Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia Transformed from Myelofibrosis

Abstract Background and Rationale: Transformation of myelofibrosis (MF) to acute leukemia (>20% blasts) portends a grave prognosis. Allogeneic stem cell transplantation (ASCT) is a curative approach for patients with acute leukemia; however, the outcomes of ASCT in patients with MF transformed to acute leukemia are currently unknown. Methods: Fifty-one consecutive patients with either primary (PMF) or secondary (SMF) were transplanted at UTMDACC after 1994. Thirteen patients who developed AML (25%), 10 arising from PMF and 3 with SMF, received an ASCT from a sibling or matched unrelated donor. Median age was 59 years. Five patients (38%) had prior splenectomy. JAK2V617F mutation analysis was performed in 7, and was present in 5 patients. Cytogenetics were intermediate in 10 and poor-risk in 3 patients. Seven patients (54%) were not in remission at the time of transplant. Eleven of 13 patients received induction chemotherapy; 6 achieved remission, while 7 had persistent disease at the time of transplant. One patient had a prior autologous transplant and 2 patients had prior allogeneic transplant for myelofibrosis. The donors were matched siblings (7 patients), matched unrelated (4 patients) and 1 antigen mismatched relatives (2 patients). The stem cell source was peripheral blood in 9 and bone marrow in 4 patients. Nine patients received a reduced-intensity conditioning regimen with a fludrabine-melphalan-based regimen, and 4 myeloablative conditioning (3 fludarabine-busulfan, 1 busulfan-cyclophosphamide). Results: All patients engrafted, 75% achieved full donor chimerism, on day 30. Neutrophil and platelet engraftment occurred after a median of 13 and 21.5 days. Twelve evaluable patients achieved remission; 3 subsequently relapsed. JAK2V617F mutation became negative after transplant in all tested patients and reappeared in 1 patient who later relapsed. Grade 2–4 aGVHD developed in 3 patients (grade 3–4 in one) and cGVHD in 4/11 evaluable patients (extensive in two). After a median follow-up of 17.2 months (range 7.2–128.6 mo), OS and EFS were 49% (SE 15%) and 44% (SE 14%), respectively (Figure1). Six patients died, related to disease relapse (2), pneumonia (2), GVHD (1), and hepatic failure (1). Conclusion: Patients with acute leukemia transformed from myelofibrosis with good performance status can achieve durable complete remissions with ASCT. Figure 1. Overall survival (continuous line) and disease-free survival (interrupted line) in 13 patients with acute leukemia transformed from MF post ASCT after a median follow-up of 17.2 months. Figure 1. Overall survival (continuous line) and disease-free survival (interrupted line) in 13 patients with acute leukemia transformed from MF post ASCT after a median follow-up of 17.2 months.

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Allogeneic Stem Cell Transplantation for Multiple Myeloma: a Single Center Experience

Blood ◽

10.1182/blood.v128.22.5874.5874 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5874-5874 ◽

Cited By ~ 1

Author(s):

Amarilis Figueiredo ◽

Harold Atkins ◽

Natasha Kekre ◽

Andrea Kew ◽

Arleigh McCurdy

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Disease Free Survival ◽

Myeloablative Conditioning ◽

Free Survival ◽

Related Donor ◽

Disease Free

Abstract Introduction The use of allogeneic stem cell transplantation (Allo-SCT) in patients with multiple myeloma (MM) remains controversial, but it offers prolonged disease free survival in some patients. It is unclear which patients should undergo Allo-SCT, what conditioning regimen should be used, and what the timing of the transplant should be in the course of the disease. Therefore, we sought to contribute our center's experience to the growing body of literature. Methods We performed a retrospective observational cohort study of all patients who underwent Allo-SCT for multiple myeloma at our center between January 1, 1992 and May 31, 2016. Categorical variables were compared using Pearson's chi-square test and the Kaplan-Meier method was used for the overall survival curves. Results Thirty-four patients underwent Allo-SCT for multiple myeloma and were included in this analysis. The median age was 40 years and 21 (62%) were male. Nineteen patients (56%) underwent Allo-SCT as upfront therapy, 1 (3%) underwent tandem autologous stem cell transplant (auto-SCT) followed by Allo-SCT, and 14 (41%) had salvage Allo-SCT at the time of relapse. Twenty-four (70.5%) patients had a matched related donor, 1 (3%) had a mis-matched related donor, 8 (23.5%) had matched unrelated donor and matching in 1 (3%) was not available. Myeloablative conditioning was given in 18 patients (52.9%) and non-myeloablative conditioning in 13 (38.2%) with 3 (8.8%) missing. The conditioning regimens included: 5 (15%) Flu-Mel, 7(20.6%) Flu-Bu, 13 (38%) Bu-Cy ± TBI, 6 (17.6%) MelVPTBI, and 3 (8.8%) were missing. Median overall survival (OS) for all patients was 72.5 months from diagnosis (figure 1) and 26.5 months from the time of Allo-SCT. For the 19 patients who had upfront Allo-SCT, median OS from diagnosis was 7.4 years compared to 5.3 years for those having salvage Allo-SCT (figure 2). However, in the upfront group 6 (32%) were alive 10 years post Allo-SCT and the survival curve reaches plateau, whereas in the salvage group, no patient was alive after 8 years post Allo-SCT. There was no difference in median survival between myeloablative and non myeloablative conditioning (2.9 versus 1.33 years, p=0.925). There have been 20 deaths in our cohort (59%); 5 (14.7%) from transplant related mortality within 1 year, 9 (26.5%) from disease progression, and 6 (17.6%) transplanted remotely whose cause of death is unknown. Conclusions Our data suggest that Allo-SCT offers prolonged disease free survival in some patients. In our small cohort, a greater proportion of patients undergoing upfront Allo-SCT achieved long term survival, raising the possibility that this group of patients may benefit more from Allo-SCT. Further prospective studies are needed to clarify the role of Allo-SCT in MM. Disclosures Kew: Celgene: Honoraria. McCurdy:Celgene: Honoraria.

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Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATCL): A Retrospective Study of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v118.21.3115.3115 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3115-3115

Author(s):

Esa Jantunen ◽

Ariane Boumendil ◽

Alessandro Rambaldi ◽

Marc Schapira ◽

Jian Jian Luan ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cell Lymphoma ◽

Disease Free Survival ◽

Free Survival ◽

History Of ◽

Disease Free

Abstract Abstract 3115 Background: EATCL is a rare subtype of peripheral T-cell lymphoma frequently observed in patients with a history of celiac disease. EATCL is characterized by poor prognosis when treated with conventional chemotherapy with only 10–20 % of long-term survivors. Limited data are available on feasibility and efficacy of stem cell transplantation in this lymphoma entity. Patients and methods: The database of the EBMT was used to identify patients with EATCL who had received autologous and/or allogeneic stem cell transplantation in 2000–2007. All centres reporting these patients were contacted to receive confirmation to histopathology report/pathology review and to obtain information in regard to treatment prior to stem cell transplantation and more recent follow-up data. Results: Altogether 85 patients with EATCL were identified. Seventy-three patients had received ASCT and 12 patients allogeneic SCT. Histological report/review with additional follow-up data was available from 22 ASCT treated patients which are reported here. There were 14 females (64 %) and eight males with a median age of 55 years at the time of transplant. Half of the patients had a history of coeliac disease. The median number of treatment lines before ASCT was 1 and 50 % of the patients were in the first remission at the time of ASCT. BEAM was the most commonly used high-dose regimen (17 pts, 77 %) and all patents received blood stem cell grafts. The median time from the diagnosis to ASCT was 6 months. The median follow-up time for living patients was 45 months from ASCT. During the follow-up relapse has been observed in 13 patients (59 %), the median time was only four months from ASCT. The median disease-free survival and overall survival were nine months and 15 months, respectively. Two-year overall survival, disease-free survival, cumulative incidence of relapse and non-relase mortality (NRM) was 45%, 40%, 55% and 4%, respectively. Conclusions: ASCT is feasible in selected patients with EATCL with a low NRM. Of transplanted patients 40 % remained disease-free beyond 2 years. This seems to be superior when compared to historical experiences although selection factors should be taken into account. ASCT is a treatment option in transplant eligible EATCL patients who respond to initial therapy. Disclosures: No relevant conflicts of interest to declare.

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Impact of Molecular Genetics on Disease-Free Survival in Myelofibrosis Patients Following Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood.v126.23.352.352 ◽

2015 ◽

Vol 126 (23) ◽

pp. 352-352 ◽

Cited By ~ 2

Author(s):

Nicolaus Kroeger ◽

Victoria Panagiota ◽

Tatjana Zabelina ◽

Michelle Maria Araujo Cruz ◽

Rabia Shahswar ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Molecular Genetics ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Univariate Analysis ◽

Disease Free Survival ◽

Free Survival ◽

Disease Free

Abstract Introduction Primary or post-ET/post-PV myelofibrosis is one of the Philadelphia chromosome-negative chronic myeloproliferative neoplasia characterized by significantly reduced overall survival. More recently several mutated genes have been detected, which allow, in addition to clinical factors, to identify patients with a significantly shorter overall survival and a higher risk of transformation into acute leukemia. Allogeneic stem cell transplantation is still the only curative treatment option for patients with myelofibrosis, and due to the inherent risk of the treatment procedure careful selection of the patients is required. Molecular genetics may help to select patients for allogeneic stem cell transplantation. Patients and methods To determine the impact of mutated genes in patients with myelofibrosis who underwent allogeneic stem cell transplantation we analyzed samples from 169 patients with a median age of 58 years (r: 18 - 75) who received allogeneic stem cell transplantation either from related (n = 36) or unrelated (n = 133) donor. Stem cell source were more often peripheral blood stem cells (n = 165) than bone marrow (n = 4). The intensity of conditioning was mainly reduced intensity (n = 166), rather than myeloablative conditioning (n = 3). Patients suffered from primary myelofibrosis (n = 110), post-ET/PV myelofibrosis (n = 46), while 13 patients were in acceleration or had transformed into acute myeloid leukemia. According to dynamic IPSS (DIPSS) (n = 165) the patients were either low (n = 7), intermediate-1 (n = 35), intermediat-2 (n = 91), or high risk (n = 32). Regarding molecular genetics we found JAK2V617F mutations in 62%, calreticulin (CALR) mutations in 20%, MPL mutations in 4%, U2AF1 in 7%, SRSF2 in 10%, SF3B1 in 4%, ASXL1 in 29%, IDH1 in 2%, IDH2 in 3%, CBL in 1%, DNMT3A in 4%, TET2 in 10%, EZH2 in 4%, while none of the patients showed mutations in ETV6 and PTPN11. Overall, only in 11 patients no mutation could be detected. One mutation could be detected in 41%, 2 mutations in 30%, 3 mutations in 11%, 4 mutations in 5%. Results During follow-up 39 patients experienced relapse and 46 patients experienced non-relapse mortality. From the non-molecular factors regarding disease-free survival in univariate analysis age < 58 (p < 0.01), intermediate-1 and low risk according to DIPPS (p = 0.002), HLA-matched vs. mismatched (p = 0.04) were significant factors for improved disease-free survival. Regarding molecular markers improved disease-free survival was seen for patients with mutations in CALR (p = 0.005), while negative impact on disease-free survival was seen for mutations in U2AF1 (p = 0.035), ASXL1 (p = 0.05), IDH2 (p = 0.006), DNMT3A (p = 0.029). No significant difference could be seen for patients with EZH2, IDH1, SRSF2, and SF3B1 mutations. There was no difference in disease-free survival for patients without any mutation vs. 1, and more than 1 mutation (p = 0.12). Regarding the previously described unfavorable mutations ASXL1, SRSF2, EZH2, IDH1, and IDH2, we found 40 patients who had at least 1 of these unfavorable mutations, 11 had 2 of these mutation, and 1 had 3 of these unfavorable mutations. However, the estimated 5-year disease-free survival did not differ significantly between patients without any of these unfavorable mutations, with 1 or with 2 of them (47 vs. 40 vs. 41%, p = 0.5). Conclusions These results suggest that some molecular marker such as ASXL1, U2AF1, IDH2 and DNMT3A negatively influence DFS in myelofibrosis after allogeneic stem cell transplantation in a univariate analysis. In contrast, the poor prognosis of the recently described unfavorable mutated genes SRSF2, EZH2, and IDH1 was not observed and may therefore be overcome by allogeneic stem cell transplantation. Disclosures No relevant conflicts of interest to declare.

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Improved Disease Survival without Increased GVHD Using Low Dose Cyclosporine and Prednisone in Allogeneic Stem Cell Transplantation - a Case Control Study.

Blood ◽

10.1182/blood.v104.11.5148.5148 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5148-5148

Author(s):

John J. Moore ◽

David D. Ma ◽

Tony Dodds ◽

Sam Milliken ◽

Keith Fay ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Survival Benefit ◽

Low Dose ◽

Disease Free Survival ◽

Prophylactic Regimen ◽

Free Survival ◽

Allogeneic Hsct ◽

Disease Free

Abstract Allogeneic stem cell transplantation (HSCT) can cure numerous malignant and non-malignant diseases but this is offset by significant morbidity and mortality from graft versus host disease (GVHD). The standard prophylactic regimen contains cyclosporine, methotrexate and/or prednisone however doses and the timing of tapering remain unclear. Recently Ruutu et al demonstrated reduced GVHD using a prednisone based prophylactic regimen without a survival benefit whereas Baclgalupo et al demonstrated an increased survival benefit with 1mg/kg cyclosporine over 3mg/kg which strongly correlated with cyclosporine levels. Since early 2002 we have adopted both these strategies in an attempt to reduce GVHD in myeloblative HSCT but still maintain disease free survival. Consecutive myeloblative allogeneic HSCT patients (n=47, median age 41 yrs, 28 sibling or family, 19 unrelated) underwent HSCT using cyclosporine 1mg/kg, standard dose methotrexate and prednisone commencing at D14 0.5mg/kg, according to Ruutu et al. All sibling allograft patients underwent conditioning with Bu/Cy whereas unrelated recipients received Cy/TBI. This group was compared with 94 historical controls for age and disease status (median age 36 yrs, 63 sibling or family, 31 unrelated). At a median of 1 year follow up (range 100–600 days), overall and disease free survival is significantly increased in the low dose cyclosporine/prednisone arm (OS: 75% vs 50% at 1 yr, p=0.04). Acute GVHD (II–IV) was similar in both arms at D100 with a trend to less GVHD in the low dose cyclosporine/prednisone arm (20% vs 30%, p=0.1). These results suggest that the low dose cyclosporine/prednisone regimen has controlled GVHD whilst maintaining an adequate GVL effect. Randomised trials using this regimen may be warranted to fully determine its place in allogeneic HSCT prophylaxis.

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Radiotherapy Post Autologous Stem Cell Transplantation in Patients with Lymphoma Not Reached Complete Response.

Blood ◽

10.1182/blood.v106.11.5473.5473 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5473-5473

Author(s):

Naibai Chang ◽

Xichun Gu ◽

Ling Zhu ◽

Jianping Wei ◽

Shengming Zhao ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Disease Free Survival ◽

Complete Response ◽

Hematologic Toxicity ◽

Free Survival ◽

Disease Free

Abstract Objective: Anthracycline-based chemotherapy induces 50%–70% of CR in patients with lymphoma, but only 30%–40% of long-term disease-free survival. Salvage chemotherapy with autologous stem cell rescue is required in patients with aggressive disease or never achieve CR with conventional chemotherapy,but the relapsed rate is still high. The purpose of this study was to evaluate radiotherapy post autologous stem cell transplantation in such group of patients. Methods: 15 patients who underwent autologous stem cell transplantation during 1992–1998 were enrolled in this study. Conditioning regimen was CBV (cyclophosphomide + carmustine + etoposide). Radiotherapy was started on day +50(31–90). All patients were followed up until January 2005. Kaplan-Mier survival analysis was made by using SPSS10.0 software. Results: There were 14 patients with non-Hodgkin lymphoma and 1 with Hodgkin disease enrolled. Male:female=11:4. Median age was 40 (30–64). At least 6 cycles of induction chemotherapy were given before transplantation. There were 3 patients in progression disease, 1 in stable disease, and 11 in partial remission before transplantation. Three patients received total lymph node irradiation (TLI). Seven patients received TBI(200cGY)+involved field irradiation therapy(IFIT). Five were treated with IFIT. All patients acheaved complete response(including 1 CRu) after radiotherapy. Three patients relapsed. One patient treated with TBI+IFIT relapsed at 6 months later. Two patients treated with IFIT relapsed at 8 and 36 months later respectively. The mean disease-free survival and overall survival were 10.84(SD1.37,95%CI) years and 11.89(SD1.35,95%CI) years respectively. The estimatrd 10-year disease-free survival and Overall survival were both 73%. One patient developed AML at 86 month. Grade III–IV hematologic toxicity was seen in 2 patients. Conclusions: Post ASCT radiotherapy is safe and tolerated. Relaps rate is low. Patients who received TLI or TBI+IFIT seem to have better outcome than that received IFIT only.

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Early Mixed Chimerism After Allogeneic Stem Cell Transplantation with the Reduced-Toxicity IV Busulfan-Fludarabine (BuFlu) Regimen Does Not Independently Affect Long-Term Prognosis for Patients with AML/MDS.

Blood ◽

10.1182/blood.v116.21.3446.3446 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3446-3446

Author(s):

XiaoWen Tang ◽

Marcos De Lima ◽

Wei Wei ◽

Alexandre Chiattone ◽

Peter F. Thall ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Disease Free Survival ◽

Mixed Chimerism ◽

Free Survival ◽

Conditioning Therapy ◽

Reduced Toxicity ◽

Disease Free

Abstract Abstract 3446 Background: The achievement of a fully chimeric state, as opposed to mixed chimerism, has been associated with a more favorable outcome after allogeneic stem cell transplantation (allo-SCT) for leukemia. When using the reduced-toxicity IV Busulfan-Fludarabine (Bu-Flu) regimen (de Lima et al, BLOOD 2004;104:857-64) we were intrigued by a seemingly high incidence of early (day+30) mixed chimerism, yet a low incidence of serious toxicity, GvHD and high overall and disease-free survival, especially for patients transplanted in (any) remission (CR). We hypothesized that the introduction of highly sensitive PCR-based chimerism assessment technique, as well as separately assaying myeloid- and T-cell chimerism might provide more reliable data for assessing the prognostic value of chimerism in reference to overall (OS) and disease-free survival (DFS) after allo-SCT. Patients and methods: Chimerism assay was performed with PCR-based technique on informative loci, and multi-variate Cox models including chimerism and other covariates were fit for OS and DFS (See Table 1). Results: 206 AML/MDS patients were treated on two consecutive protocols with Flu at 40 mg/m2 daily for 4 days, each dose followed by IV Bu at 130 mg/m2 or pharmacokinetically targeted to an average systemic exposure of 6,000 mcMol-min. Recipients of an unrelated or one-Ag mismatched related graft received rabbit-ATG at a total dose of 4 mg/kg on days -3 to -1. GvHD prophylaxis was Tacrolimus with mini-dose MTX (5 mg/m2) on post-transplant days 1, 3, 6, and 11. There were 98 females and 108 males at a median age of 47 years (range 16–66). Sixty-six patients were in CR1, 48 in CR2, 18 had 1st chemotherapy-refractory relapse, 20 were in 1st or 2nd untreated relapse, 37 had primary induction failure, while 17 had high-risk MDS. One patient died before day 30, without chimerism studies, and 11 recovered with refractory leukemia. Median follow-up of patients still alive is 5.5 yrs (range 1.3–8.6). 193 patients who engrafted and were in CR on day +30 had chimerism analysis performed, 64% were full donor chimeras, and 36% had mixed chimerism (≥1% remaining host cell-derived DNA). As expected, being in CR prior to SCT and, if transplanted with active disease, to engraft and remain in CR or to achieve CR, respectively, were important predictors for survival. A cytogenetic “bad” prognostic subgroup (e.g. -5/-7), was of adverse importance. However, in the multivariate model neither higher age, up to age 65, or attainment of full vs. mixed donor chimerism by day +30 were of additional predictive value for either OS or DFS. (See Table 1). Conclusion: When the reduced-toxicity IV Bu-Flu regimen is used as conditioning therapy for AML/MDS only cytogenetic subgroup (Bad/others) and disease state (CR/No CR) at the start of conditioning therapy influenced DFS and OS. Neither patient age nor attaining complete chimerism on BMT day +30 were independently predictive of an altered prognosis in reference to OS and DFS. Disclosures: No relevant conflicts of interest to declare.

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Faisability and Results of Autologous Stem Cell Transplantation In Lymphoma Patients Over 65 Years Old.

Blood ◽

10.1182/blood.v116.21.4593.4593 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4593-4593

Author(s):

Adrian Tempescul ◽

Jean-Christophe Ianotto ◽

Jean-Richard Eveillard ◽

Gaelle Guillerm ◽

Fontanet Delices Bijou ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Elderly Patients ◽

Disease Free Survival ◽

Free Survival ◽

Younger Patients ◽

Significant Difference ◽

Two Populations ◽

Disease Free

Abstract Abstract 4593 Introduction: The incidence of lymphoma is increasing in the western population. Autologous stem cell transplantation (ASCT) is the standard consolidation procedure in patients with lymphoma expressing bad features at the time of diagnosis or in patients relapsing after a first line of chemotherapy (or radiotherapy). It has already been proven that ASCT improves the overall survival and the disease free survival in younger patients. No data are available for the feasibility and the results of ABSCT in elderly patients (OMS defines elderly as age superior to 65 years). Purpose: We performed a retrospective study in our centre, comparing the feasibility and the results of ABSCT in elderly patients with lymphoma compare to patients younger than 65 years old. Patients and Methods: We identified 147 patients who underwent ASCT transplantation in Brest Transplantation Centre. Ninety-four patients were younger than 65 (mean51.44years) and 53 patients were older (mean 67.86 years). Results: Transplantation related mortality (TRM) (up to 100 days post ASCT) was similar for the two populations. There was no statistically significant difference between the two populations regarding the number of units of RBC and platelets transfused, the number of CD 34 reinjected and infectious complications. There was a statistically significant difference between the two populations regarding the duration of aplasia: 11.21 days in younger patients and 11.89 days in elderly population. There was no statistically significant difference between the two populations regarding the overall survival (OS) and the disease free survival (DFS). Conclusion: Our retrospective, monocentric, comparative study showed that ACST could be performed in selected elderly patients (over 65 years old) with no significant difference regarding TRM, DFS and OS but a little bit longer period of aplasia: 11.21 days for young patients and 11.89 in elderly (p-0.0005). Disclosures: No relevant conflicts of interest to declare.

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Immune Reconstitution Impact on Overall Survival after Hematopoietic Haploidentical Stem Cell Transplantation

Blood ◽

10.1182/blood.v128.22.5779.5779 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5779-5779 ◽

Cited By ~ 1

Author(s):

Ana Perez-Corral ◽

Nieves Dorado ◽

Virginia Pradillo ◽

Jorge Gayoso ◽

Javier Anguita ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Cumulative Incidence ◽

Myeloid Leukemia ◽

Immune Reconstitution ◽

Disease Free Survival ◽

Free Survival ◽

Haploidentical Transplantation ◽

Disease Free

Abstract Introduction: Early immune reconstitution (EIR) is clinically relevant for the outcome of allogeneic hematopoietic stem cell transplantation. In the setting of unmanipulated haploidentical transplantation (Haplo-HSCT), some groups have identified the absolute leukocyte count on day +30 (ALC30) as an independent prognostic factor in terms of overall survival (OS), disease free survival (DFS) and infectious mortality (IM). The aim of this study was to evaluate the impact of EIR on OS, DFS and IM among patients who underwent Haplo-HSCT with postransplant cyclophosphamide (PTCy) at our institution. Patients and methods: Sixty-six patients received a Haplo-HSCT at our institution from July 2011 to February 2016. Conditioning regimen consisted of fludarabine, cyclophosphamide and busulfan. Forty-five percent of the patients received a myeloablative regimen, including busulfan for 3 or 4 days, while 55% were conditioned using a reduced intensity regimen with 1 or 2 days of busulfan. Graft-versus-host disease (GVHD) prophylaxis was based on PTCy, cyclosporine and mycophenolate mofetil. EIR was assessed by means of ALC30 (cellular analyzer DXH, Beckman Coulter®), CD3+ lymphocyte count on day +30 (CD3-30) and NK-lymphocyte count on day +30 (NK30), both determined by multiparametric flow cytometry (FC500 and Navios, Beckman Coulter®). The Kaplan-Meier method was used to evaluate OS rate and DFS rate. Differences in survival rate were assessed using the log-rank test. P values <0.05 were considered statistically significant. Results: We analyzed 66 patients, with a median follow-up of 17 months (8-31). The median age of the patients was 43 years (range 30-57), 77% were men. The diagnosis were: acute myeloid leukemia 33%, acute lymphoid leukemia 8%, chronic myeloid leukemia 6%, Hodgkin lymphoma 21%, non-Hodgkin lymphoma 17%, myelodysplastic syndrome 8%, myelofibrosis (MF) 4%, others 3%. Most patients were in complete remission at the time of the transplant (56%), while 21% were in partial remission and 23% with overt disease. CMV reactivation was documented in 74% of the patients, 8% developed a proven invasive fungal infection and 36% suffered from hemorrhagic cystitis. Median OS and DFS were 17 (8-31) and 13 months (7-26), respectively. IM rate was 27% at the end of follow up. ROC curves were used to determine the optimal cut-off values for each of the studied variables: 300 cells/µL for ALC30, 120 cells/µL for CD3-30 and 40 cells/µL for NK30 were chosen. Those patients with an ALC30 ≥ 300/µL had longer OS (p=0.001) and DFS (p=0.005). Median OS and DFS were 25 months vs. not reached (NR) and 13 months vs. NR respectively. Patients with CD3-30 ≥120/µL had better OS (p=0.07, non-significant) and similar DFS than those with CD3-30 <120/µL. No differences were observed for the NK30 in terms of OS and DFS. Cumulative incidence of IM was significantly lower in patients with an ALC30≥300 (p=0.001). Cumulative incidence of relapse was not affected by ALC30. Patients with CD3-30>120/µL had a lower incidence of relapse than patients with CD3-30<120/µL (p=0.06, non-significant). Conclusions: Our study supports the independent prognostic significance of early immune reconstitution after unmanipulated haploidentical transplantation with postransplant cyclophosphamide, previously described by other groups. Patients with an ALC30 count over 300 cells/µL have a statistically significant better overall survival, disease free survival and a lower cumulative incidence of infectious mortality. However, ALC30 seems to have no correlation with relapse rate. CD3+ and NK-cell total counts on day 30 seem to have less prognostic impact, according to our study. Disclosures No relevant conflicts of interest to declare.

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Clonal Gammopathies Following Reduced Intensity Conditioning Transplantation with Fludarabine, Busulphan and Alemtuzumab for Myeloid Malignancies Predict Improved Overall Survival.

Blood ◽

10.1182/blood.v106.11.1410.1410 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1410-1410

Author(s):

ZiYi Lim ◽

Antonio Pagliuca ◽

Wendy Ingram ◽

Dragana Milojkovic ◽

Mojtaba Akthari ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Disease Free Survival ◽

Autoimmune Disorders ◽

Disease Stage ◽

Reduced Intensity Conditioning ◽

Free Survival ◽

Myeloid Malignancies ◽

Disease Free

Abstract Clonal gammopathies and autoimmune disease following standard conditioning haematopoietic stem cell transplantation (HSCT) are thought to reflect immune dysregulation post HSCT. Serial serum protein electrophoresis was performed on 124 patients with myeloid malignancies undergoing Alemtuzumab based reduced intensity conditioning (RIC) HSCT. The median age of patients was 53 years (range 22–72), with a median follow-up of 521 days (range 82–2096). The median follow-up for survivors was 720 days (range 82–2096). The majority of patients were treated for myeloid malignancies: MDS 84, AML 28, CML 10, others 2. There were 45 sibling and 79 VUD allografts. All patients received the same RIC protocol with FBC (30mg/m2 fludarabine iv day −9 to −5, 4 mg/kg busulphan oral from day −3 to −2; and 20 mg alemtuzumab iv from day −8 to −4) conditioning with cycloporine A for GvHD prophylaxis. Patients with autoimmune disorders or clonal gammopathies prior to transplant were excluded from the study. We observed the presence of clonal gammopathies in 49 patients (40%). On analysis of immunoglobulin sub-classes, the M component was identified as monoclonal in 21 (43%), biclonal in 16 (33%) and oligoclonal in 12 (24%). The predominant Ig isotype was IgG (84%), and gammopathies were present for a median time of 138.5 days (range: 27–462). The kappa:lambda ratio between samples was 1.6:1. The median level of gammopathies was 2.6 g/l (range 1.0–16.5). There was no evidence of plasma cell dyscrasia on bone marrow assessment in any of the patients. We compared the characteristics of patients with and without gammopathies. There were no significant differences in donor or recipient age, sex, disease type, stem cell source, stem cell dose. The incidence of viral infections, acute GvHD, donor lymphocyte infusion (DLI) was similar between the groups. However, patients with gammopathies were more likely to have chronic graft versus host disease (GvHD) (p=0.006). Bone marrow chimerism was available for analysis on 45 patients. At time of detection of gammopathy, 34 patients (76%) had achieved full donor chimerism, and 11 patients (24%) were mixed donor chimerism. Of the entire group of 124 patients, 11 patients (9%) developed autoimmune disorders. There was however no association between the presence of autoimmune disorders and clonal gammopathies (p=0.50). When patients with gammopathies were compared with those without, there was a significant difference in both disease free survival (54% vs 24%, p=0.012), and overall survival (69% vs 45%, p=0.007). On univariate analysis, early disease stage and presence of gammopathy were significant predictive variables for improved disease free survival and overall survival. On multivariate analysis, disease stage was the only independent variable for disease free survival (p<0.01, HR 2.345, 95% CI 1.282–4.288), and both disease stage (p=0.05, HR 1.901, 95% CI 1.000–3.615) and presence of gammopathy (p=0.01, HR 0.421, 95% CI 0.217–0.815) were independent predictors of overall survival. The role of humoral responses following transplantation is still undefined, and it is possible that the gammopathies seen in our cohort are a surrogate response to a heterogenous group of stimuli. Clonal gammopathies are a frequent and benign occurrence following RIC HSCT, and its appearance may define a subgroup of patients with a favourable overall outcome.

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Allogeneic Stem Cell Transplantation from Unrelated Donors within the Seventh Decade of Life.

Blood ◽

10.1182/blood.v106.11.2062.2062 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2062-2062

Author(s):

Joachim Dahlke ◽

Tatjana Zabelina ◽

Francis Ayuk ◽

Jens Panse ◽

Heike Schieder ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Disease Free Survival ◽

High Dose ◽

Free Survival ◽

Disease Free

Abstract We analyzed the outcome of 28 patients who were treated within prospective treatment protocols to investigate the feasibility of unrelated stem cell transplantation for patients with haematological malignancies within the seventh decade of life. Twenty-eight patients with a median age of 62 years (range 60–70) were enrolled. Twenty-six received a dose-reduced conditioning regimen while two patients were transplanted after standard conditioning regimen, and eight of the patients had received at least one prior high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. Diagnoses were leukaemia (AML: n=10; ALL: n=1; CML: n=2), MDS (n=5), myelofibrosis (n=3), multiple myeloma (n=6) or non-Hodgkin’s lymphoma (n=1). No primary graft-failure was observed, and the median number of days to leucocyte and platelet engraftment was 18 days and 23 days, respectively. Acute GvHD grade II–IV was seen in 35% of the patients, chronic GvHD was seen in 56% of the patients. The one-year cumulative incidence of treatment-related mortality was 25%. The four-year estimated overall- and disease-free survival was 49% and 40%, respectively. Unrelated stem cell transplantation in patients within the seventh decade of life is a feasible treatment option and may induce long-term disease-free survival.

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