Allogeneic hematopoietic cell transplantation for myelofibrosis (MF) in high risk patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7062-7062
Author(s):  
Swapna Narayana ◽  
Saurabh Chhabra ◽  
Ravi Kishore Narra ◽  
Aniko Szabo ◽  
Mehdi Hamadani ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Rank Test ◽  
Survival Outcomes ◽  
Unrelated Donor ◽  
Jak2 Mutation ◽  
Medical College ◽  
Kaplan Meier

7062 Background: Although allogeneic transplantation(alloHCT) is the only curative treatment modality for MF, given the median age of MF, most patients are not candidates for alloHCT due to concerns for treatment-related mortality(TRM), age and comorbidities. Methods: We reviewed the outcomes of 24 recipients of matched related/unrelated donor alloHCT for MF at the Medical College of Wisconsin. All patients with JAK2 mutation(62%) and/or constitutional symptoms recieved Roxulitinib atleast 4 months prior to alloHCT with discontinuation of Ruxolitinib 48 hrs prior to the start of conditioning. Majority(91%) received conditioning with Fludarabine and Busulfan(Flu/Bu4, Flu/Bu3,Flu/Bu4). Only 2 patients received TBI based regimen; Flu/TBI(2-4Gy). Those with splenomegaly > 22cm received pre-transplant splenic radiation(n = 11;49%). Survival outcomes were analyzed using Kaplan-Meier curves and compared between groups using log-rank test. Results: Median age was 57 years(range,40-67) with 29% > 60 years. A 46% had primary ET or PV that evolved to MF and 17% had MDS cytogenetics. Majority(74%) patients MF-3 grade. More than 80% recieved Ruxolitinib and 25% were treated with hypomethylating/cytotoxic chemotherapy. HCT-CI score was≥3 in 62%. Four patients had cirrhosis and portal hypertension(PHTN), and another 3 had PHTN without Cirrhosis.At median follow up of 36months, 3-year overall survival(OS) and relapse-free survival were(RFS) 70%. Marrow fibrosis improved post HCT with only 15% grade 3. One patient relapsed and died from AML 15 months post-HCT. TRM was 25% at 3 years; causes of death were sepsis(n = 3), alveolar hemorrhage(n = 1) and myocardial infarction(n = 1). Variables such as type of donor, DIPSS scoring, MF grade and age of the patient were not significantly associated with OS/RFS on univariate analysis. Conclusions: Despite advanced age and 62% with HCT CI≥3, we report excellent survival outcomes compared to other prior data. Careful patient selection, use of Ruxolitinib pre-HCT, splenic irradiation pre-HCT and Flu/Bu based conditioning regimen all contributed to the remarkable results in this series.

Busulfan and Fludarabine Conditioning Regimen Negates the Impact of Comorbidity Score on Nonrelapse Mortality in Patients with AML/MDS

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 799-799
Author(s):  
Uday Popat ◽  
Rima Saliba ◽  
Leandro de Padua Silva ◽  
Borje S Andersson ◽  
Amin M Alousi ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Unrelated Donor ◽  
Comorbidity Score ◽  
Cart Analysis ◽  
Reduced Toxicity ◽  
The Impact ◽  
Primary Predictor

Abstract BACKGROUND: Comorbidities as measured by newly developed Hematopoietic cell transplantation specific comorbidity index (HCT-CI) increases non relapse mortality in patients with hematological malignancies undergoing allogeneic transplantation. Whether this applies to recently treated patients with newer reduced toxicity regimens is not known. To evaluate this, we studied the factors influencing non relapse mortality in patients with AML/MDS. METHODS: 840 consecutive patients with AML/MDS undergoing allogeneic transplantation between January 1996 and April 2008 from a matched related or unrelated donor at our institution were studied. Information about disease characteristics, treatment, and outcomes was prospectively recorded in the departmental database. Comorbidities were retrospectively scored as previously described (Sorror et al Blood106: 2912–2919, 2005). Predictors of non-relapse mortality(NRM) at 2 years post SCT were evaluated on univariate analysis using Cox’s proportional hazards model and included age, sex, disease status at transplant, donor type, graft type, conditioning regimen (reduced intensity, ablative IV Busulfan(Bu) and Fludarabine(Flu), all other ablative regimens), and HCT-CI comorbidity score. Factors significant at the 0.1 level on univariate analysis were considered for classification and regression tree analysis (CART) to adjust for confounding and interaction effects. Statistical significance was defined at the 0.05 level, and cells including less than 10 patients were considered terminal in the CART analysis. RESULTS: There were 470(56%) males and 370(44%) females with a median age of 50 (range 18–77) years. 21% of patients were older than 60 years. HCT-CI comorbidity scores were as follows: 0 in 16% of patients, 1 in 13%, 2 in 13%, 3 or more in 58%. Donors were matched related for 58% of patients and unrelated for 42%. At the time of transplant, 22% of patients were in first complete remission (CR), 15% in second or third CR, and 63% had active disease. 36% of patients had reduced intensity conditioning regimen; 39% had myeloablative regimen consisting of Flu and Bu, and the remaining 25% had other myeloablative regimens. Cumulative incidence of NRM at 2 years was 26% (23–30). Univariate analysis showed that age > 60 (HR 1.6; p 0.002), disease status beyond first complete remission (HR 2.7; p <0.001), matched unrelated donor (HR 1.6; p 0.001), regimen other than Flu/Bu (HR 2.6; p<0.001), and a comorbidity score greater than 2 (HR 1.4; p 0.03) were associated with higher NRM. CART analysis (fig) showed that the use of Flu/Bu conditioning was the primary predictor of lower NRM. Age older than 60 years was the only additional significant predictor of NRM in patients who received Flu/Bu (HR 3.1; p 0.01). In patients who did not receive Flu/Bu, disease status at transplantation was the primary predictor of NRM with CR1 patients having a significantly lower incidence of NRM (CI =16%). The impact of donor type was only significant in patients who were not in CR1 with recipients of a matched related graft having a significantly lower NRM (CI=29%) than recipients of a matched unrelated graft (CI=46%). Comorbidity score did not significantly predict outcome in this analysis. CONCLUSION: Flu/Bu, a fully ablative reduced toxicity conditioning regimen, results in very low NRM, nullifying the impact of comorbidities. Figure Figure

scholarly journals Survival outcomes and prognostic factors for ascending nasopharyngeal carcinoma (T4N0-1) receiving radiation therapy combined with chemotherapy: a population-based study from SEER database.

2020 ◽  
Author(s):  
Fangzheng Wang ◽  
Jiang Chuner ◽  
Piao Yongfeng ◽  
Wang Lei ◽  
Yan Fengqin ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Prognostic Factors ◽  
Nasopharyngeal Carcinoma ◽  
Univariate Analysis ◽  
Population Based ◽  
Rank Test ◽  
Survival Outcomes ◽  
Cancer Specific Survival ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Models

Abstract Purpose This study aims to investigate survival outcomes and prognostic factors for upward nasopharyngeal carcinoma (NPC) patients receiving radiation therapy (RT) combined with chemotherapy (CT). Methods A total of 421 previously untreated, newly diagnosed T4N0-1 NPC patients, who were identified within the Surveillance, Epidemiology, and End Results (SEER) registry (years 2004–2015), were collected and retrospectively reviewed. All patients received treatment of RT and CT. Kaplan-Meier analysis was used to evaluate overall survival (OS) and cancer-specific survival (CSS). The differences in OS and CSS were compared using Log-rank test. The independent prognostic factors were established by using univariate and multivariate Cox proportional hazard models. Results With a median follow-up duration of 37 months (range: 3-154 months), the 5-year estimate OS and CSS rates were 59.3% and 63.7%, respectively. N0 and ≥ 65 years were poor prognostic factors for OS and CSS. Moreover, histology and race were associated with OS and CSS. Univariate analysis indicated that ≥ 65 years, N0, NHB and grade III were unfavorable independent prognosticators of OS and CSS. Multivariate analysis demonstrated that ≥ 65 years, N0 and NHB were correlated with poor OS and CSS. Conclusion Patients with stage T4N0-1 NPC receiving RT plus CT had favorable OS and CSS. Moreover, age, N stage and race were independent prognostic factors of OS and CSS.

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

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.

scholarly journals Cohort study of the overall survival of patients with pancreatic cancer in a hospital of specialties of Quito-Ecuador in the period 2007–2017

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cohort Study ◽  
Survival Time ◽  
Univariate Analysis ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Icd 10 ◽  
The Difference ◽  
Clinical Records

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.

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

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.

scholarly journals Investigation of donor KIR content and matching in children undergoing hematopoietic cell transplantation for acute leukemia

2020 ◽  
Vol 4 (7) ◽  
pp. 1350-1356 ◽  
Author(s):  
Michael R. Verneris ◽  
Jeffrey S. Miller ◽  
Katherine C. Hsu ◽  
Tao Wang ◽  
Jennifer A. Sees ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Cox Regression ◽  
Pediatric Population ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Unrelated Donor ◽  
Entire Cohort

Abstract Multiple models of donor killer immunoglobulin receptor (KIR) alloreactivity or KIR genotype have been reported to be protective against leukemia relapse after allogeneic transplantation. However, few studies have addressed this topic in the pediatric population. Here, we assessed the outcomes of allogeneic transplantation in children with acute lymphoblastic leukemia (ALL; n = 372) or acute myeloid leukemia (AML; n = 344) who received unrelated donor (URD) transplantation and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 2005 to 2016. As expected in this pediatric population, most patients underwent myeloablative conditioning while in remission and with bone marrow as a stem cell source. We tested KIR ligand mismatch, KIR gene content (centromeric [Cen] B), KIR2DS1 mismatching, and Cen B/telomeric A using Cox regression models and found that none were significantly associated with either relapse or disease-free survival when considering the entire cohort of patients (ALL and AML), AML, or ALL separately. Moreover, there was no significant association with outcomes in the in vivo T-cell–depleted (ie, serotherapy) cohort. This study, which is the largest analysis of donor KIR in the pediatric acute leukemia population, does not support the use of KIR in the selection of URDs for children undergoing T-replete transplantation.

Non-ocular melanomas in cats: a retrospective study of 30 cases

2016 ◽  
Vol 19 (4) ◽  
pp. 351-357 ◽  
Author(s):  
Gabriel Chamel ◽  
Jérôme Abadie ◽  
Olivier Albaric ◽  
Sophie Labrut ◽  
Frédérique Ponce ◽  
...  
Keyword(s):  
Mitotic Index ◽  
Primary Tumour ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinical Signs ◽  
Surgical Margins ◽  
Rank Test ◽  
Kaplan Meier ◽  
Product Limit ◽  
Junctional Activity

Objectives The aim of the study was to describe the clinical outcome of 30 cats with non-ocular melanomas and to evaluate the association between clinical or pathological parameters and overall survival time. Methods The database of the animal histopathological laboratory of the National Veterinary School of Nantes (Oniris, Nantes, France) was retrospectively searched to identify cases of feline non-ocular melanomas between December 2009 and April 2014. For each case, clinical data, including signalment, location of the primary tumour, staging, treatment and outcome, were collected from the medical records or via interviews with referring veterinarians. Histological and immunohistochemical evaluation included mitotic index, cytonuclear atypias, junctional activity, Melan A and S100 immunostaining, and surgical margins. Univariate analysis to test the prognostic value of the different variables was performed by the Kaplan–Meier product limit method using the log-rank test of significance. Results Thirty cats were included in the study. Eleven had a cutaneous non-auricular melanoma, six had a tumour located on the pinna and 13 had a tumour in the oral cavity. Cats with auricular melanomas were significantly younger than cats with tumours in other locations. Location and presence of clinical signs were not of prognostic significance, but the achromic phenotype was significantly associated with a poorer prognosis. Twenty cats were treated with surgery and survived significantly longer than cats that received only medical treatment or that did not receive any treatment. According to our data, mitotic index, cytonuclear atypias, junctional activity, Melan A or S100 expression, and surgical margins were not associated with survival. Conclusions and relevance We show for the first time, in a large series, that the auricular form of melanoma affected significantly younger cats than other extraocular forms. Most feline non-ocular melanomas are malignant and achromic tumours are associated with a poorer prognosis. According to this study, surgery should be considered as a priority.

Allogeneic Hematopoietic Cell Transplantation (allo-HCT) Can Induce Durable Remission in Heavily Pretreated Relapsed Hodgkin Lymphoma. (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1192-1192
Author(s):  
Robert Chen ◽  
Joycelynne Palmer ◽  
Leslie Popplewell ◽  
Jessica Shen ◽  
Eileen Smith ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Heavily Pretreated

Abstract Abstract 1192 Poster Board I-214 Background: Even though Hodgkin lymphoma (HL) is a curable disease, about, 20-30% patients are either refractory to induction chemotherapy or relapse post treatment. High dose chemotherapy and autologous HCT has been shown to be an effective salvage therapy for patients with relapsed HL. However, relapse continues to occur after auto-HCT, especially in patients with chemoresistant or poor-risk features at relapse. The prognosis of these patients is poor with limited options of treatment. Although allo-HCT offers both cytoreduction and potential graft-versus-tumor effect, its use in relapsed HL has been limited by non-relapse mortality (NRM) and patient co-morbidities induced by numerous prior treatments. To examine the potential impact of allo-HCT on survival and disease outcomes, we performed retrospective analysis of allo-HCT in relapsed/refractory HL to determine if allo-HCT can induce long-term remission in heavily pretreated relapsed HL. Results: Between January 2003 and December 2008, 29 patients with relapsed HL underwent allo-HCT at City of Hope National Medical Center. The median age was 37 (range: 14-63). 20 (69%) patients were chemosensitive at time of allo-HCT. 17 (59%) patients had prior auto-HCT. 16 (55%) patients received matched siblings and 13 (45%) received unrelated donor cells. 20 (69%) patients had prior radiation treatments. The median number of prior regimens was 5 (range: 2-8). 23 (79%) patients underwent a non-myeloablative conditioning regimen while 6 (21%) patients had a myeloablative regimen. 14 (48%) patients received Tacrolimus/Sirolimus as graft versus host disease prophylaxis and 15 (52%) patients received a combination of Cellcept/CsA, Cellcept/CsA/MTX, Tacrolimus/MTX, or Tacrolimus/Sirolimus/MTX. With a median follow up of 31.9 months (range: 9.7-69.1) for surviving patients, the results show: Conclusion: Allogeneic hematopoietic cell transplantation in heavily pretreated relapsed Hodgkin's lymphoma is feasible, tolerable, and can induce durable clinical remissions. Disclosures: No relevant conflicts of interest to declare.

Busulfan Dosing May Affect Survival Following Reduced Intensity Stem Cell Transplantation in Patients with Acute Myelogeneous Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4328-4328
Author(s):  
Karen K Ballen ◽  
Steven L McAfee ◽  
Bimalangshu R Dey ◽  
Christine Dube ◽  
Eyal C Attar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Total Dose ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Unrelated Donor ◽  
Gvhd Prophylaxis ◽  
Acute Myelogeneous Leukemia ◽  
Reduced Intensity

Abstract Abstract 4328 The prognosis for patients with acute myelogeneous leukemia over age 60 is poor, with a 5 year survival of less than 10%. Reduced intensity allogeneic transplantation has been employed in an attempt to improve survival. We report 23 patients who received reduced intensity allogeneic transplantation after a conditioning regimen of busulfan and fludarabine. Fifteen patients received a transplant from a matched sibling donor,1 patient from a 5/6 matched child and 7 patients from a fully matched (10/10) unrelated donor. We treated 10 patients with the reduced intensity conditioning regimen of busulfan IV 0.8 mg/kg daily Days -6, -5, -4, -3 (total dose 3.2 mg/kg) and fludarabine IV 30 mg/m2 Days -6,-5, -4, -3 (total dose 120mg/kg). After November, 2007, 10 patients were treated with twice daily busulfan IV 0.8mg/kg (total dose 6.4 mg/kg) with the same dose of fludarabine. Three patients were treated on a national protocol in which the same dose of busulfan (6. 4 mg/kg) was administered but given at 0.8 mg/kg four times daily for 2 days on Days -4 and -3 with fludarabine. GVHD prophylaxis was cyclosporine or tacrolimus with either cellcept or (after July, 2008) methotrexate. Seven recipients of unrelated donor or mismatched transplants also received rabbit antithymocyte globulin 1.5 mg/kg Days -3, -2, -1 (total dose 4.5 mg/kg) as part of their GVHD prophylaxis. Median age was 65 years (range 46-70 years). Fourteen patients were in 1st complete remission, 8 were in 2nd complete remission, and one patient had active disease at the time of transplant. Two patients had received a prior autologous stem cell transplant and 2 patients had received a prior allogeneic transplant. The median days to neutrophil (ANC >500) and platelet engraftment (plt >20K) were 15 and 14 respectively. The median length of stay was 25 days (range 13-40 days). Median follow-up was 12 months among the 10 patients still alive. The incidence of acute GVHD Grades II-IV and chronic GVHD were 44% and 35% respectively. Transplant related (non relapse) mortality at 100 days and at 6 months was 0. The overall non-relapse mortality was 4%. Relapse rate was 67% in the daily busulfan group and 46% in the higher dose busulfan group. The one-year overall and disease-free survivals for all patients were 44% and 25% respectively. Causes of death were relapse in 12 patients and in one patient sepsis six years after transplant. In multivariate analysis, disease status, age, and GVHD did not predict for survival, perhaps due to the small sample size. There was a trend to improved survival in the higher dose busulfan group but the follow up was shorter for these patients. In summary, 1) Reduced intensity transplantation is tolerated well in an older population with acute myelogeneous leukemia, with no transplant related mortality at Day 100 or at 6 months post transplant; 2) Relapse rermains the most common cause of death; 3) There was a trend to improved survival with a twice daily busulfan dosing. Future studies will address the outcomes of twice daily busulfan dosing in a larger cohort of older patients with AML in complete remission. Disclosures: Spitzer: Genzyme: Consultancy.

A Randomized 3-Arm Phase II Study to Determine the Most Promising Postgrafting Immunosuppression for Prevention of Acute Graft-Versus-Host Disease (GVHD) After Unrelated Donor Hematopoietic Cell Transplantation (HCT) Using Nonmyeloablative Conditioning for Patients with Hematologic Malignancies: A Multi-Center Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 348-348 ◽  
Author(s):  
Brenda M. Sandmaier ◽  
Michael Maris ◽  
Barry Storer ◽  
Lars Vindelov ◽  
Amelia Langston ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Phase Ii ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Sequential Trials

Abstract Abstract 348 We previously reported results of 3 sequential trials of GVHD prophylaxis with mycophenolate mofetil (MMF) BID/TID and cyclosporine (CSP) BID with various taper schedules in patients (pts) with advanced hematologic malignancies given unrelated G-CSF-mobilized peripheral blood stem cell (PBSC) grafts after fludarabine 90 mg/m2 and 2 Gray total body irradiation. Cumulative incidences of grades II-IV acute GVHD in the 3 trials were 52, 53 and 77%, respectively. The goal of the current protocol was to evaluate, in a phase II randomized 3-arm study, which drug combination or schedule was most promising in preventing acute GVHD. Tacrolimus (Tac) was used in place of CSP and each of the 3 arms used MMF TID until day 30 and then BID, but the subsequent duration of MMF varied. In Arm1, pts received Tac until day 180 and MMF until day 96. In Arm2, Tac was given until day 150 and MMF until day 180. In Arm3, Tac was given until day 150 and MMF until day 180 with the addition of rapamycin from days -3 through 80. One hundred seventy-five pts ineligible for myeloablative conditioning were enrolled on this multi-institutional study between Jan/05 and Aug/09, and results on the first 159 pts (Arm1 n=56; Arm2 n=51; Arm3 n=52) are reported here with a median follow-up of 18.4 months for surviving pts. The median age of pts was 60 (range 13-75) yrs. Sixty-six (42%) had previous autologous (n=55) or allogeneic (n=11) HCT. All pts were matched for HLA-DRB1 and -DQB1 at the allele level: 16 had single allele mismatches at HLA-A, -B or –C and the remainder (n=143) were fully HLA-matched. Diagnoses included AML (n=72), NHL (n=36), MM (n=19), ALL (n=10), CLL (n=9), MDS (n=8), HL (n=4), and CML (n=1). Randomization was based upon transplant center (FHCRC vs other), number of prior chemotherapy treatments (0-2 vs 3+), and age (<55 vs 55+ years). The pts received PBSC grafts containing a median of 7.9 ×106 CD34 and 2.8 × 108 CD3 cells/kg. Sustained donor engraftment occurred in 99.4% of pts. The day-150 cumulative incidences of grades II-IV (figure 1) and III-IV acute GVHD were as follows: Arm1: 56%, 9%; Arm2: 52%, 12%; and Arm3: 45%, 10%, respectively. Chronic GVHD requiring therapy was as follows: Arm1: 44%, Arm2: 35%, and Arm3: 55% of pts. The 6-month nonrelapse mortality was 6% in Arm1, 8% in Arm2, and 2% Arm3. The 2-year Kaplan-Meier estimates of relapse and nonrelapse mortality (figure 2) were as follows: Arm1: 27%, 24%; Arm2: 39%, 19%; and Arm3: 30%, 15%, respectively (overall 32% and 20%, respectively). The 2-year overall and progression-free survivals were as follows: Arm1: 49%, 41%; Arm2: 42%, 37%; Arm3: 55%, 41%, respectively (overall 48% and 40%, respectively). The addition of rapamycin to MMF and Tac (Arm3) resulted in the lowest incidence of grades II-IV acute GVHD (p=0.09 compared to reference Arm1), without a significant difference in chronic GVHD. While the phase II design of the study was not powered to show statistical differences between the 3 arms, the lower incidence of grades II-IV acute GVHD combined with the low morbidity and nonrelapse mortality in Arm3 using MMF, Tac and rapamycin is encouraging and warrants further study. Disclosures: Off Label Use: Fludarabine - conditioning prior to HCT. Mycophenolate mofetil - immunosuppression after HCT. Tacrolimus - immunosuppression after HCT. Rapamycin - immunosuppression after HCT..

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