned to two groups based on the conditioning regimen used before transplantation. The intensity of oral inflammatory lesions induced by chemotherapy (oral mucositis) was evaluated according to a 5-point scale recommended by World Health Organization. Oral mucosa was investigated in all patients before the transplantation and during two subsequent stages of the post-transplantation procedure in relation to the conditioning regimen used. Mucositis in the oral cavity was observed in the majority of patients (66%) in the first week after transplantation, whereas the largest percentage of patients suffering oral lesions (74%) occurred in the second week after transplantation. A significantly higher percentage of patients with mucositis was observed in the group which underwent myeloablation therapy (74% of MAC and 50% of RIC patients in the first week; 83% of MAC and 53% of RIC patients in the second examination).The severity of mucositis after transplantation was higher in the MAC patients compared to the RIC patients. The highest mean value of the mucositis index was recorded in the second week in the MAC group (1.59). In AML sufferers receiving allo-HSCT, oral mucositis is a significant complication of the transplantation. This condition is more frequent and more severe in patients after treatment with myeloablation therapy.

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Total Body Irradiation for Hematopoietic Stem Cell Transplantation: What Can We Agree on?

Current Oncology ◽

10.3390/curroncol28010089 ◽

2021 ◽

Vol 28 (1) ◽

pp. 903-917

Author(s):

Mitchell Sabloff ◽

Steven Tisseverasinghe ◽

Mustafa Ege Babadagli ◽

Rajiv Samant

Keyword(s):

Cell Transplantation ◽

Total Body Irradiation ◽

Hematopoietic Cell Transplantation ◽

Conditioning Regimen ◽

Late Toxicity ◽

Hepatic Function ◽

Vascular Supply ◽

Entire Body ◽

Hematopoietic Stem ◽

Total Body

Total body irradiation (TBI), used as part of the conditioning regimen prior to allogeneic and autologous hematopoietic cell transplantation, is the delivery of a relatively homogeneous dose of radiation to the entire body. TBI has a dual role, being cytotoxic and immunosuppressive. This allows it to eliminate disease and create “space” in the marrow while also impairing the immune system from rejecting the foreign donor cells being transplanted. Advantages that TBI may have over chemotherapy alone are that it may achieve greater tumour cytotoxicity and better tissue penetration than chemotherapy as its delivery is independent of vascular supply and physiologic barriers such as renal and hepatic function. Therefore, the so-called “sanctuary” sites such as the central nervous system (CNS), testes, and orbits or other sites with limited blood supply are not off-limits to radiation. Nevertheless, TBI is hampered by challenging logistics of administration, coordination between hematology and radiation oncology departments, increased rates of acute treatment-related morbidity and mortality along with late toxicity to other tissues. Newer technologies and a better understanding of the biology and physics of TBI has allowed the field to develop novel delivery systems which may help to deliver radiation more safely while maintaining its efficacy. However, continued research and collaboration are needed to determine the best approaches for the use of TBI in the future.

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Improved outcomes with maintenance therapy after salvage autologous hematopoietic cell transplantation (AHCT) in multiple myeloma: A CIBMTR study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8022 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8022-8022

Author(s):

Oren Pasvolsky ◽

Raphael Fraser ◽

Noel Estrada-Merly ◽

Moshe Yeshurun ◽

Uri Rozovski ◽

...

Keyword(s):

Multiple Myeloma ◽

Maintenance Therapy ◽

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Univariate Analysis ◽

Conditioning Regimen ◽

Hematopoietic Cell ◽

Improved Outcomes ◽

Autologous Hematopoietic Cell Transplantation ◽

Maintenance Group

8022 Background: Maintenance therapy in multiple myeloma (MM) after first autologous hematopoietic cell transplantation (AHCT1) is considered standard of care. Data regarding maintenance therapy after a salvage AHCT (AHCT2) in the setting of relapsed MM are scarce. Therefore, we used data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to examine the use of maintenance therapy after AHCT2 in MM patients and its effect on post-transplant patient outcomes. Methods: We included US adult MM patients who underwent AHCT2 after melphalan conditioning regimen from 2010-2018, and excluded patients who underwent tandem transplants. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Cox proportional hazards models were developed to study the main effect (maintenance use) with other covariates of interest including age, sex, race, performance status, HCT-comorbidity index, MM subtype, stage, creatinine, cytogenetic, conditioning melphalan dose, disease status at transplant, and time from AHCT1 to AHCT2. Results: Of 522 patients, 342 received maintenance therapy and 180 did not after AHCT2. Baseline characteristics were similar between the two groups. Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Common maintenance regimens included immunomodulatory drugs (IMID)-lenalidomide (N = 145, 42%) or pomalidomide (N = 46, 13%) and proteasome inhibitor, bortezomib (N = 45, 13%). Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, p < 0.001, REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)%, p 0.003, PFS 27.8% (22.4-33.5) vs. 9.8% (5.5-15.2), p < 0.001, and OS 54% (47.5-60.5) vs 30.9% (23.2-39.2) p < 0.001, respectively. IMID-containing maintenance regimens were associated with an improved 5-year PFS and OS compared to other maintenance regimens. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis, including NRM: hazard ratio (HR) 0.19 (0.08-0.44), p 0.0001, REL: HR 0.58 (0.47-0.72), p < 0.0001, PFS HR 0.52 (0.43-0.64), p < 0.0001, and OS HR 0.46 (0.36-0.60), p < 0.0001. We conducted additional analyses to investigate a possible selection bias in the maintenance group including landmark analysis at 100-days and 6-months post-AHCT2 as well as a subgroup analysis of patients who received melphalan 200mg/m2 as conditioning for AHCT2 (as a surrogate for fitness)- all these analyses also showed improved outcomes in the maintenance group. Second cancers were reported in 17 (5%) patients in the maintenance group and 6 (3%) patients and no-maintenance group (p 0.39). Conclusions: Maintenance therapy after AHCT2 is associated with superior outcomes in MM patients.

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