Morbidity and Mortality Later Than 2 Years After HSCT. A Sinle Institution Experience.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4508-4508
Author(s):  
Hideki Akiyama ◽  
Wataru Munakata ◽  
Takeshi Kobayashi ◽  
Kazuhiko Kakihana ◽  
Takuya Yamashita ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Laboratory Data ◽  
Regular Insulin ◽  
Pulmonary Complications ◽  
Secondary Malignancy ◽  
Hematopoietic Stem ◽  
Renal Complication ◽  
Long Term Follow Up

Abstract Abstract 4508 Long-term follow-up data of the patients who underwent HSCT more than 2 years ago at a single institution in Japan was presented. The patients who received first allogeneic hematopoietic stem cell transplantation (HSCT) at Tokyo Metropolitan Komagome Hospital between January, 1990 and December, 2007 under hematology division were included. Follow-up data were obtained annually from the medical records if the patients visited our institution regularly. If the patients were not followed in our institution, follow-up data were requested to the hospitals where the patients had been followed or questionnaires were sent directly to the patients unless their addresses are not known. These letters were sent annually. The most recent laboratory data and any kind of complications under treatment including hypertension, hyperlipidemia, diabetes including usage of insulin, renal failure, dialysis, and any kind of malignancies were requested to be reported. Survival was the most primitive data and the reason of death was defined by one of the authors, HA. Chronic GVHD was excluded from the independent etiology of death. Progression of the disease or complications of the treatment for the progressive disease were considered to be due to relapse. The incidence of each complication was calculated using the number of the patients whose data are available. In total, 622 patients had received transplantation and 370 patients survived more than 2 years. During last two years, 211 patients had been followed in our institution while 74 patients by the institutions outside. Letters were sent directly to rest of surviving patients. As the result, 6 patients could not be reached by any method. Letters had been received without response in 15 patients. 72 patients died later than 2 years after transplantation. Relapse was the most important reason of death even more than 2 years after the transplantation. Although the incidence declined annually, the latest relapse was observed in the patient with CML almost 15 years after the transplantation. Pulmonary complications including bronchiolitis obliterans and infections followed. Secondary malignancy was the reason of death in 7 patients. Chronic kidney disease was already observed in 27 % of the patients who survived 2 years after transplantation and one of the devastating complications. In total of 7 patients needed to start regular dialysis or kidney transplantation and another 2 patients showed eGFR level of less than 15 ml/min/m2. Nephrotic syndrome was another renal complication observed in 4 patients. Hypertension was reported on 46/244 (19%) of the patients. Diabetes was reported on 27/241 (11.2%) and 13 of them were on regular insulin treatment. Definitive diagnostic criteria of diabetes were not indicated on this analysis suggesting higher incidence of glucose intolerance in these patients. There were 14 patients developed secondary malignancies diagnosed later than 2 years after transplantation and oral mucosa, tongue, esophagus and colon were the main organs involved. Physicians taking care of those patients were recommended to check kidney function and gastrointestinal tract including head/neck, esophagus and colon for secondary malignancy, as well as hematological status. Disclosures: No relevant conflicts of interest to declare.

Long-Term Follow-up of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Severe Alpastic Anemia After Cyclophosphamide Plus Antithymocyte Globulin Conditioning Regimen,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4090-4090
Author(s):  
Johanna Konopacki ◽  
Raphael Porcher ◽  
Marie Robin ◽  
Sabine Bieri ◽  
Jean Michel Cayuela ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Long Term Follow Up

Abstract Abstract 4090 Background: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) from an HLA- identical sibling is the treatment of choice for young patients with acquired severe aplastic anemia (SAA). Due to increased rates of secondary solid cancer in patients with SAA who received an irradiation-based conditioning regimen, we decided 2 decades ago to use the association of Cyclophosphamide (CY) and Antithymocyte globulin (ATG). We report here the long-term follow-up of patients who underwent HSCT from an HLA-identical related donor after this conditioning regimen. Patients and Methods: 61 consecutive patients with SAA who received a first transplantation from June 1991 to February 2010 in our center were included. Patients with Fanconi anemia or other congenital bone marrow failure were excluded. The conditioning regimen consisted in CY (200mg/Kg) and ATG (2.5 mg/kg/day × 5 days). The donors were HLA-identical siblings in 60 cases and family HLA-matched in 1 case. Graft-versus -host disease (GvHD) prophylaxis associated cyclosporine and methotrexate (days 1, 3, 6 and 11). Long-term clinical outcome, immune recovery and quality of life were assessed. Results: The median age was 21 years [range: 4–43], 41 being adults. Median duration of the disease before HSCT was 93 days. Most of the patients had idiopathic aplastic anemia (n=49, 80%). Median time from diagnosis to HSCT was 3 months (range, 1 to 140). All but 2 patients received bone marrow as source of stem cells and all but 2 engrafted (primary graft failure= 3.4%) with a neutrophils count > 0.5 G/L and a platelets count >20 G/L after a median of 23 (range, 19 to 43) and 21 days (range, 10 to 177), respectively. In patients who had achieved neutrophil recovery, no secondary graft failure was observed. Cumulative incidence (CI) of acute grade II-IV GvHD was 23% (95%CI, 13 to 34) and 18 patients developed chronic GvHD (CI: 32%, 95% CI, 20 to 46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic GvHD (p=0.017). With a median follow-up of 73 months (8 to 233), the estimated 6-year overall survival was 87% (95%CI, 78 to 97). At 72 months, the CI of secondary malignancies was 9%, 10 patients developed avascular necrosis (21% CI), 12 patients were diagnosed with endocrine dysfunctions (19% CI) and 5 presented cardiovascular complications (CI of 10%). The CI of bacterial, fungal and viral infections were 25% (95% CI, 15 to 36), 8% (95% CI, 3 to 17) and 61% (95% CI, 46 to 73) at 72 months, respectively. At 2 years post HSCT, the immune reconstitution was normal for CD3, CD8 T-cells, B-cell and NK-cell but still incomplete for CD4 T-cells. A FACT-BMT questionnaire of quality of life (QOL) was sent to all survivors (n= 53) of who 26 accepted to respond to the questionnaire. There was no evidence for a change in QOL perception with time after transplantation. Our data were compared with those obtained from HSCT recipients from a Swiss transplant center (n=125 patients), mainly transplanted for hematological malignancies. The perception of QOL in patients who were transplanted for SAA was similar to the group of patients who were transplanted for other reason than SAA. Conclusions: Our results confirm that HSCT from HLA-identical sibling donors after CY-ATG conditioning regimen is a curative treatment for patients with SAA, with an excellent long-term outcome. We found an increased risk of chronic GvHD associated with the number of infused CD3 cells. Furthermore, we also found non negligible late complications as well as a similar quality of life with patients transplanted for hematological malignancies. Improving long-term health conditions must thus be a priority field for research, exploring the use of new conditioning regimen as well as new GvHD prophylaxis to improve the quality of life post HSCT of such patients. Disclosures: Peffault de Latour: Alexion: Consultancy, Research Funding.

Long-Term Follow-up Results Over 7 Years for Survival, and Safety with Imatinib Mesylate Accompany with Allogeneic Transplantation for Chronic Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4529-4529
Author(s):  
Jun Wang ◽  
Aining Sun ◽  
Wu Depei ◽  
Huiying Qiu ◽  
XiaoWen Tang
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Allogeneic Transplantation ◽  
Cytogenetic Response ◽  
Hematopoietic Stem ◽  
Long Term Follow Up

Abstract Abstract 4529 Objective: To observe the efficacy and safety of imatinib mesylate (IM) accompany with allogeneic transplantation for chronic myeloid leukemia (CML). Methods: During the period from January 2003 to August 2011,we retrospectively observed 95 patients with CML receiving IM for a minimum of 4 months before allogeneic hematopoietic stem cell transplantation (HSCT). Patients with advanced CML received IM from 3 month after transplantation for 12 months. Results: Among 95 enrolled patients (CML-CP 76, CML-AP 10, CML-BP 9), types of transplantation: sib-matched HSCT 64, unrelated-HSCT 19, haplo-HSCT 12. For the whole patients, 7 year overall survival (OS) is 80.5%, and disease free survival (DFS) is 74.5%. Complete hematologic response (CHR) is 93.6%, complete cytogenetic response (CCR) is 84.5%, major cytogenetic response (MCR) is 60.3% at 7 year. For CML-CP1, OS is 83.2% and CML-AP/BC is 33.3% (P<0.05). Compared patients of advanced CML achieving CP2 after IM and with no CP2,the former has better results of CCR or MCR, OS and PFS (P<0.05). The total treatment related mortality (TRM) is 16.8%. Cox multivariate regression analysis of prognostic factors indicates that status of CML and severe acute graft-versus-host disease (aGVHD III-‡W) retain independent predictive value. No increase in rates of serious adverse events was observed with continuous use of IM for up to 7 years. Conclusions: For chronic myeloid leukemia, combining with imatinib mesylate and allogeneic transplantation is a good strategy, with favorable long-term follow-up results and acceptable TRM, especially for the patients with advanced CML. Disclosures: No relevant conflicts of interest to declare.

Long-Term Follow-up of a Randomized Trial Comparing Cyclosporine and Short Course Methotrexate with Cyclosporine and Mycophenolate Mofetil for Graft Versus Host Disease Prophylaxis in Myeloablative HLA-Identical Sibling Hematopoietic Cell Transplantation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3073-3073
Author(s):  
Betty K. Hamilton ◽  
Brian J. Bolwell ◽  
Matt Kalaycio ◽  
Lisa Rybicki ◽  
Rabi Hanna ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Short Course ◽  
Gvhd Prophylaxis ◽  
Significant Difference ◽  
Long Term Follow Up

Abstract Abstract 3073 The combination of a calcineurin inhibitor and methotrexate (MTX) is currently the gold standard for GVHD prophylaxis. MTX, however, is associated with toxicity including mucositis, delayed engraftment and other organ toxicity. We conducted a randomized trial comparing cyclosporine (CSA) and mycophenolate (MMF) with CSA and MTX for GVHD prophylaxis in recipients of myeloablative allogeneic hematopoietic cell transplants (HCT) with matched sibling donors (Bolwell et al, BMT 2004, 34:621). We showed reduced toxicity without an increased relapse rate in patients treated with MMF instead of MTX. Now, with a median follow up of almost 10 years, we report long-term outcomes of this study. From May 2001 until February 2003, 40 patients with hematologic malignancies were randomized to receive CSA (300mg/m2) and MMF (500mg three times daily) or CSA and short course MTX (5mg/m2 days 1, 3, 6, 11). Study endpoints included incidence of acute GVHD, severity of mucositis, time to engraftment of neutrophils and platelets and 100 day survival. Baseline variables were compared using the Wilcoxon rank sum tests or Chi square test. Outcomes were compared between MMF and MTX using the Pepe-Mori test. The two treatment arms were similar in patient characteristics such as age, disease, disease status, and CMV status. In total, 21 patients received MMF and 19 patients received MTX. The study was stopped early when an interim analysis demonstrated less mucositis, shorter length of stay and no difference in the incidence of GVHD or relapse with a median of 6 months of follow up. Currently, with a median follow up of 119 months (range 46–129 months) in survivors, there remains no difference in the incidence of or degree of acute (p≥0.35) or chronic GVHD (p≥0.53), overall survival (p=0.84) or relapse (p=0.41). There are 6 long term survivors in the MMF arm and 4 in the MTX arm. Of those that received MMF, 3 have mild chronic GVHD of the skin or upper GI tract and 1 has moderate chronic GVHD involving the skin, fascia, and vulva. Three of those who received MTX have mild chronic GVHD primarily of the skin. Only 3 patients (2 MMF and 1 MTX) remain off of all immunosuppression without evidence of GVHD. Eight patients (38%) died of relapse in the MMF arm versus 7 (37%) in the MTX arm which was also not statistically different (p=0.86). Death from GVHD was similar in both groups. Results from this updated analysis support our original conclusion that the combination of CSA and MMF results in decreased mucositis and more rapid engraftment compared with CSA and MTX, with no significant difference in GVHD, survival or relapse on long-term follow up. The primary limitation of this trial remains sample size and the ability to detect modest differences in survival. There remains limited data and virtually no long-term data comparing standard MTX based regimens with less toxic prophylaxis in myeloablative allogeneic HCT. Larger prospective studies with long-term follow up comparing GVHD prophylaxis regimens are warranted. Disclosures: No relevant conflicts of interest to declare.

Long Term Follow-up of Hematopoietic Stem Cell Transplantation (HSCT) for Primary Plasma Cell Leukemia (pPCL): Final Results of a Prospective Study of IFM Group

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4612-4612 ◽  
Author(s):  
Bruno Royer ◽  
Momar Diouf ◽  
Murielle Roussel ◽  
Lionel Karlin ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Prospective Study ◽  
Proteasome Inhibitor ◽  
Chronic Gvhd ◽  
Prospective Trial ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Long Term Follow Up ◽  
A Prospective Study

Abstract Introduction: pPCLis a rare form of multiple myeloma (MM) with very poor outcome. Current strategies including novel agents and transplantation (auto or allo-HSCT) may improve survival but the prognosis remains poor. The IFM recently published results from a prospective study incorporating tandem auto/allo-HSCT or auto/auto and maintenance after alternate induction (doxorubicin-bortezomib-cyclophosphamide and dexamethasone: PAD/VCD) in 40 pPCL patients. We report here outcomes of patients who effectively underwent second transplant (auto or allo) with long-term follow-up. Methods: 24 over 40 patients actually received second transplant:allo-HSCT (as per protocol) forpatients< 60 years-old with a donor, second auto-HSCT for others. At time of second transplant, response rates were: sCR (n=1), CR (n=8), VGPR (n=10), PR (n=5) (cf table). 7 patients received high-dose melphalan (HDM)/auto-HSCT followed by maintenance consisting in Bortezomib-Lenalidomide-Dex (VRD) every 3 months and Lenalidomideduring other months for 1 year. 17 others patients underwent allo-HSCT: syngenic(n=1) or reduced intensity conditioning (RIC)-Allo (n=16). The conditioning regimens for allo were: fludarabin-busulfan-antithymoglobulin(n=13), fludarabin-melphalan(n=1), bortezomib-fludarabin-melphalan(n=2) and HDM for syngenic(n=1). They were grafted with peripheral blood stem cells except 1 who received bone marrow and 1 cord blood unit, from related (n=9) or HLA-matched unrelated donors (n=8): median infused CD34 cells was 6.8 106/kg [3-8.5]; all pts receivedciclosporine+/-methotrexate as GvHD prophylaxis. Results: As of June 2016, median follow-up from diagnosis was44.7months[41.0;57.6], 10 patientswerestillalive.MedianPFS for allo and auto ptswas18.5months[17.8;-] and 50.1months[25.6;-]respectively ;medianOSwas39.3months[26.6;-] and notreached,respectively.Inlandmarkanalysisfromdate of second transplant, PFSwas12.2 months [8.1 ;-] for allo pts and 40.0months[17.7;-] for auto pts (p=0.085); OSwas30.0months[28.6;-] and notreached,respectively(p=0.026). 2 allo ptsdiedbefored100evaluation ; 18 patients (75%)werein VGPR orbetter : sCR=2, RC=8, VGPR=8 ; 4 patients (17%)werein PR. For allo-HSCT : 6patients developed acute GvHD which responded to steroid in 5 cases and 1 was steroid-resistant and responded secondary to anti-IL2Rα antibody;5 patients experienced chronic GVHD (mild [n=4], extensive [n=1]).3 patients received 3 months after allo as immunomodulation, donor lymphocyte infusions plusLenalidomide-Cyclophosphamide-Fludarabin(n=1), Bortezomib (n=1) and Lenalidomide (n=1): one patient in PR achieved CR and the two others in VGPR maintained their response.Day 100 treatment-related mortality was 12%: 2 patients had Epstein-Barr virus reactivation, with 1 experiencing neuromeningeal relapse of pPCL and 1 concomitant disseminated toxoplasmosis. For auto-HSCT: as per protocol, 6 received a second HDM/auto, and 1 declined. Consolidation with VRD/Len was initiated in these 7 patients: 4 receiving the planned 1 year of treatment and 3 discontinuing after 4, 8, and 10 months as a result of prolonged cytopenia. Conclusion: This is the first large prospective trial for pPCL patients including tandem auto/auto-HSCT or tandem auto/RIC-allo after induction including proteasome inhibitor. This approach is feasible, and induces high response rate but relapses remain frequent especially after RIC-allo. Tandem auto/auto plus maintenance may be superior to tandem auto/alloregarding PFS and OS. In a future trial, we will investigate tandem auto/auto after induction incorporating novel proteasome inhibitor, anti-CD38 monoclonal antibody and Lenalidomide, and followed by consolidation and prolonged maintenance. Table: characteristics of Patients Table: characteristics of Patients Figure PFS / OS Figure. PFS / OS Disclosures Roussel: amgen: Consultancy; Janssen: Consultancy; celgene: Consultancy. Karlin:janssen-cilag: Consultancy, Honoraria; amgen: Consultancy, Honoraria; celgene: Consultancy, Honoraria; Bristol: Consultancy; takeda: Consultancy. Hulin:Janssen: Honoraria; Bristol: Honoraria; Amgen: Honoraria; takeda: Honoraria; celgene: Honoraria. Macro:sanofi: Consultancy; Novartis: Honoraria; Bristol: Consultancy; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgen: Consultancy, Honoraria. Belhadj:janssen: Consultancy; novartis: Consultancy. Chaleteix:Amgen: Honoraria; Janssen: Honoraria. Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Garderet:Takeda: Consultancy; Amgen: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy. Choquet:Janssen: Consultancy; Celgene: Consultancy. Fornecker:Roche: Consultancy; Takeda: Consultancy; Gilead: Consultancy; Mundipharma: Speakers Bureau. Facon:Novartis: Consultancy; Amgen: Consultancy, Speakers Bureau; Millenium/Takeda: Consultancy; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Bristol: Consultancy; Karyopharm: Consultancy. Moreau:Bristol-Myers Squibb: Honoraria; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Celgene: Honoraria.

scholarly journals Encouraging Outcome of Using Sibling HLA-Matched Fresh Cord Blood for Children β-Thalassemia Major Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3459-3459 ◽  
Author(s):  
Jianyun Wen ◽  
Libai Chen ◽  
Sixi Liu ◽  
Yuelin He ◽  
Yongsheng Ruan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Thalassemia Major ◽  
Effective Treatment Option ◽  
Hematopoietic Stem ◽  
Advantages And Disadvantages

Abstract Background: Hematopoietic stem cell transplantation(HSCT) is currently the only curative treatment for thalassemia major (TM). Cord blood (CB) from a sibling has different characteristics from marrow and has potential advantages and disadvantages as a stem cell source. Methods: We conducted a retrospective study of fresh cord blood transplantation (F-CBT) from the matched human leukocyte antigen (HLA)-identical sibling donors in 35 children (median age at transplantation: 4 years, range:1-7 years) with β-TM from June 2010 to December 2016. The conditioning protocol included intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa. Results:The median collected CB volume was 130ml (range: 79-209ml). The median infused total nucleated cell (TNC) dose was 9.38×107/kg (range: 2.73-18.91×107/kg). One patient had graft failure (GF) on +30day after F-CBT and one patient died from respiratory and heart failure that developed from a pulmonary infection. Of the 33 patients who had a successful engraftment, two patients developed grade II~III acute graft-versus-host disease(GVHD); and one with grade I extensive chronic GVHD was observed during the long-term follow-up period. The median time to neutrophil recovery was +27 days (range: +14 to +49days). The platelet and hemoglobin engraftment times were +33 days (range: +19 to +73 days) and +26 days (range: +11 to +74 days), respectively. All the patients were followed up by December 31, 2017; the median follow-up time was 45 months, and the estimated 5-year overall survival (OS) and TM-free survival (TFS) of F-CBT were 97.1% and 94.2%, respectively. Conclusions: F-CBT from a matched HLA-identical sibling donor is an effective treatment option for β-TM in children with less GVHD. Disclosures No relevant conflicts of interest to declare.

Phase II Study of Chemotherapy (Cx) and Stem Cell Transplantation (SCT) for Adult Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LBL): Long-Term Follow-up Results of Japan Clinical Oncology Group (JCOG) Study 9402.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3087-3087
Author(s):  
Teruhisa Azuma ◽  
Kensei Tobinai ◽  
Kunihiko Takeyama ◽  
Taro Shibata ◽  
Haruhiko Fukuda ◽  
...  
Keyword(s):  
Phase Ii ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Pulmonary Complications ◽  
Intrathecal Methotrexate ◽  
Cell Phenotype ◽  
Phase Ii Trials ◽  
Long Term Follow Up

Abstract Abstract 3087 Poster Board III-24 Objective To evaluate the efficacy and safety profile of an intensive induction and post-remission Cx for untreated patients (pts) with adult ALL and LBL, focusing on the long-term follow-up results. Feasibility and efficacy of autologous or allogeneic SCT were also assessed. Patients and Methods We enrolled pts with untreated adult ALL or LBL aged 15 to 69 years. The Cx regimen consisted of induction Cx (vincristine [VCR], cyclophosphamide [CPA], prednisone [PSL], doxorubicin [DXR], L-asparaginase plus intrathecal methotrexate [IT-MTX]) followed by two consolidation Cx regimens (Consolidation A, consisting of daunorubicin, cytosine arabinoside [Ara-C], vindesine [VDS], PSL plus IT-MTX; Consolidation B, consisting of CPA, Ara-C, 6-mercaptopurine [6-MP], VCR plus IT-MTX) with the prophylactic use of granulocyte colony-stimulating factor. Thereafter, interim maintenance Cx including 6-MP and MTX concurrent with CNS prophylaxis (IT-MTX), intensification Cx (VCR, DXR, PSL, CPA, Ara-C and 6-MP) and maintenance Cx (VDS, CPM, PSL, DXR, MTX and 6-MP) were sequentially performed for two years. For pts with 50 years or younger who achieved complete remission (CR) after induction Cx, allogeneic SCT for ALL from HLA-matched related donor and autologous SCT for LBL were to be considered. Primary endpoint was 5-year progression-free survival (PFS). Secondary endpoints included CR rate (%CR), overall survival (OS) and adverse events. Results Among 115 pts who were enrolled between 1994 and 1999, 108 eligible pts (median age, 33.5 years [15-69]) including 96 ALL and 12 LBL pts who received induction Cx were assessed. Seven pts were judged ineligible, including four histologically ineligible pts revealed by institutional or central review. Other major characteristics of the 108 eligible pts were as follows: 54 males (50%); T-cell phenotype, 23 pts (21%); Ph, 24 pts (22%); t(4;11), 2 pts (2%); B-symptom+, 38 pts (35%); PS 2/3, 24 pts (22%). Eighty-seven pts achieved CR (%CR 81%; 95% CI, 72-88%), while five patients (5%) died during induction Cx mainly due to infections. The median OS and the median PFS of the 108 eligible pts were 1.8 years (95% CI, 1.5-2.6 years) and 1.2 years (95% CI, 0.8-1.6 years), respectively. Their 5-year OS and 5-year PFS were 29% and 28%, respectively, with the median follow-up of the censored cases of 9.3 years (range, 2.0-12.3 years). The 5-year OS from the date of SCT of 31 pts who underwent allogeneic (n=19) or autologous (n=12) SCT during 1st CR was 51% (95% CI, 32-67%). Major non-hematologic toxicities of grade 3 or greater included infections (n=24, 21%), pulmonary complications (n=7, 6%) and diarrhea (n=7, 6%). As compared with the investigators' previous phase II trials for ALL and LBL, JCOG9402 improved PFS and OS as compared with JCOG8702 (MST, 1.2 years; 7-year OS, 15%; 7-year PFS, 13%) (Jpn J Clin Oncol 1999;29:340), but did not show improvement as compared with JCOG9004 (MST, 2.2 years; 5-year OS, 32%; 5-year PFS, 26%) (Cancer Sci 2007;98:1350). Conclusion Although the intensified induction and post-remission Cx was feasible and 28% of pts achieved long-term PFS, JCOG9402 failed to show improvement in long-term follow-up results as compared with the investigators' latest historical control. To further improve the therapeutic outcomes of adult pts with ALL and LBL, novel strategies are warranted. Disclosures No relevant conflicts of interest to declare.

HLA-Haploidentical TCR αβ/CD19-Depleted Hematopoietic Stem Cell Transplantation in Children with Fanconi Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2287-2287
Author(s):  
Luisa Strocchio ◽  
Pietro Merli ◽  
Alice Bertaina ◽  
Luciana Vinti ◽  
Letizia Pomponia Brescia ◽  
...  
Keyword(s):  
B Cells ◽  
Fanconi Anemia ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Introduction. Allogeneic HSCT currently represents the only consolidated curative approach for Fanconi anemia (FA) patients, with best results observed in the HLA-identical sibling setting. For patients lacking an HLA-matched related or unrelated donor, haploidentical HSCT virtually assures the opportunity for nearly all patients to benefit from HSCT, offering the advantage of immediate accessibility to the transplant procedure. In order to overcome the limitation of delayed immune recovery, historically associated with this type of allograft, in the last few years we developed a novel method of ex vivo graft manipulation, consisting of the negative depletion of T-cell receptor (TCR) αβ+ T-lymphocytes and CD19 B-cells from peripheral blood stem cells (PBSC) grafts (ClinicalTrial.gov identifier: NCT01810120) (Bertaina el al., Blood 2014). Here we report our analysis in a subgroup of FA patients given TCRαβ/CD19-depleted haploidentical HSCT at our Institution. Patients and methods. Ten consecutive FA patients (6 girls and 4 boys) underwent a TCRαβ/CD19-depleted HSCT from an HLA-haploidentical relative between September 2011 and July 2015. Median age at diagnosis was 6.6 (range 2.7-22.0) years and median age at time of transplantation was 8.1 (range 4.4-22.2) years. The conditioning regimen included Cyclophosphamide 300 mg/m2/day and Fludarabine 30 mg/m2/day for 4 consecutive days (days -6 to -3), with 200 cGy single-dose TBI. Pretransplantation Fresenius® ATG was administered at a dose of 4 mg/kg/day for 3 consecutive days (days -5 to -3) in order to prevent both graft failure and graft-versus-host disease (GVHD). All patients received Rituximab 200 mg/m2 to reduce the risk of Epstein-Barr virus-related post-transplant lymphoproliferative disorders. Selective removal of TCRαβ+ and B-cells was performed on G-CSF-mobilized donor PBSC through labeling with biotinylated anti-TCRαβ antibodies and anti-CD19 antibodies, followed by incubation with anti-biotin antibodies conjugated to paramagnetic beads (CliniMACS; Miltenyi Biotec, Bergisch Gladbach, Germany). No immunosuppressive therapy was administered as post-transplantation prophylaxis against GVHD. Results. The TCRαβ/CD19-depletedgrafts contained a median of 20.40 x106/kg (range 15.80-33.40) CD34+ cells, 5.60 x106/kg (range 1.78-69.60) CD3+ lymphocytes, 0.021 x106/kg (range 0.002-0.043) TCRαβ+ lymphocytes, 5.60 x106/kg (range 1.78-69.60) TCRγδ+ lymphocytes, 0.036 x106/kg (range 0.013-0.079) CD20+ lymphocytes, and 45.30 x106/kg (range 16.2-177.0) NK cells. Engraftment with sustained full donor chimerism was achieved in 9 out of 10 patients, the cumulative incidence of graft rejection being 10% (95% CI, 0-26.8). The patient who rejected his first allograft achieved a complete engraftment after a second HSCT from one-antigen mismatched unrelated donor. No secondary graft failures were observed. The median time for neutrophil and platelet engraftment was 12 days (range, 9-15) and 9 days (range, 8-12), respectively. No patient experienced acute or chronic GVHD in the follow-up period. No transplant-related deaths occurred in our cohort. With a median follow-up of 28 months (range 13.2-39.1), the Kaplan-Meier estimates of OS and DFS were both 100%, while the EFS probability was 90% (95% CI, 47.3-98.5). Discussion. These data suggest that haploidentical HSCT after removal of TCRαβ+ and CD19+ lymphocytes is able to guarantee engraftment with excellent OS and DFS in patients affected by FA. Moreover, given the very low incidence of both acute and chronic GVHD, which has been shown to contribute to the increased risk of developing late post-transplantation malignancies in FA patients, this approach can be considered a very attractive option for FA patients in need of an allograft and lacking an HLA-identical family donor. Disclosures No relevant conflicts of interest to declare.

Long-term follow-up of adult hematopoietic stem cell transplant recipients diagnosed with COVID-19.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19028-e19028
Author(s):  
Stephanie Hoffman ◽  
Pavan Reddy ◽  
John Martin Magenau ◽  
Attaphol Pawarode ◽  
Brian Parkin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Acute Gvhd ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Long Term Follow Up

e19028 Background: Long-term complications of COVID-19 in hematopoietic stem cell transplant (HCT) recipients are unknown. Recent studies have described short term outcomes of COVID-19 infection post allogeneic (allo) and autologous (auto) HCT. In this study we provide long term follow-up of the outcomes of COVID-19 infection in allo and auto HCT recipients. Methods: We performed a retrospective study of adult patients who have received allo or auto HCT and were subsequently diagnosed with COVID-19 infection between March-December 2020. We summarized patient characteristics, laboratory and treatment data related to COVID-19 infection in these patients. Results: In this study, we provide long-term follow-up of over 7 months. Fifteen patients were identified for inclusion (allo n = 12, auto n = 3). Median follow-up was 7.8 months (range 1.9-10.7) for surviving patients. Median age at COVID-19 diagnosis was 55 years (range 24-77). Most patients were > 1 year out from transplant (allo n = 10, auto n = 1, 73%). Two patients (allo n = 1, auto n = 1, 13%) had undergone transplant within the preceding month. Most allo patients (n = 11, 73%) had received myeloablative conditioning. At the time of COVID-19 diagnosis, 9 allo patients (75%) were on immunosuppression (IS) (n = 7 for chronic graft-versus-host-disease (GVHD); n = 2 for GVHD prophylaxis). Eleven patients (73%) required hospitalization (allo n = 9, auto n = 2). Per the National Institutes of Health definitions of COVID-19 illness severity, 3 patients had critical disease (allo n = 2, auto n = 1, 20%), 5 severe (allo n = 5, 33%), 3 moderate (allo n = 2, auto n = 1, 20%), and 4 mild (allo n = 3, auto n = 1, 27%). All patients with chronic GVHD required hospitalization. Two patients died (allo n = 1, auto n = 1, 13%)—both had critical COVID-19 infections, were > 65 years old, > 3 years out from transplant, and had significant comorbidities. The allo patient was receiving prednisone < 1 mg/kg for chronic lung GVHD at COVID-19 diagnosis. Two allo patients developed either acute GVHD or chronic GVHD exacerbation within 3 months of their infection. One patient developed biopsy-proven acute GVHD (max grade III) 3 weeks after her infection and another patient developed a severe exacerbation of chronic GVHD within 3 months—both continue to require multi-modal IS. The remaining 7 patients with chronic GVHD have been maintained on either stable or tapered IS. Conclusions: Given the effect of COVID-19 infection, its impact on HCT recipients is important to define. The majority of HCT patients who contracted moderate-critical COVID-19 infections in our study were either on IS or had significant comorbidities. Our observational data points to the importance of long-term follow-up in HCT patients. Future studies are needed to delineate whether there is a relationship between COVID-19 infection and GVHD development or exacerbation. The role of vaccination in HCT recipients remains to be explored.

scholarly journals Successful Result of 113 Patients for Refractory/Recurrent Leukemia By Allogeneic Hematopoietic Cell Transplantation and Prophylactic Immunotherapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5856-5856
Author(s):  
Jingbo Wang ◽  
Xiaojun Huang ◽  
Ying Hu ◽  
Song Xue ◽  
Haoyu Cheng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Transplantation ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Prolymphocytic Leukemia ◽  
Significant Difference

Abstract Objective: To retrospectively evaluate the results of allogeneic hematopoietic stem cell transplantation for Refractory/Recurrent leukemia. Methods: From July 2012 to May 2016, total 113 patients with Refractory/Recurrent leukemia were enrolled, including 31 cases of ALL, 73 cases of AML and 8 cases of CML-BP, 1 case of Prolymphocytic leukemia. The average leukemia burden was 51% (10-99) in bone marrow before conditioning. Myeloablative conditioning regimens consisted of 13 cases of BuCy, 47 cases of TBI/FLAG, 28 cases of TBI/Cy, and 16 cases of FLAG that followed by reduced-intensified BUCY, 9 cases of CLAG/BuCy. Transplant types included sibling HLA-identical allo-HSCT (n=22) and relative HLA-haploidentical HSCT (n=91). All patients received cyclosporine A, MMF and methotrexate for GVHD prophylaxis. Analyzed outcomes were hematological engraftment, incidence of acute and chronic GVHD, incidence of CMV/EBV infecton, incidence of relapse, and nonrelapse mortality (NRM), Overall survival (OS) and Disease-free survival (DFS). Results: The median mononuclear cells and CD34+ for transfusion were 8.83 (7.02-11.64) ×108/Kg and 2.91 (0.8-8.32) ×106/Kg. 111 patients achieved stable engraftment, 2 patients died of infection before engraftment. The median time of ANC≥0.5×109/L was 16 days(8-29) and the median time of platelet ≥20×109/L was 22 days (8-150). On day 28postallogeneic transplant, 110 patients were in complete remission of bone marrow, 1 patient was in hematologic relapse. Immunity residue were negative in 107 patients and positive in 4 patients. 62 patients developed acute GVHD, the accumulative incidence of aGVHD was (57.6±4.8)%, the accumulative incidence of II-IV grade aGVHD was (47.2±4.8)%, and the accumulative incidence of III-IV grade aGVHD was (25.2±4.1)%. 62 patients developed cGVHD (43 patients extensive, 19 patients limited), the accumulative incidence of cGVHD was (70.2±6.6)% and for extensive type, the accumulative incidence was (43.6±5.2)%. The accumulative incidence of CMV infection was (42.3±4.7)%, and the accumulative incidence of EBV infection was (4.5±2)%. 10 patients developed virus cystitis, and the accumulative incidence was (9.1±2.1)%. The median follow-up time post transplantation was 10 months (1-46), 35 patients occurred hematologic relapsed and the accumulative incidence of relapse was (39.7±5.9)%. For AML, ALL and CML-BP patients, the accumulative incidence of relapse were (33.8±6.9)%, (56.6±11.7)% and (25±15.3)%respectively (p>0.05). On median follow up (10 months), 49 patients died and 64 patients survived. The cause of death included relapse (28 cases), infection (6 cases), GVHD (11 cases) diffuse alveolar hemorrhage (2cases), radiation enteritis (1 case), and TMA (1 case).Among 64 survirors, two-year accumulative incidences of OS were (49.3±5.7)%, and two-year accumulative incidences of LFS were (45.1±5.4). The two-year accumulative incidences of OS for AML, ALL and CML-BP patients were ( 52.4±7.1)%, (28.1±9.7)%,and (87.5±11.7)%respectively (p>0.05). The two-year accumulative incidence of LFS for AML, ALL and CML-BP patients were (49.8±6.5)%, (24.7±9.1)%, and (70±18.2)%respectively (p>0.05). Incidence of relapse, OS and LFS were similar in different conditioning cohorts (p>0.05). There was no significant difference in the incidence of relapse, OS and LFS over two years among patients with C-Kit, FLT3, MLL and without such genes(p>0.05). There is significant difference in incidence of relapse, OS and LFS among patients with different leukemia burdens(p<0.01). Patients with leukemia burden at 10-19% has lower relapse rate but higher OS and LFS compared to patients with leukemia burden at 80%. Incidence of relapse, OS and LFS for the prophylactic immunotherapy cohort were 32.9%, 61.1% and 57.6% respectively, compared to 45.2%, 35.8% and 35% for non prophylactic immunotherapy cohort (p<0.01). Incidence of relapse , OS and LFS for the cGVHD cohort were 12.9%, 68.4% and 66.2% respectively, compared to 78.7%, 13.9% and 12.8% for non cGVHD(p<0.01). Incidence of relapse , OS and LFS for extensive cGVHD cohort were 12.3%, 62.1% and 61.8% respectively, compared to 58.8%, 31.4% and 31.2% for non extensive cGVHD(p<0.01) Conclusion: Our clinical results have shown that the salvaged HSCT is a promising modality for treatment of Refractory/Recurrent leukemia. Especially for Refractory/Recurrent AML and CML-BP. Disclosures No relevant conflicts of interest to declare.

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