Hemophagocytic Syndrome (HPS) Post Reduced Intensity Cord Blood Transplantation (RI-CBT) in Adult Patients with Hematological Diseases.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2743-2743
Author(s):  
Kazuhiro Masuoka ◽  
Shigesaburo Miyakoshi ◽  
Shinsuke Takagi ◽  
Daisuke Kato ◽  
Eiji Kusumi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Risk Factor ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Bone Marrow Examination ◽  
Important Risk Factor ◽  
Adult Patients ◽  
Hematological Diseases ◽  
Gvhd Prophylaxis

Abstract <Introduction> HPS are rare but often-fatal conditions characterized by an inappropriate and sustained activation of the cellular immune system leading to accumulation of activated macrophages and a cytokine storm. HPS consists of primary and secondary Hemophagocytic Lymphohistiocytosis (HLH). Secondary HLH occurs at any age and the genetic contribution remains uncertain. Clinical features in patients with HLH are fever, cytopenias, liver dysfunction, hepato-splenomegaly, and the presence of hemophagocytosis in the bone marrow as well as other reticuloendothelical tissues. We will report on the hematological abnormalities and the clinical course of 20/152 patients who received RI-CBT and developed secondary HLH in adult patients with hematological disease in early phase after RI-CBT. <Object> The 1st purpose was to investigate the incidence of HLH and pattern of chimerism. The 2nd was to identify the risk factors after UCBT. <Patients and Methods> We reviewed medical records of 152 patients with hematological diseases who had received RI-CBT between January 2002 and April 2005 at Toranomon Hospital, Tokyo, Japan. Diagnosis of HLH was made with the followings; high fever, cytopenias, and hemophagocytic findings in bone marrow examination. Time to event curves were plotted by using the actuarial method of Kaplan-Meier, and differences between curves were analyzed by log-rank tests. The following factors were considered potential predictors of outcomes about 2nd purpose: patient’s age, HLA disparity, infused TNC dose/CD34 dose, disease/disease status at transplantation, GVHD prophylaxis and sepsis which coincided with HLH. All factors were tested for the proportional hazards assumption. <Results> Patient’s median age was 55 years (17–79), Primary diseases consisted of standard (n=31) and advanced (n=121). HLA disparities were 4/6 match (n=123), 5/6 (n=22), and others (n=7). Total nucleated cell/CD34 cell dose were 3.46×10E7/kg (1.6–5.2) and 0.78×10E5/kg (0.1–3.3), respectively. Main conditioning regimen was Fludarabine (125mg/m2) +Melphalan (80mg/m2) or Busulfan (8mg/kg) +TBI 4Gy with cyclospoline (n=89) and tacrolimus (n=63) as GVHD prophylaxis and received single cord blood unit. Twenty patients were diagnosis with HLH and the incidence of HLH was 13% (95%CI; 8–18) and median onset day was 18.5 days (range; 10–29). In patients with sepsis (n=46) and without sepsis (n=106), the incidence of HLH was 28% (95%CI; 15–41) and 7% (95%CI; 3–12), respectively (P<0.0002). All patients who were diagnosis with HLH using bone marrow examination achieved 100% of donor chimerism. In multivariate analysis, the most important risk factor of HLH after RI-CBT was sepsis which coincided with HLH at the same times (p<0.05), while other factors did not influence. <Discussion/Conclusion> HLH is fatal complication after allogeneic peripheral stem cell and unrelated bone marrow transplantation. However in RI-CBT, the incidence would be higher and earlier onset than other sources. The most of HLH patients died by multi-organ failure. In this report the most important risk factor was sepsis which coincided with HLH. Figure Figure

Unrelated Cord Blood Transplantation: Comparison After Single Unit Cord Blood Intrabone Injection and Double Unit Cord Blood Transplantation In Patients with Hematological Malignant Disorders. A Eurocord-EBMT Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 223-223 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Marina Podestà ◽  
Dolores Caballero ◽  
...  
Keyword(s):  
Cord Blood ◽  
Median Time ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Myeloablative Conditioning ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
The Impact

Abstract Abstract 223 The use of single cord blood unit for transplantation in adult patients is limited due to the high risk of graft failure and delayed neutrophil and platelet recoveries. The limited hematopoietic progenitors in UCB grafts and their homing after IV injection, have prompted investigators to study the design of delivering CB grafts directly into the bone marrow (BM) space (IBCBT) or to use double cord blood transplantation (dUCBT) to improve engraftment. To evaluate the impact of IBCBT, we made a retrospective based registry comparison with dUCBT performed in the same time period (2006-2010) and reported to Eurocord-EBMT. We included 87 and 149 patients who received either IBCBT or dUCBT, respectively, after a myeloablative conditioning regimen for malignant disorders. IBCBT was performed in 8 EBMT centers whereas dUCBT was performed in 56 EBMT centers. Majority of patients in both groups had acute leukemia. IBCBT patients were older (p<0.001), more frequently received an autologous graft (p<0.001) and had positive CMV serology (p<0.001), and importantly had more advanced disease at transplantation (p=0.04). Median number of infused (after thawing) nucleated cells injected intrabone was 2.5×107/kg and it was 3.9×107/kg in dUCBT (p<0.001). In 72% of both groups, CB grafts were HLA 4/6 (the highest HLA disparity was taken into consideration in dUCBT). Other differences were regarding GVHD prophylaxis that was based on CSA+MMF in 100% of IBCBT and in 62% of dUCBT cases; ATG was used in all IBCBT and 40% of dUCBT. Median follow-up time was 18 months in IBCBT and 17 months in dUCBT. At day 30, cumulative incidence (CI) of neutrophil recovery (ANC >500) was 83% after IBCBT and 63% after dUCBT, and at day 60, it was 90% in both groups; the median time to reach ANC>500 was 23 and 28 days after IBCBT and after dUCBT (p=0.001) respectively. At Day-180 CI of platelets recovery was 81% after IBCBT and 65% after dUCBT (p<0.001) with a median time of 36 days and 49 respectively (p=0.002). At day 100, CI of acute GVHD (II-IV) was 19% and 47% (p<0.001) and chronic GVHD 34% and 37% respectively (p=NS) respectively. Unadjusted 2 years-CI of NRM and RI were 31% and 23% after IBCBT and 35% and 28% after dUCBT, respectively (p=NS). Unadjusted 2 y-DFS estimation was 47% after IBCBT and 37% after dUCBT (p=NS). In multivariate analysis adjusting for statistical differences between 2 groups (such as status of the disease at transplant, age, CMV, previous transplants, GVHD prophylaxis), recipients of IBCBT had improved DFS (HR: 1.64, p=0.035), faster platelet recovery (HR:2.13, p<0.001) and decreased acute GVHD (HR:0.31; p<0.001) compared to dUCBT recipients. We did not find a cut-off value of number of nucleated cells after IBCBT or dUCBT that could be associated with outcomes after both approaches. In conclusion, both strategies have extended the use of CB transplants to adults in need of cord blood transplantation. Therefore, IBCBT is an option to transplant adult patients with single CB units after myeloablative conditioning regimen and may impact the total costs of cord blood transplantation. Based on these results, intra-bone technique may disclose new transplant potentialities also with other HSC sources. Disclosures: No relevant conflicts of interest to declare.

Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematologic malignancies

Blood ◽  
2004 ◽  
Vol 104 (12) ◽  
pp. 3813-3820 ◽  
Author(s):  
Satoshi Takahashi ◽  
Tohru Iseki ◽  
Jun Ooi ◽  
Akira Tomonari ◽  
Kashiya Takasugi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Cord Blood ◽  
Marrow Transplantation ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
Transplant Recipients ◽  
Blood Transplantation

Unrelated cord blood transplantation (CBT) has now become more common, but as yet there have been only a few reports on its outcome compared with bone marrow transplantation (BMT), especially for adults. We studied the clinical outcomes of 113 adult patients with hematologic malignancies who received unrelated BM transplants (n = 45) or unrelated CB transplants (n = 68). We analyzed the hematopoietic recovery, rates of graft-versus-host disease (GVHD), risks of transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. The time from donor search to transplantation was significantly shorter among CB transplant recipients (median, 2 months) than BM transplant recipients (median, 11 months; P &lt; .01). Multivariate analysis demonstrated slow neutrophil (P &lt; .01) and platelet (P &lt; .01) recoveries in CBT patients compared with BMT patients. Despite rapid tapering of immunosuppressants after transplantation and infrequent use of steroids to treat severe acute GVHD, there were no GVHD-related deaths among CB transplant recipients compared with 10 deaths of 24 among BM transplant recipients. Unrelated CBT showed better TRM and DFS results compared with BMT (P = .02 and P &lt; .01, respectively), despite the higher human leukocyte antigen mismatching rate and lower number of infused cells. These data strongly suggest that CBT could be safely and effectively used for adult patients with hematologic malignancies.

Unrelated Cord Blood Cell Transplantation for Acquired Severe Aplastic Anemia: The Report from the Japan Cord Blood Bank Network.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2020-2020
Author(s):  
Seiji Kojima ◽  
Ayami Yoshimi ◽  
Shuichi Taniguchi ◽  
Junichi Hara ◽  
Toshimitsu Matsui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Aplastic Anemia ◽  
Cumulative Incidence ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Bone Marrow Donor ◽  
Grade Ii ◽  
Unrelated Cord Blood

Abstract Treatment approaches for patients with severe aplastic anemia (SAA), who failed immunosuppressive therapy and lack a bone marrow donor remains a great challenge. Unrelated cord blood transplantation (UCBT) has not been recommended for SAA because of historical poor outcome with high rate of engraftment failure. To evaluate the current feasibility of UCBT in SAA, we retrospectively analyzed the outcomes of 31 patients (median age 28 years old; ranged 0.9–72.3 years old) with SAA, who received UCBT as the first graft between 1998 and 2006 in Japan. Median disease duration before UCBT was 337 day (31–5063 days). By serology, HLA loci were matched in 4 recipient-donor pairs and mismatched (1–2 loci) in 27 patients. A minimum cell count of 2 × 107 nucleated cells/kg body weight was infused in all patients. Engraftment was observed in 17 of 24 evaluable patients. The median times to achieve a neutrophil count ≥ 0.5 × 109/l and a platelet count ≥ 50 × 109/l were 19 days (range 12–35 days) and 59 days (range 39–145 days), respectively. The results of chimerism analysis were available in 9 of them and all of them showed complete donor chimerism (&gt;99%) except one with autologous recovery. Late rejection was seen in one patient. Acute GVHD (≥ grade II) was observed in 5 of 18 evaluable patients (grade II; n=4, grade III; n=1) (cumulative incidence =17.1%) and chronic GVHD was observed in 4 of 14 evaluable patients (extensive: n=1, limited: n=3) (cumulative incidence =19.7%). Currently, 13 patients are alive, having survived for median 22.5 months (ranged 3 to 77 months) after UCBT (overall survival at 2 years=40%). Causes of death of 18 patients were following: graft failure (n=7), bacterial/fungal infections (n=3), hepatic veno-occlusive disease (n=3), and others (n=5). The conditioning regimen appeared to be the most important factor for the outcome and low dose total body irradiation (2–4 Gy) + fludarabine (90–250/ mg/m2) and cyclophosphamide (50–100 mg/kg or 2250/mg/m2) (n=5) gave the best outcome with 80% of survival. The GVHD prophylaxis with single agent (cyclosporine or tacrolimus) related with a better engraftment rate than 2 or more agents (84.4% vs 47.3%, p=0.02). These results suggest that UCBT can be a salvage treatment for patients without a bone marrow donor and warrant further evaluation in prospective studies. Optimization of conditioning regimen will improve the engraftment and outcome of UCBT.

High Rate of Engraftment and Low Regimen-Related Toxicity Using Fludarabine, Melphalan and Thiotepa Conditioning for Unrelated Donor Cord Blood Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4414-4414
Author(s):  
Stefan O Ciurea ◽  
Partow Kebriaei ◽  
Issa F Khouri ◽  
Muzaffar H. Qazilbash ◽  
Roy B Jones ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
High Rate ◽  
Unrelated Donor ◽  
Platelet Recovery ◽  
Blood Transplantation

Abstract BACKGROUND: Cord blood transplantation (CBT) represents an alternative source of stem cells for adult patients who lack a matched sibling or unrelated donor. However, the optimal type and intensity of the preparative regimen for patients receiving a CBT is not clear. We hypothesized that a conditioning regimen consisting of fludarabine, melphalan and thiotepa will be associated with an acceptable rate of engraftment and treatmentrelated mortality in patients receiving a CBT. METHODS: 37 patients, median age 31 years (2–57) and a median weight of 73kg, were treated between 8/2003 and 5/2008. All had advanced hematologic malignancies (24 with acute leukemia, 12 with lymphoma and one with CLL) At the time of transplant, 21 pts (57%) were in complete remission (CR) (first CR=20%) and 16 had relapsed/refractory disease. Grafts consisted of double (29 pts) or single (8 pts) CB units. Cytogenetics for patients with acute leukemia were poor in 11, intermediate in 9, good in 1 and unknown in 3 pts. Donor recipient HLA matching was (intermediate resolution class I HLA A and B and high-resolution DRB1): 3/6 (n=1, 1.5%), 4/6 (n=47, 71.2%) and 5/6 (n=18, 27.3%) alleles (n=66 units). Median total nucleated cell count was 1.8×107/kg (range 1–5.8). Nineteen patients received ex-vivo expanded units. The conditioning regimen consisted of melphalan 140 mg/m2 on day -8, thiotepa 10 mg/m2 on day -7, fludarabine 160 mg/m2 over 4 days on days -6, -5, -4, -3, and rabbit ATG 1.25 mg/kg on day -4 and 1.75 mg/kg on day -3 (FMT). Patients with CD 20+ lymphoid malignancies also received rituximab 375mg/m2 on day -9 (n=8, 22%). GVHD prophylaxis was tacrolimus and mini-methotrexate in 23 (62%) and tacrolimus and mycophenolate in 14 pts (38%). RESULTS: 36 patients (97%) were evaluable for engraftment. 1 patient died within 30 days due to progressive leukemia. 34/36 patients (95%) engrafted neutrophils and had hematopoietic recovery with 100% cord blood-derived cells. At day 30, of the 29 patients who received a double CBT, 75% had chimerism derived entirely from one donor while 25% had mixed donors chimerism. Neutrophil recovery to ANC &gt;0.5 × 10e9/l occurred after a median of 21 days (range 6–45) and platelet recovery to &gt;20 × 10e9/l after a median of 37 days (range 26–134, N=24; 67%). 32/37 pts (87%) were in CR after transplant with 16 surviving after a median follow-up of 12.1 months. Thirteen patients (36%) developed gr II–IV aGVHD (gr III–IV aGVHD in 5 patients, 14%), and 13 of 32 patients had cGVHD (40%), with the majority experiencing extensive GVHD. 11 patients (29.7%) relapsed after a median of 7 months post transplant and 12 died of nonrelapse causes. Day-100 treatment-related mortality in this heavily pre-treated population was 10%. Overall, causes of death included disease relapse (n=9), infections (n=6), organ failure (n=3), pulmonary hemorrhage (n=1) and GVHD (n=2). CONCLUSIONS: The FMT regimen was sufficiently immunosuppressive to support high rate of engraftment with acceptable TRM in heavily pre-treated adult patients with advanced hematologic malignancies undergoing CBT. These results support further evaluation of this regimen in CBT.

The Comparative Analysis of Bone Marrow Transplantation and Cord Blood Transplantation from Unrelated Donors in Patients with Myelodysplastic Syndrome in Japan.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2012-2012 ◽  
Author(s):  
Satoshi Takahashi ◽  
Takuhiro Yamaguchi ◽  
Jun Ooi ◽  
Akira Tomonari ◽  
Nobuhiro Tsukada ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Bone Marrow Transplantation ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Calcineurin Inhibitors ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
History Of ◽  
Unrelated Donors

Abstract Background: Allogeneic stem cell transplantation currently is the only potentially curative therapy for myelodysplastic syndrome (MDS). Cord blood and bone marrow from unrelated donors are considered as an acceptable alternative to hematopoietic stem cells. The result of single institutional analysis in Japan has shown cord blood transplantation (CBT) is promising in adults with hematologic malignancies including MDS and is comparable with bone marrow transplantation (BMT) from unrelated or related donors (Blood101: 4711, 2003, Blood104: 3813, 2004, Blood109: 1322, 2007). Objectives: This study aimed to use the data of MDS patients within JMDP and JCBBN registry database to evaluate safety and efficacy of both BMT and CBT from unrelated donors and relate those to biological and procedural factors. Methods: Clinical data of 965 patients with MDS including transformed acute myelogenous leukemia (AML/MDS) who received unrelated BMT (n=532) or unrelated CBT (n=433) between 1993 and 2006 were collected. The median period of follow-up for survivors after BMT was 21 months for BMT and 12 month for CBT, respectively. We analyzed the hematopoietic recovery, incidences of graft-versus-host disease (GVHD), risks of transplant-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. Results: Compared with BMT recipients, CBT recipients were older (52 years old versus 39 years old), included many patients with AML/MDS (58% versus 38%), used many non-myeloablative regimen (55% versus 18%), less human leukocyte antigen-matched donor (3% versus 67%) and less methotrexate (MTX)-containing GVHD prophylaxis (43% versus 91%). Multivariate analysis demonstrated slow neutrophil (P&lt;0.01) and platelet (P&lt;0.01) recoveries in CBT compared with BMT. The incidences of acute and chronic GVHD were not significantly different. Unrelated BMT showed better TRM (25% versus 38% at 1 year, P&lt;0.01), relapse (15% versus 26% at 3 years, P&lt;0.01) and DFS (57% versus 29% at 3 years, P&lt;0.01) results compared with CBT. Next, we analyzed 397 BMT (n=277) and CBT (n=116) recipients who have taken total body irradiation (&gt;8Gy) containing myeloablative regimen and calcineurin inhibitors (cyclosporine or tacrolimus) plus MTX for GVHD prophylaxis without history of prior transplants. In this subpopulation, multivariate analysis revealed no significant difference between BMT and CBT in DFS (59% and 52% at 3 years, respectively). History of chemotherapy before transplant and risk of disease at the transplant were factors affected for DFS results. No statistically difference was also seen in TRM (25% at 1 year after BMT and 24% at 1 year after CBT, respectively). However, the cumulative incidence of relapse was lower in BMT than in CBT (15% and 21% at 3 years, respectively) and this was significantly different by multivariate analysis. Conclusion: The current Japanese registration data showed overall results of unrelated BMT were better than those of unrelated CBT in MDS. These data also suggest that unrelated CBT could be safely and effectively used for patients with MDS as unrelated BMT when adequate transplant procedures are selected. Myeloablative conditioning regimen including TBI and calcineurin inhibitors plus MTX for GVHD prophylaxis might be promising and the results of prospective clinical studies are warranted.

Post-Transplantation Cyclophosphamide (PT-CY) After Myeloablative Conditioning Regimen (MAC) In Unmanipulated Haploidentical Bone Marrow Transplantation (hBMT) Is Highly Effective As Gvhd Prophylaxis and Disease Free Survival In Pediatric and Adult Patients With High Risk Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4576-4576
Author(s):  
Maria Domenica Simone ◽  
Anna Proia ◽  
Alessandro Severino ◽  
Alison Shardlow ◽  
Novella Natale ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Conditioning Regimen ◽  
Marrow Transplant ◽  
Adult Patients ◽  
High Rate ◽  
Myeloablative Conditioning ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Disease Free

Introduction BMT from HLA haploidentical family members (hBMT), using either T-cell depleted or T-cell replete grafts, is increasingly employed in patients who urgently need (but lack) a donor. After the promising results in hBMT obtained by the Baltimore group (Luznik et al., Biol Blood Marrow Transplant 2008, Blood 2010) introducing post-transplant high-dose cyclophosphamide (PT-CY) following a non-myeloablative conditioning regimen, the Genoa group (Raiola et al., Biol Blood Marrow Transplant 2013) has shown, in the haploidentical setting that a myeloablative conditioning (MAC) with PT-CY (on day +3 and +5), cyclosporine from day zero and mycophenolate mofetil (MMF) from day +1, is associated with a high rate of engraftment, acceptable TRM and GVHD, and induces durable remission with low incidence of relapse in a high proportion of patients with high-risk hematologic malignancies. We now report a series of 13 heavly pretreated high-risk leukemia patients who underwent a MAC protocol consisted of TBF regimen: Thiotepa (10 mg/kg), Busulfan (9,6 mg/kg) and Fludarabine (150 mg/mq). As graft versus host disease (GVHD) prophylaxis, 2 patients received a 5 drugs combination (ATG-Fresenius, CSA, MTX, MMF and Basiliximab) and stem cells source was G-CSF-primed haploidentical bone marrow (hBM) cells (Di Bartolomeo et al., Blood 2013). In 11 patients stem cells source was non-primed unmanipulated hBM cells, and GVHD prophylaxis consisted of PT-CY (50mg/kg) iv on day +3 and +4, CSA 2.5 mg/kg/day and MMF 45 mg/kg/day from day +4. Results From 2008 to 2013, 11 adult patients (M/F=8/3; median age 40 years, range 23 to 62) and 2 pediatric patients (M/F=1/1, age 4 and 7 years) with high risk ALL (1 pediatric; 2 adult), AML (1 pediatric; 8 adults) and one Richter evolution of CLL, underwent T replete hBMT. At time of transplant 10 patients were in CR (CR1=9, CR2=1), 1 in a good PR and 2 had refractory disease. Grafts contained a median of 5.68 x 108/kg nucleated BM cells (range 0.7-62.1), 2.14x106/kg CD34+ cells (range 0.55-7.09) and 34.7x106/kg CD3+ cells (range 16-93.4). 12 patients are evaluable for engraftment. This occurred in 100% for neutrophils and 93% for platelets, with a median time to neutrophil recovery (> 0.5 x 109/L) of 22.5 days (range, 13-40) and to platelet recovery (> 20.0 x 109/L) of 27.5 days (range, 17-49). All patients had full donor chimerism by day +30. Non relapse mortality (NRM) was 23%: 2 pt died for sepsis (one before engraftment), 1 for aGVHD. 4 patients had grade I and 3 grade II aGvHD, respectively. Only one patient had a grade III, and another had grade IV fatal GVHD. 3 patients had only limited chronic GvHD. Up to now, only 3 patients have relapsed and of these 2 have died. 8 patients (61.5%) are currently surviving, 7 of them are disease-free with median follow-up time of 165 days (range 32-896 days) from transplant. Conclusion Our preliminary results confirm that haplo-BMT following a MAC regimen, is a feasible treatment in pediatric and adult patients, and that PT-CY is highly effective as GVHD prophylaxis, producing a high rate of stable engraftment with encouraging non relapse mortality and relapse-free survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Combination of a Cyclophosphamide-Total Body Irradiation Conditioning Regimen and Tacrolimus Plus Mycophenolate Mofetil for Gvhd Prophylaxis Is Associated with Higher HHV-6 Encephalitis Incidence after Cord Blood Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1986-1986
Author(s):  
Takuto Mori ◽  
Nobuhiro Hiramoto ◽  
Ryosuke Ueda ◽  
Yoshimitsu Shimomura ◽  
Satoshi Yoshioka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Cord Blood Transplantation ◽  
Cell Number ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Conditioning Regimens ◽  
Total Body

Background Human herpesvirus-6 (HHV-6) encephalitis occurs frequently through cord blood transplantation (CBT), and leads to a high risk of mortality and morbidity. Although CBT is a known risk factor for HHV-6 encephalitis, a thorough analysis of risk factors for HHV-6 encephalitis in patients receiving CBT has not been performed, and several risk factors remain unidentified. In our center, generally, either tacrolimus (Tac) plus methotrexate (MTX) (Tac/MTX) or mycophenolate mofetil (MMF) (Tac/MMF) was selected for graft-versus-host disease (GVHD) prophylaxis after CBT, at the physician's discretion. However, in recent years, Tac/MMF became the standard choice. We observed that the incidence of HHV-6 encephalitis tended to be markedly higher among patients receiving treatment with a cyclophosphamide (Cy) and total body irradiation (TBI) (Cy/TBI)-based regimen and Tac/MMF after CBT. Therefore, we aimed to ascertain whether certain conditioning regimens and GVHD prophylaxis regimens are associated with the occurrence of HHV-6 encephalitis after CBT. Methods In this retrospective study, we examined 103 patients undergoing CBT for hematological diseases at our center between 2011 and 2019. To analyze the effect of GVHD prophylaxis on the occurrence of HHV-6 encephalitis, we divided patients into two groups based on the GVHD prophylaxis regimen used: the Tac/MTX group and the Tac/MMF group. We excluded one patient who received Tac alone and one who received cyclosporine plus MTX. Finally, 101 patients were enrolled. Routine peripheral blood examinations for HHV-6 were performed once or twice a week. HHV-6 encephalitis was defined as the presence of a central nervous system dysfunction, along with a positive polymerase chain reaction result for HHV-6 DNA in the cerebrospinal fluid. HHV-6 viremia was defined as the presence of HHV-6 in the peripheral blood. Results The median age of patients was 47 years, and the median follow-up duration for surviving patients was 432 days. Conditioning regimens included myeloablative conditioning (MAC, n=64) and reduced-intensity conditioning (RIC, n=37). MAC included Cy/TBI-based regimens in 42 patients and fludarabine (Flu) plus busulfan (Bu) (Flu/Bu)-based regimens in 23, and RIC included Flu plus melphalan-based regimens in 34 patients and other regimens in 2. Sixty-four patients received Tac/MMF as GVHD prophylaxis, whereas 37 received Tac/MTX. Six patients received HLA-matched (6/6) cord blood (CB), 27 received HLA one-antigen mismatched CB, and 68 received HLA two-antigen mismatched CB. The median total nucleated cell number and CD34-positive cell number at cryopreservation were 2.2 × 107/kg and 0.7 × 105/kg, respectively. Thirteen patients (12.8%) experienced primary graft failure. Overall, the cumulative incidence of HHV-6 viremia on day 40 was 68%, and the median time from CBT to HHV-6 viremia was 23 days. The cumulative incidence of HHV-6 viremia was significantly higher in the Tac/MMF group than in the Tac/MTX group (Tac/MMF group, 75%; Tac/MTX group, 56%; p=0.03). Ten patients developed HHV-6 encephalitis. Overall, the cumulative incidence of HHV-6 encephalitis on day 60 was 10.1%. The cumulative incidence of HHV-6 encephalitis tended to be higher in the Tac/MMF group than in the Tac/MTX group (14.1% vs. 2.7%, respectively; p=0.08). Therefore, the administration of Tac/MMF as GVHD prophylaxis after CBT was identified as a probable risk factor for HHV-6 encephalitis, and we sought to identify more such risk factors, specifically among patients receiving Tac/MMF. In the analysis of Tac/MMF group, the cumulative incidence of HHV-6 encephalitis was significantly higher among patients receiving Cy/TBI-based regimens than among those receiving other regimens (35.7% vs. 8.1%, respectively; p<0.01) (Fig. 1a). In addition, among the entire group of patients receiving Cy/TBI-based regimens, the cumulative incidence of HHV-6 encephalitis was significantly higher in the Tac/MMF than in the Tac/MTX group (35.7% vs. 0%, respectively; p<0.01) (Fig. 1b). Conclusion Our analysis showed that patients receiving Tac/MMF as GVHD prophylaxis after CBT with a Cy/TBI-based regimen have a significantly higher risk of developing HHV-6 encephalitis. Further studies using a large cohort are required to elucidate the association between the occurrence of HHV-6 encephalitis and the use of Tac/MMF in patients undergoing CBT with a Cy/TBI-based regimen. Disclosures No relevant conflicts of interest to declare.

Double Umbilical Cord Blood Transplantation with Reduced Intensity Conditioning and Sirolimus-Based GVHD Prophylaxis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2016-2016 ◽  
Author(s):  
Corey Cutler ◽  
Rachel Mitrovich ◽  
Grace Kao ◽  
Vincent Ho ◽  
Edwin Alyea ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity

Abstract Umbilical cord blood (UCB) is an alternative stem cell source for patients without related or unrelated donors. Single-unit UCB transplantation in adults is associated with high transplant-related mortality, largely due to delayed engraftment and infection. While double umbilical cord blood transplantation (DUCBT) is associated with faster engraftment, it is also associated with high rates of acute GVHD. We studied DUCBT using sirolimus and tacrolimus as GVHD prophylaxis to improve GVHD outcomes. Methods: Reduced-intensity conditioning consisted of fludarabine (30mg/m2×6 days), melphalan (100mg/m2× 1day), and rabbit ATG (1.5 mg/kg × 4 days). Cord blood units were ≥4/6 HLA-A, B, DR allele-matched with each other and the recipient, and contained a minimum combined dose of 3.7× 107 TNC/kg (pre-cryopreservation). GVHD prophylaxis consisted of tacrolimus (serum conc. 5–10 ng/ml) and sirolimus (serum conc. 3–12 ng/ml). Filgrastim was used routinely after transplantation, and subjects received prophylactic anti-fungal antibiotics as part of routine supportive care. Results: 27 patients (median age 49 years, range 19–67) with &gt;100 day follow-up are reported. Diagnoses include AML(8), NHL(7), HD(4), MDS(3), CLL/PLL(2), ALL(1), MPD (1) and CML(1). The median total cell doses prior to cryopreservation were 5.25 ×107 TNC/kg (range 3.74–7.58 ×107) and 12.57 ×106 CD34+ cells (range 1.45–29.0 ×106). Neutrophil engraftment occurred at a median of 21 days (range 13–70) and platelet engraftment to 20 000/μL occurred at a median of 42 days (range 25–162) after DUCBT. Three subjects did not attain platelet transfusion independence by day 100 and there were 2 late graft failures. 3 patients developed Gr II–IV acute GVHD (2 Gr. II and 1 Gr. III). The rate of acute GVHD was lower when compared with a prior cohort that received the identical conditioning regimen, but with cyclosporine and MMF as GVHD prophylaxis (11.1% vs. 37.7%, p=0.05). 2 patients developed chronic GVHD at a median of 203 days from transplantation. The median follow up is 12 months (15 months among survivors, range 4–20 months). 100-day treatment-related mortality was 11.1%. There was no VOD or TMA. Relapse-free and overall survival at 1 year are 54.4% and 72.9% respectively. Causes of death include sepsis(4), relapse(2), and EBV-associated PTLD(2). Chimerism analysis at day 100 (n=22) revealed complete single cord chimerism in 13 subjects with mixed cord chimerism in 9. The first infused unit was the predominant unit at day 100 in 14/22 subjects. There was no correlation between cord dominance and HLA match, TNC/kg or CD34+ cell count prior to cryopreservation. Conclusions: This study demonstrates excellent engraftment after DUCBT in adult recipients after a reduced-intensity conditioning regimen. The risk of acute and chronic GVHD is low when sirolimus and tacrolimus are used as GVHD prophylaxis when compared with our prior experience with cyclosporine and MMF, and survival is comparable to historical unrelated donor cohorts.

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