Unrelated Cord Blood Does Not Increase An Overall Risk Of Invasive Fungal Infections Compared To Unrelated Bone Marrow: A Single Center Retrospective Analysis For 749 Recipients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4541-4541 ◽  
Author(s):  
Yuki Asano-Mori ◽  
Hideki Araoka ◽  
Muneyoshi Kimura ◽  
Daisuke Kaji ◽  
Hikari Ota ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Systemic Corticosteroids ◽  
Grade Ii ◽  
Unrelated Cord Blood

Background Invasive fungal infections (IFIs) are of great concern after allogeneic hematopoietic stem cell transplantation (HSCT), the risk of which is considered to be particularly prominent among cord blood transplantation (CBT) recipients. Patients and Methods We retrospectively analysed the records of 749 adult patients who underwent CBT or unrelated bone marrow transplantation (uBMT) for the first time at the Toranomon Hospital between 2002 and 2012, and who had neither prior history nor suspicious findings of IFIs. As prophylaxis for IFIs, fluconazole (FLCZ) or itraconazole (ITCZ) capsules were conventionally used until around 2006, which were then changed to newer mold-active agents including ITCZ oral solution, voriconazole or micafungin after their approval in Japan, the choice of which was subjected to physician's discretion. Results Engraftment achieved in 418 CBT patients and 198 uBMT patients with a significantly longer neutropenic period in CBT patients (median 20 days vs 18 days, P<0.001), whereas 37 patients underwent re-transplantation and 96 died before engraftment. The incidences of grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were significantly less frequent after CBT compared to uBMT (40% vs 54% and 17% vs 46%, both P<0.001). Systemic corticosteroids at ≥0.5mg/kg/day was given in fewer CBT patients compared to uBMT patients (59% vs 66%, P=0.07). The median durations of immunosuppressants and antifungal prophylaxis were significantly shorter in CBT patients compared to uBMT patients (118 days vs 302 days and 315 days vs 491 days, both P<0.001). As prophylaxis for IFIs, 194 CBT patients and 91 uBMT patients received FLCZ/ITCZ capsules, while 341 CBT patients and 123 uBMT patients received newer mold-active agents. Seventy-nine patients (57 in CBT and 22 in uBMT) developed IFIs with a cumulative incidence of 12.2%, at a median of 27 (1-1646) days after HSCT. About 60% of the patients developed IFIs by day 50 and the percentage reached more than 90% until 1 year. The median onset was significantly earlier in CBT patients compared to uBMT patients (day 19 vs day 61, P=0.007). The cumulative incidence of IFIs was significantly higher in CBT patients compared to uBMT patients during 50 days after HSCT (7.9% vs 3.8%, P=0.04), but became significantly lower thereafter until 1 year (2.7% vs 6.9%, P=0.02), and an overall incidence was almost similar between the 2 groups (12.6% vs 11.6%, P=0.58) (Figure 1). Four patients had 2 infectious episodes caused by different fungal species, and a total of 83 infectious episodes were documented. Eighty-one cases were breakthrough infection during antifungal prophylaxis (FLCZ/ITCZ capsules in 28, and newer mold-active agents in 53). Invasive aspergillosis (IA) was the most common, accounting for 67.9% (proven in 11, probable in 46), followed by invasive candidiasis (IC), (19.3%; candidemia in 15, encephalitis in 1). Although the incidences of IA and IC were comparable between CBT and uBMT patients, relatively rare type of IFIs caused by Trichosporon (4 cases), Mucor (2 cases) and Rodotorula (1 case) exclusively occurred in CBT patients, except one case of Fusarium infection in a patient who relapsed after uBMT. Grade II-IV acute GVHD, extensive chronic GVHD and systemic corticosteroids at ≥0.5mg/kg/day were identified as significant risk factors of IFIs for both groups (HR 1.89, P=0.01, HR 4.16, P=0.006, and HR 1.83, P=0.02). However, the impact of all these were not apparent in CBT patients (HR 1.59, P=0.16, HR 2.18, P=0.29 and HR 1.48, P=0.22), in contrast with the powerful impact in uBMT patients (HR 2.51, P=0.049, HR 10.23, P=0.03 and HR 2.87, P=0.03). Although the cessation of antifungal prophylaxis significantly increased the risk of IFIs in uBMT patients (HR 5.95, P=0.01), it showed no impact in CBT patients (HR 0.87, P=0.89). IFIs were main causes of death in 21 patients, which significantly affected non-relapse mortality in both CBT and uBMT patients (HR 3.93 and HR 6.08, both P<0.001). Conclusion Unrelated cord blood did not increase an overall incidence of IFIs, because higher risk in the early post-transplant period was counterbalanced by the dramatically decreased risk due to lower frequencies of GVHD and its treatment in the later period. Particular attention might be required to the early-onset IFIs due to fungi other than Aspergillus or Candida species, in order to further decrease the risk of IFIs after CBT. Disclosures: No relevant conflicts of interest to declare.

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.

Acute Graft Versus Host Disease (GVHD) Is Increased in Patients Receiving Cyclosporine/Cellcept as Frontline Prophylaxis Against GVHD in Pediatric Patients Undergoing Allogeneic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2896-2896
Author(s):  
Sonali Lakshminarayanan ◽  
Paul Szabolcs ◽  
Vinod Prasad ◽  
Suhag Parikh ◽  
Susan Wood ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Oral Therapy ◽  
Pediatric Patients ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Grade Ii ◽  
Unrelated Cord Blood ◽  
Related Bone Marrow

Abstract Traditionally, pediatric patients are prophylaxed against GvHD with cyclosporine (CSA) plus either methotrexate (Mtx) or methylprednisolone (Pred). Mtx worsens the severity of mucositis and renal insufficiency while pred causes muscle wasting, hypertension, hyperglycemia and increased infections. Cellcept (myophenolic acid) is a better tolerated, less toxic agent with synergistic immunosuppressive effects when combined with cyclosporine or tacrolimus. We explored its use in combination with cyclosporine in 63 pediatric patients (49% male, 74% Caucasian, 36% CMV+) undergoing allogeneic transplantation. Patients with both malignant (n=24) and non-malignant (n=39) conditions ranging in age from 2 weeks to 26 years were transplanted after myeloablative preparative regimens with either related bone marrow or cord blood (n=11) or unrelated cord blood (n=52), using cellcept and cyclosporine for GVHD prophylaxis. Cellcept and CSA were administered intravenously through the first 40–60 days post transplant using cellcept at a dose of 15mg/kg/dose IV q8H beginning on day -2 or -3 and CSA in traditional fashion targeting trough levels of 200–450 (infusion) and 150–350 with intermittent dosing. The patient then transitioned to oral therapy at the same dose and schedule until day 100–180 for cellcept and day 270 for cyclosporine and then tapered if no active GVHD was present. There were no acute toxicities attributable to cellcept observed in patients on IV or oral therapy. Despite the lack of steroids in the GVHD prophylactic regimen, all patients required treatment with antihypertensive therapy. Grossly, infection rates did not vary from those previously observed in conventionally treated patients at our center. The cumulative incidence (CINC) of neutrophil engraftment by day 42 was 79.4% (95% CI 64.7–91.2) which is comparable to previous reports. Two patients engrafted after a second unrelated cord blood transplant. Of the six patients who did not engraft, 3 died of infectious complications, two died of VOD and multi-system organ failure and one died of congenital pulmonary hypertension. Of the 59 patients evaluable for GVHD, follow-up ranged between 52 and 994 days (median 224 days). The CINC of acute GVHD grades II–IV by day 100 was 64.1% (95% CI 47.8–82.1) and the CINC of acute GVHD grades III– IV by day 100 was 6.3% (95% CI 0–17.0). Follow-up is too short to comment on the incidence of chronic GvHD, but to date, 5 of 14 patients followed for >100 days have developed mild chronic GvHD. The incidence of grade II acute GVHD was higher than that previously reported in pediatric patients receiving CSA/Pred while the incidence of grade III–IV GVHD was comparable. While this data is early, it appears that the incidence of acute Grade II GVHD is increased compared to previous series in patients treated with cellcept instead of Mtx (related bone marrow transplantation) or pred (unrelated cord blood transplantation). Engraftment in UCBT recipients was not compromised with the use of IV cellcept administered in the peritransplant period. Overall, despite the use of steroids to treat aGVHD, there was overall steroid sparing with this regimen. Additional patients will need to be tested with this regimen and longer follow-up is necessary to fully define the risks or benefits of this therapy.

Outcomes after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia. An Eurocord-Netcord Survey.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 304-304 ◽  
Author(s):  
Vanderson Rocha ◽  
Gerard Michel ◽  
Nabil Kabbara ◽  
William Arcese ◽  
Juan Ortega ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Advanced Phase ◽  
Unrelated Cord Blood

Abstract Unrelated cord blood transplantation (UCBT) is an alternative option to treat children with haematological diseases without an HLA-identical donor. We have analyzed a total of 323 children with ALL receiving an UCBT, from 1994 to 2004 in 99 transplant centres in 24 countries, mostly in Europe. Cumulative incidence with competing risk and KM estimates were used to calculate outcomes. Seventy six children were transplanted in CR1, 136 in CR2 and 111 in more advanced phase of the disease. Among those children poor cytogenetics were observed in 89% of children in 1CR, 33% in 2CR and 42% in advanced phase. Twenty percent of children transplanted in advanced phase had been previously autografted. The median age was 6.5 years at UCBT, median cell dose infused was 4.1x107/kg and the median follow time was 22 months (3–96). The cord blood was HLA identical (6/6) in 12% of the cases, 5/6 in 46%, 4/6 in 39% and 3/6 in 3%. All children received myeloablative conditioning regimen (TBI in 66%) and the majority (67%) received CsA+corticoids as GVHD prophylaxis. Cumulative incidence of neutrophil recovery at day 60, platelets recovery (&gt;20.000) at day 180, acute (grade II–IV) and chronic GVHD were 76±5%, 54±5%, 42±3%, 14±2%, respectively. Overall 2 year-LFS was 36±3%. In a multivariate analysis, only CR1 or CR2 were associated with better LFS (HR=1.8; p&lt;0.0001). Outcomes CR1 (n=76) CR2 (n=136) Advanced (n=111) TRM at day 100 22+/−5% 25+/−4% 34+/−5% Relapse at 2 years 34+/−8% 37+/−5% 48+/−7% LFS at 2 years 42+/−6% 41+/−4% 24+/−4% For those patients transplanted with poor cytogenetics, LFS at 2 years was 32±6% and it was 37% for CR1, 43% for CR2 and 0% for advanced phase of the disease. In conclusion, in these large series of high risk ALL patients, these results show that UCBT should be proposed as alternative source of allogeneic transplantation for children lacking an HLA identical donor, in earlier status of the disease.

Mutant TIRAP Gene Polymorphism Is Associated with Outcomes in HLA Genoidentical Bone Marrow Transplants Recipients with Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 327-327 ◽  
Author(s):  
Vanderson Rocha ◽  
Raphael Porcher ◽  
Nabil Kabbara ◽  
Regis Peffault de Latour ◽  
Marie Robin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Fungal Infection ◽  
Lower Incidence ◽  
Cumulative Incidence ◽  
Gene Polymorphisms ◽  
Acute Gvhd ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Adaptor Protein

Abstract Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein TIRAP, mediates downstream signaling of TLR2 and TLR4. A leucine (Leu) substitution at position 180 serine (Ser) of TIRAP was shown to protect from infections. We hypothesized that the incidence of infections and outcome after bone marrow transplantation (BMT) could be influenced by the TIRAP gene polymorphisms. Genotyping for TIRAP at Ser180 was performed in 107 donor/recipients pairs: 64% of recipients and 63% of donors were homozygote wild type (wt) Ser180/Ser180, 20% and 19% were Ser180/Leu180 and 17% and 18% Leu180/Leu180. Severe bacterial (pneumonia, septicemia and septic shock), viral or invasive fungal infections during 180 days after BMT, TRM (transplant related mortality), acute GVHD and survival were studied retrospectively. An allogeneic HLA-identical BMT was performed in 107 patients (median age was 35 years), with acute (n=39) or chronic Leukemia (n=68). Conditioning regimen consisted of Busulfan+Cyclophosphamide±others (BU-CY) in 73 (68%) patients and TBI+CY in 15 (14%) or TBI+Melphalan in 17 (16%). GVHD prophylaxis consisted of CsA+MTX in 94%. Median follow-up time was 77 months (18–147). Cumulative incidence of neutrophil recovery was 94%. Acute GVHD (II-IV) was observed in 42%, and chronic GVHD in 50 out of 98 at risk. Estimate 5-year survival was 54%. The cumulative incidence of any first infection by day 180 was 56%, being 28% for at least one bacterial infection, 39% for viral infection and 12% for invasive fungal infection (8 invasive aspergillosis, 4 disseminated candidiosis and 1 disseminated Malassezia furfur fungal infection). TRM cumulative incidence at 1 year was 35%. Recipient’s TIRAP gene polymorphisms were not associated with outcome. However, patients transplanted from a mutant TIRAP donor (Leu/Ser or Leu/Leu) had a trend to lower incidence of fungal infections (p=0.08); lower incidence of acute GVHD (p=0.03), decreased TRM (p=0.02) and improved overall survival (p=0.02). In a multivariate analysis, adjusting for other prognostic factors, TIRAP donor polymorphisms were associated with decreased TRM (HR=0.49, p=0.02): TRM at 1 year was 43% when donors were wt (Ser/Ser) as compared to 20% when donors were mutants. There was also a trend to decreased incidence of acute GVHD in patients with a mutant TIRAP donor as compared to the others (30% versus 49%; HR 1.88 p=0.06) and better overall survival (67% versus 44%, respectively HR 1.82; p=0.07). Recipients of bone marrow (BM) from wt TIRAP donors seemed to die more frequently from infection (1 yr cumulative incidence 21% vs 8%, p=0.07). In conclusion, the presence of a Leu substitution at position 180 in the TIRAP gene of BM donors decreases the incidence of TRM in HLA-identical BMT, probably reflecting better immune reconstitution and protection against infections. This finding can help defining better surveillance and prophylaxis of bacterial infections in BMT recipients from donors with the wt TIRAP (Ser/Ser) genotype.

Complementary Transplantation with Haploidentical Stem Cells and Unrelated Cord Blood for Leukemia and Thalassemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1235-1235
Author(s):  
Chunfu Li ◽  
Yuelin He ◽  
Xuedong Wu ◽  
Xiaoqin Feng ◽  
Jianyun Liao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Mixed Chimerism ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Unrelated Cord Blood ◽  
Kinetics Of

Abstract Background Unrelated Cord Blood (UCB) Transplantation is a potentially curative therapy for leukemia and thalassemia; however, engraftment failure and slow immune reconstitution remain key clinical issues. We hypothesized that complementary transplantation (CT) of UCB with haploidentical stem cell graft (hap-SC) tolerized with post-transplant cyclophosphamide would result in rapid engraftment and low relapse rate without additional risk of graft-versus-host disease (GVHD). Therefore, we developed a novel complementary transplant approach. Patients and Method Sixty-six patients received CT between December 2012 and June 2016. Of them, 30 patients had malignance diseases (MD), including 11 lymphoid and 19 myeloid diseases, and 36 had thalassemia major (TM). Median age was 12 (range; 2-13) and 8 (3-17) years in the MD and TM group, respectively. Median follow-up time was 13 (7-32) and 19 (2-25) months, respectively. Conditioning (Regimen CT-13) included Cyclophosphamide on day-8 to -7, Busulfan on day-6 to -4, Fludarabine on day-6 to -2 and Thiotepa on day-3. Hap-SC was infused on day 0. GVHD prophylaxis consisted of Cyclophosphamide on day+3 to +4. UCB was infused on Day+6. Mycophenolate mofetil and Tacrolimuswas started on day+6 for GVHD prophylaxis. For 26 TM patients transplanted since 2014, they received identical regimen except with the additional Thymoglobulin on day -11 to -9 (Regimen CT-14). Results The chimerism status at last follow-up was Hap-SC, UCB, mixed stem cells (MSC) and rejection in 20, 9, 1 and 0 patient in the MD group; and 16, 14, 3 and 3 patients in the TM group. Interesting, the initial chimerism on day+28 in the TM group was Hap-SC, UCB and MSC engrafted in 15, 7 and 12 patients, respectively. Thus, the MSC was not stable in TM patients; UCB typically became dominant overtime instead of the initial majority from hap-SC (Fig. 1). In the MD group, the time to neutrophil >= 0.5x109/L, platelet >=20 x109/L and hemoglobin >=80 g/L was day+18 (14-36), +10.0 (6-51) and +7 (1-20) in the final hap-SC engrafted group; and+30 (22-35), +25 (1-64) and +7 (3-28) in the final UCB engrafted group. Overall survive (OS), disease-free survive (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were 75.6%, 64.3%, 24.7£¥ and 13.7%, respectively, in all 30 MD patients; and 79.3%,73.8%,15.5% and 12.3% (Fig.2), respectively, in the 25 cases with complete remission (CR) at the time of transplantation. The corresponding data were 89% vs. 88.9%£¬65.0% vs. 77.8%£¬31.1 % vs.12.5% and 10.3% vs.11.1%£¨p>0.05 in all pairs), respectively, in hap-SC and UCB engrafted groups. Donor carrying KIR centromeric B motif was associated with reduced RI (10 % vs. 33.9%). In TM group, OS, thalassemia free survive (TFS), rejection and transplant-related mortality were 91.2%, 85.7%, 5.6% and 8.8%, respectively in all 36 patients. Impressively, all of the 26 patients who received the newer CT-14 protocol were alive without TM (Fig. 2). 7/10 UCB carrying KIR centromeric B motif engrafted. In the MD group, 23.3% had grade II-IV and10.0% had III-IV acute GVHD. Grade II, III and IV acute GVHD occurred in 3 patients, respectively, in TM group. One MD patient had severe chronic GVHD (lung) after DLI for relapse. No moderate chronic GVHD occurred in TM groups. Summary The CT-13 regimen resulted in high OS and DFS, especially in CR patients in the MD group. The CT-14 leaded to 100% TFS in thalassemia patients. Acute and chronic GVHD were acceptable. Donor carrying centromeric B motif promoted engraftment and reduced RI. A multicenter study should be developed in the future based on our favorable results. Figure 1. Kinetics of mixed chimerism in thalassemia patients Figure 1. Kinetics of mixed chimerism in thalassemia patients Figure 2. Results of malignance diseases in CR status at the time of transplant Figure 2. Results of malignance diseases in CR status at the time of transplant Figure 3. Thalassemia-free survive resulted from regimen CT-14 Figure 3. Thalassemia-free survive resulted from regimen CT-14 Disclosures No relevant conflicts of interest to declare.

Outcomes of Cord Blood Transplantation from an HLA-Identical Sibling for Patients with Inherited or Acquired Bone Marrow Failure Disorders: A Report from Eurocord, Cord Blood Committee (CBC-CTIWP) and Severe Aplastic Anemia Working Party (SAAWP) of the European Group of Blood and Bone Marrow Transplantation (EBMT)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 153-153
Author(s):  
Simona Pagliuca ◽  
Régis Peffault de Latour ◽  
Franco Locatelli ◽  
Jean-Hugues Dalle ◽  
Kim Vettenranta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Median Time ◽  
Graft Failure ◽  
Bone Marrow Failure ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Sibling Donor ◽  
Blood Transplantation ◽  
Grade Ii

Abstract Bone marrow failure (BMF) syndrome is a group of rare hereditary or idiopathic disorders occurring at all ages. For BMF patients under 40 years of age and having an HLA-identical related donor, allogeneic bone marrow transplantation (HSCT) is indicated. The use of cord blood transplantation (CBT) from an HLA-identical sibling donor is of interest in non-malignant disease due to the low risk of graft-versus-host disease (GVHD) associated with this type of stem cell source and the absence of risk to the donor. We analyzed outcomes of 122 children and young adults with inherited or acquired BMF syndrome, who received a CBT from an HLA-identical related donor. Patients were transplanted in EBMT centers between 1988 and 2014 and reported to Eurocord and EBMT. Ninety-six patients had an inherited and 26 patients had an acquired BMF. The specific diagnosis were: Fanconi anemia (n=48), Diamond Blackfan anemia (n=25), Amegakariocytic thrombocytopenia (n=6), Kostmann syndrome (n=4), Dyskeratosis congenital (n=3), Schwachman-Diamond syndrome (n=2), and unclassified inherited BMF (n=8) for the inherited group and severe aplastic anemia (n=25), pure red cell aplasia (n=1) for the acquired group. Eighty-nine patients received a single cord blood (CB) unit, whereas 33 patients received a combination of CB and bone marrow (BM) cells from the same sibling donor. The main reason for adding BM was due to the low cell dose of the single CB unit alone. Of patients receiving CB+BM, 6 had an acquired and 24 had an inherited BMF. Median age at CBT was 6.7 (range 1-16) years (5.6 years for patients with acquired and 6.9 years for those with inherited BMF). Median interval between diagnosis and CBT was 21 (range 2-114) months for the acquired and 55 (range 2-160) months for the inherited group, respectively. Fifty-nine patients (53%) received a reduced intensity conditioning (RIC) and 52 (47%) were treated with myeloablative regimens (MAC) (data available for 111 of 122 patients). Fludarabine-based regimens were used in 54 patients (44%). For patients receiving a RIC the most common regimen was cyclophosphamide and fludarabine (56%), and for MAC, cyclophosphamide and busulfan (46%). Total body irradiation was used in 8 patients (both in RIC and MAC settings). GVHD prophylaxis consisted mainly of cyclosporine alone (CSA) in 53 patients (43%), CSA + micophenolate mofetil in 11 patients (9%) and CSA + methotrexate in 23 patients (19%). The median number of total nucleated cells (TNC) infused was 6.2x107/Kg (1-24.2x107/Kg) for patients receiving a single CB unit and 26.8x107/Kg (5.3-41x107/Kg) for those receiving CB+BM (median TNC was 3x107/Kg in CB, and 22x107/Kg in BM graft). Median follow up is 5 (range 0.6-25) years. The cumulative incidence (CI) of neutrophil recovery at day 60 was 91%+9%, and the median time to engraftment was 21 (range 7-100) days. The CI of platelets engraftment at day 180 was 89+3% with a median time of 35 (range 7-138) days. Thirteen patients experienced primary graft failure (PFG) (12 patients after a single CB and one after a CB+BM graft). For those patients with available information, treatment of graft failure was second BM-HSCT (n=6), and growth factors (n=1). Of the 13 patients with graft failure, 11 died within in a median time of 1.9 (0.3 to 6) months after CBT. Two patients are alive after the second HSCT. The 100-day CI of grade II-IV acute GVHD was 11+3% (15 patients: grade II, n=8; grade III, n=6; grade VI, n=1), and the 1-year CI of chronic GVHD was 12+4%. The 1-year CI of transplant-related mortality was 13+3%, 17 patients died: 11 due to PGF (infections (n=6) hemorrhagic syndrome (n=1) and other causes (n=4)) and the remaining 6 of acute respiratory distress syndrome (n=1), and infections (n=5). Five-year overall survival (OS) for the whole population was 87+3%. OS was 80+8% for patients with acquired BMF, 87+3% for Fanconi anemia patients, 95+4% for those with Diamond Blackfan, and 86+7% for other inherited BMFs. In pediatric and young adult patients with either inherited or acquired BMF syndrome, CBT from an HLA-identical sibling donor is associated with excellent long-term outcomes with particular low rates of both acute and chronic GVHD, this latter observation being of particular importance for patients with non-malignant disorders. In case of inherited BMF, collecting cord blood unit at the birth of a new sibling is strongly recommended. Disclosures Dufour: Pfizer: Consultancy.

Similar Survival, but Better Quality of Life After Myeloablative Transplantation Using Unrelated Cord Blood Versus Identical Sibling Hematopoietic Cells in Adults with Hematologic Malignancies: A Single Institute Analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3134-3134
Author(s):  
Huilan Liu ◽  
Liangquan Geng ◽  
Xingbing Wang ◽  
Kaiyang Ding ◽  
Juan Tong ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem ◽  
Similar Survival ◽  
Unrelated Cord Blood

Abstract Abstract 3134 HLA-identical sibling allogeneic hematopoietic stem cell transplantation (HSCT) is the best therapeutic option for high-risk hematological disease, but it is limited by lack of availability of a suitable donor for most candidate patients. At our institution our center, unrelated cord blood transplantation (UCBT) was used as the first alternative option for patients who lack an HLA-matched related donor in the last decade. We retrospectively analyzed the clinical outcomes of UCBT versus HLA-identical sibling HSCT for adult patients with hematologic malignancies. Between April 2000 and May 2012, 194 consecutive adult patients with malignant hematological diseases received UCBT (77 patients; median age 21y, r 14–46; male 49) and related bone marrow transplantation (BMT) and/or peripheral blood stem cells transplantation (PBSCT) (117 patients; median age 30y, r 14–53; male 75). Diagnoses in two groups (UCBT/Sibling) included de novo AML (n = 23/32), ALL (n = 30/26), CML (n = 17/47), MDS/AML (n = 3/8), mixed phenotype acute leukemia (MPAL) (n = 3/1), NHL (n = 1/2), and MM (n = 0/1)). Overall rates of high-risk patients were 84.4% for UCBT recipients and 50.4% for BMT/PBSCT recipients(P<0.05). 11.6 percent of UCB grafts and 100% sibling grafts were HLA-identical (antigen level for HLA-A and B, allelic for DRB1, respectively). All patients received myeloablative conditioning regimens and CsA plus mycophenolate mofetil as GVHD prophylaxis. The median number of nucleated cells and CD34+ cells infused were 0.36 (r 0.19–0.69)×108 and 0.21(r 0.06–0.52)×106 per kilogram of the recipient's body weight for UCBT recipients, and 5.68 (r 2.02–12)×108 and 3.63(r 0.67∼14.99)×106 per kilogram for BMT/PBSCT recipients (P=0.000). The primary engraftment rate was 96.1% (UCBT) and 100% (BMT/PBSCT). The median time to 0.5×109/L ANC was 19 days (r 12–35) and 12 days(r 10–18)(P = 0.000) and the median time to 20×109/L platelets was 36 days(r 14–90)and 15 days(r 11–17)(P = 0.001); hematopoietic recovery was significantly delayed after UCBT. The cumulative incidence of total acute GVHD (47.3% vs.22.2%, P = 0.001), early transplantation-related mortality (TRM) before day +100 (13.0% vs.3.4%, P<0.05), and infection (58.4%vs. 12.0%, P<0.05) was higher in UCBT recipients. Median follow-up was 42.2 months (range, 4.5–123.2 months) for BMT/PBSCT recipients and 22.2 months (range, 3.0–110.2 months) for UCBT recipients. There was no significant difference in cumulative incidence of grades ?to ? acute GVHD (9.4% vs. 5.0% P = 0.247), relapse rate (14.3% vs. 14.5%, P=0.962), and 3 year over survival (OS) (59.6% vs. 64.1%, P=0.123). But the cumulative incidence of chronic GVHD (18.8% vs. 44.1%) and extensive chronic GVHD (0% vs. 18%) was lower in UCBT recipients (P<0.05). The estimated 9-M CI of discontinuing immunosuppressive therapy (IST) while alive was 80%, and long-term survivors of UCBT had better quality of life. Our data shows similar survival, but better quality of life after myeloablative transplantation using UCB versus identical sibling hematopoietic cells in adults with hematologic malignancies. HLA-mismatched cord blood should be considered an acceptable source of hematopoietic stem-cell grafts for adults in the absence of an HLA-matched adult donor. Disclosures: Sun: Anhui Provincial “115” Industrial Innovation Program (2009): Research Funding; the Fund of the Key Medical Project of Anhui Provincial Healthy Department (2010A005): Research Funding; Key Scientific and Technological Project of Anhui province “Twelfth Five-Year Plan” (11010402164): Research Funding.

scholarly journals Incidence of Invasive Fungal Infections (IFI) in Pediatric Acute Lymphoblastic Leukemia (ALL) and the Impact of Antifungal Prophylaxis in an Endemic Area

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1215-1215
Author(s):  
Simone M Chang ◽  
Mason Holt ◽  
Lauren Hernandez ◽  
Natalie Slone ◽  
Jun Zhao ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Cumulative Incidence ◽  
Endemic Area ◽  
Fungal Infections ◽  
Lymphoblastic Leukemia ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
European Organization ◽  
The Impact

Abstract Background In pediatric hematologic malignancy, the incidence of invasive fungal infections (IFI) is ~ 5-10% and leads to significant morbidity and mortality. Acute lymphoblastic leukemia (ALL) accounts for the largest group at risk and has the largest absolute number of IFI. Antifungal prophylaxis has the potential to mitigate risk of invasive infections in ALL but is not currently standard of care due to the paucity of data in ALL subgroups. A recent systematic review showed a significant reduction in proven/probable IFI and fungal infection-related mortality in pediatric patients when using a mold active agent compared with fluconazole, therefore an echinocandin was selected for systemic antifungal prophylaxis in our institution. In this study we investigate the incidence of IFI in patients with ALL in a highly endemic area (Ohio River Valley) and describe the impact of echinocandin prophylaxis in this population. Methods We conducted a retrospective cohort study of consecutive patients &lt;25 years with ALL from 2015 to 2021 at Norton Children's Hospital, Louisville, KY. IFI was classified as possible, probable, or proven as defined by the 2020 European Organization for Research and Treatment of Cancer/ Mycoses Study Group Consensus Group. Patients were then analyzed in 2 subgroups based on prophylaxis with caspofungin. Inpatient administration of caspofungin was given to patients with high-risk B-ALL (HR B-ALL) and T-ALL as outlined in Table 1. Patient and IFI characteristics were collected, and cumulative incidence analyses used for subgroup comparisons. Results Demographics and patient characteristics are summarized in Table 2. Between 2015 to 2020 we identified 100 patients with ALL. Mean age at diagnosis was 7.2 years and 43% were female. We identified 14 unique cases of IFI in 13 patients with ALL who did not receive prophylaxis with caspofungin during 2015 to 2020 (14%). Prior to the implementation of prophylaxis, IFI occurred in 0% (0/43) of the SR B-ALL group, 18.2% (6/33) in HR B-ALL group and 35% (8/23) in T-ALL group. IFI incidence was highest in induction and consolidation phases (71.4%) and implicated species during these phases included Aspergillus, Candida, Fusarium, and Papulasopora. From April 2020 to July 2021, there were 22 newly diagnosed patients with ALL, 11 (50%) of whom received inpatient prophylaxis with caspofungin. There was 1 case (4.5%) of reported IFI during delayed intensification (no prophylaxis at the time of infection). As seen in Figure 1, patients with HR B-ALL and T-ALL who were hospitalized and received caspofungin during induction saw a notable decrease in the cumulative incidence of IFI, from 18.3% to 0% at 6 months into treatment before reaching similar levels in the patients who did not receive prophylaxis. Conclusion In our pediatric population, patients with T-ALL and HR B-ALL were more likely to develop IFI than those with SR B-ALL. Prophylaxis with caspofungin and inpatient hospitalization during induction were effective strategies for reducing the incidence of IFI in induction and consolidation for our high-risk leukemia population. This approach should be validated in larger studies with special consideration being given to patients in fungal endemic areas. Figure 1 Figure 1. Disclosures Raj: Terumo Medical Corporation: Honoraria, Speakers Bureau; Forma therapeutics: Consultancy; Global biotherapeutics: Speakers Bureau.

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