Unrelated Cord Blood Transplantation and Post-Transplant Cyclophosphamide (PT-CY)

Background .There has been a decrease in the use of unrelated cord blood transplants (UCBT) in the past years: this is probably due to slow hematologic and immune recovery, resulting in a relatively high non relapse mortality (NRM). The addition of anti-thymocyte globulin (ATG) in the conditioning prevents graft versus host disease (GvHD) but makes immune recovery very slow. In addition there is a growing competition of unmanipulated haploidentical transplants. Aim of the study. We have opened a pilot study to test whether high dose post-transplant cyclophosphamide (PT-CY) would prevent GvHD but still allow for robust immune and hematologic recovery . Methods. We have grafted 10 patients with an unrelated CB unit and PT-CY. The conditioning regimen was thiotepa (10 mg/kg), busulfan 9.6 mg/kg and fludarabine 150 mg/m^2 (TBF). GvHD prophylaxis was cyclosporin (CSA) starting day 0 (3 mg/kg/day(i.v.), mycophenolate (MMF) 30 mg/kg starting day +1 (p.o) , and PT-CY 30 mg/kg days +3 and +5. The median patients' age was 58 (43-66), and the median weight was 75 kg (54-85) the diagnosis was AML in 8 patients, Ph'+ALL in one and RAEB in one patient; 6 patients were in remission and 4 had active disease. CB units. The HLA matching of the CB unit was 5/8 antigens/alleles (A,B,C,DRB1) in six patients, 4/8 in two and 2/8 in one. The median nucleated cell dose was 3.1x10^7/kg (range 1.8- 4.5). The ABO was mismatched in all 10 patients. Hematologic recovery: median time to neutrophils 0.5x10^9/l was day 23 days (range 17-27) and the median time to a platelet count of 20x10^9/L was 38 days (range 34-40). The median counts on day +50 were as follows: Hb 9,1 gr/dL (range 8.7-11.1), Neutrophils 2,3 x10e9/L (range 1-5), PLTs 56 x10e9/L (10-90). One patient failed to engraft and received a second transplant from an unrelated donor, which was successful. No patient developed pure red cell aplasia despite 9/10 being ABO major mismatched. CD4 recovery : the median CD4 count on day +50 was 74 /cmm (range 67-116) and on day +100 it was 111/cmm(range 100-136). CMV pre-emptive therapy occurred in 3/6 evaluable patients Outcome: two patients with advanced disease, died early of infections, within day +20. GvHD was seen in 1 patient as a transient rash. No patient was treated for GvHD. No patient developed chronic GvHD. No patient relapsed. Eight patients survive in remission, with a median follow up of 6 months, and a projected one year actuarial survival of 80%. Readmissions were extremely rare. Conclusions. These first 10 patients suggest that UCBT followed by PT-CY, CSA, MMF, as GvHD prophylaxis is feasible and leads to encouraging hematologic and immunologic recovery. We were particularly impressed with the lack of GvHD, the absence of relapses and the good quality of life. Figure Disclosures No relevant conflicts of interest to declare.

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Unrelated cord blood transplantation for adult patients with advanced myelodysplastic syndrome

Blood ◽

10.1182/blood-2002-12-3917 ◽

2003 ◽

Vol 101 (12) ◽

pp. 4711-4713 ◽

Cited By ~ 64

Author(s):

Jun Ooi ◽

Tohru Iseki ◽

Satoshi Takahashi ◽

Akira Tomonari ◽

Koji Ishii ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Cord Blood ◽

Median Time ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Adult Patients ◽

Unrelated Cord Blood Transplantation ◽

Blood Transplantation ◽

Unrelated Cord Blood

AbstractWe report the results of unrelated cord blood transplantation (CBT) for 13 adult patients with advanced myelodysplastic syndrome (MDS). The median age was 40 years, the median weight was 51 kg, and the median number of infused nucleated cells was 2.43 × 107/kg. Twelve patients had myeloid reconstitution, and the median time to more than 0.5 × 109/L (5 × 108/L) absolute neutrophil count was 22.5 days. A self-sustained platelet count more than 50 × 109/L was achieved in 11 patients at a median time of 49 days. Acute graft versus host disease (GVHD) occurred in 9 of 12 evaluable patients and chronic GVHD in 8 of 11 evaluable patients. Ten patients are alive and free of disease at between 171 and 1558 days after transplantation. The probability of disease-free survival at 2 years was 76.2%. These results suggest that adult advanced MDS patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.

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Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies

Frontiers in Immunology ◽

10.3389/fimmu.2021.733326 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hua Li ◽

Xiaofan Li ◽

Yiling Chen ◽

Duihong Li ◽

Xianling Chen ◽

...

Keyword(s):

Cord Blood ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Hematologic Malignancies ◽

Post Transplantation ◽

Blood Transplantation ◽

Gvhd Prophylaxis ◽

Unrelated Donors ◽

Unrelated Cord Blood

Allogeneic haploidentical HSCT (haplo-HSCT) and unrelated umbilical cord blood transplantation(UCBT)are used in patients lacking HLA-identical sibling or unrelated donors. With myeloablative condition and GVHD prophylaxis of using low-dose ATG and post-transplantation cyclophosphamide (PTCY), we conducted a prospective clinical trial. Of eligible 122 patients from February 2015 to December 2019 in the study, 113 patients were involved. Forty-eight patients were in the group of sequential haplo-cord transplantation (haplo-cord HSCT), and 65 patients were in the group of single UCBT. The primary endpoint of 2-year disease-free survival (DFS) was no statistical difference between groups (64.1 vs. 56.5%), p>0.05. The analysis of subgroup patients with relapsed/refractory showed haplo-cord HSCT was associated with better OS (HR 0.348, 95% CI, 0.175–0.691; p=0.0025), DFS (HR 0.402, 95% CI, 0.208–0.779; p=0.0069), and GRFS (HR 0.235, 95% CI, 0.120–0.457, p<0.0001) compared to the single cord group. The 2-year’s probability in OS, DFS, and GRFS was 64.9 vs. 31.6%, 64.5 vs. 31.6%, and 60.8 vs. 15.0% in the haplo-cord group and single cord group, respectively. III-IV acute GVHD 8.3 vs. 6.2%, chronic GVHD 25.8 vs. 13.7%, and extensive chronic GVHD 5.3 vs. 1.8% were shown in corresponding group, p>0.05. The patients engrafted persistently with UCB showed better survival outcomes. Our sequential Haplo-cord HSCT with ATG/PTCY improved the survival of patients and might be an alternative transplantation approach for patients with relapsed/refractory hematologic malignancies.

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Preliminary Results of Combined Haploidentical-Cord Blood Transplantation for Patients Lacking HLA Identical Donors

Blood ◽

10.1182/blood.v112.11.3015.3015 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3015-3015 ◽

Cited By ~ 1

Author(s):

Elizabeth Shima Rich ◽

Andrew Artz ◽

Theodore Karrison ◽

Amittha Wickrema ◽

Loren Joseph ◽

...

Keyword(s):

Cord Blood ◽

Median Time ◽

Interstitial Pneumonitis ◽

Bone Marrow Cells ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Blood Transplantation ◽

Gvhd Prophylaxis ◽

Total Body

Abstract Background: Many patients (pts), particularly minorities, lack matched unrelated donors. Mismatched cord blood (CB) transplantation causes less graft versus host disease (GVHD), but is associated with delayed hematopoietic recovery. We studied an alternative donor regimen using T-cell depleted haploidentical stem cells and unrelated CB pioneered by Magro et al. (Haematologica2006;91:640–8) to confirm engraftment with acceptable rates of GVHD. Patients and Methods: We enrolled 15 pts (7 AML, 1 ALL, 2 MDS, 1 CML, 3 NHL, 1 severe aplastic anemia) lacking HLA identical donors. The median age was 28 years (range, 4–66) and median weight was 75 kg (range, 14–124). Twelve pts had active disease at transplant; 2 had prior autologous transplants. Eight pts were Caucasian; 7 other race or ethnicity. The haploidentical donor was the mother in 3; father in 1; child in 4; sibling in 5; and half-sibling in 2 cases. The median haploidentical CD34+ dose was 2.41 × 106/kg (range, 1.25–6.26); CD3+ cells were 0.8 × 104/kg (range, 0.3–1.3). Single unrelated CB units were matched by low resolution at HLA-A and B and high-resolution at DRB1, and matched 6/6 in 1 pt; 5/6 in 7 pts; 4/6 in 6 pts; 3/6 in 1 pt. Median cord total nucleated cells equaled 2.39 × 107/kg (range, 1.07–9.36); CD34+ cells were 0.14 × 106/kg (range, 0.04–0.75). The conditioning regimen for most pts was fludarabine (Flu) (30 mg/m2 × 5 days), thiotepa (5 mg/kg × 2 days), total-body irradiation (TBI) (12 Gy lateral opposed fields), and Thymoglobulin® (rATG) (1.5 mg/kg × 4 days). Five pts unable to tolerate TBI received Flu, melphalan (70 mg/m2 × 2 days), and rATG. GVHD prophylaxis consisted of tacrolimus (Tac) + methylprednisolone or Tac + mycophenolate. Results: Two pts died early (sepsis, CVA). Twelve of the remaining 13 pts engrafted. One pt failed to engraft and died on day (d)36. Median time to ANC >500/mL was 9 days (range, 9–12). Median time to sustained platelets >20,000/mL was 24 days (range, 12–63). Early haploidentical engraftment was replaced by durable engraftment of CB by 100 days. In unfractionated peripheral blood or bone marrow cells, median haploidentical chimerism was 95% (range, 0–100) on d14; 76% (range, 0–93) on d30; 36% (range, 0–83) on d55; 0% (range, 0–42) on d100; and 0% on d180. Median unfractionated cord chimerism was <5% (range, 0–100) on d14; 24% (range, 7–100) on d30; 64% (range, 17–100) on d55; 100% (range, 58–100) on d100; and 100% on d180. In the CD3+ compartment, median haploidentical chimerism was 94% (range, 0–100) on d14; 72% (range, 0–93) on d30; 24% (range, 0–76) on d55; 0% (range, 0–39) on d100; and 0% on d180. Median CD3+ cord chimerism was 6% (range, 0–100) on d14; 28% cord (range, 7–100) on d30; 76% (range, 24–100) on d55; 100% (range, 61–100) on d100; and 100% (range, 90–100) on d180. Four pts died of sepsis. One pt died of VOD; 2 pts who also received TBI developed interstitial pneumonitis, 1 fatal. Two pts relapsed and died. Cumulative d100 treatment-related mortality (TRM) was 44% (95% CI: 22 to 73%). Acute skin GVHD grade I–II occurred in 3 pts. No cases of chronic GVHD developed. Five pts are currently alive and in remission with complete CB chimerism. The median follow up for survivors is 207 days (range, 23–283). The median age of survivors is 27 years (range, 20–67). Conclusions: Combined haploidentical and CB transplantation is a promising strategy for those lacking HLA identical donors - even in the presence of low CB doses - leading to early haploidentical engraftment followed by durable CB predominance by d100. Acute and chronic GVHD are manageable. Complications such as interstitial pneumonitis may be related to the TBI-containing regimen. This donor combination, with further modifications to decrease TRM, warrants further study in pts lacking HLA identical donors.

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Unrelated Cord Blood Transplantation (UCBT) in Children with Sickle Cell Disease (SCD): US Centers Experience.

Blood ◽

10.1182/blood.v106.11.2044.2044 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2044-2044 ◽

Cited By ~ 2

Author(s):

Tom V. Adamkiewicz ◽

Ann Haight ◽

Melissa A. Mazur ◽

K. Scott Baker ◽

Paul Szabolcs ◽

...

Keyword(s):

High Risk ◽

Cord Blood ◽

Acute Gvhd ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Post Transplant ◽

Elevated Liver Enzymes ◽

Unrelated Cord Blood ◽

Reduced Intensity ◽

Grade Iii

Abstract UCBT may be curative in patients (pts) with high-risk SCD. Unrelated cord blood units matched at >4/6 HLA are acceptable for UCBTs and available to most pts. We reviewed UCBTs in 7 children with SCD and cerebrovascular accidents performed in 4 centers (1998 to 2003): 4 pts were conditioned with conventional myeloablative regimens, and 3 pts with reduced-intensity regimens. The former received busulfan (BU), cyclophosphamide (CY) and anti-thymocyte globulin (ATG) (3 pts) or BU/CY/ATG plus fludarabine (FLU) (1 pt). Of 3 pts who received 4/6 HLA-matched UCBTs after BU/CY/ATG and GVHD prophylaxis with methylprednisone (MP) and cyclosporine (CSP) or tacrolimus (TAC), 2 have durable engraftment, 1 had autologous reconstitution (BMT2004; 34:405–11). A 5 yr old (yo) female with transfusion-induced alloimmunization received a 5/6 HLA-matched UCBT (6.2 X 10^7/kg nucleated [NC] cells) after BU/CY/ATG/FLU, followed by CSP and MP post-transplant. PMN engraftment and VNTR > 98% of donor origin were documented 24 and 37 days, respectively, after UCBT. Complications included elevated liver enzymes during conditioning, grade IV GVHD of skin, GI and liver, grade III mucositis, VOD, parainfluenza 3 infection, candidemia and adenovirus viremia. Pt died of severe acute GVHD and multi-organ failure 73 days after UCBT. Two different reduced-intensity regimens were used in the other 3 pts. An 8 yo male received a 4/6 HLA-matched UCBT (3.2 X 10^7/kg NC) after conditioning with alemtuzumab, rituximab, hydroxyurea, thiotepa and TBI (600cGy, with 300 cGy total dose to liver and kidneys) and received TAC and mycophenolate mofetil (MMF) post-transplant. This patient failed UCBT 8 months earlier (FLU/CY/ATG/TLI, 4/6 HLA). PMN engraftment and VNTR > 98% of donor origin was documented within 18 days after UCBT. Complications included grade I skin GVHD, grade 1 mucositis and parainfluenza 1 infection. This pt remains engrafted and fully active 1.6 ys after UCBT. A 4 yo female and a 16 yo male received 4/6 or 5/6 HLA-matched cord units, respectively, after BU or CY, ATG, FLU and total lymphoid irradiation (200 or 500 cGy) and received CSP and MMF post-transplant. Neither had evidence of donor engraftment, and autologous reconstitution was documented within 2 weeks after UCBT. Sustained donor engraftment occurred in 3/4 pts (75%) who underwent UCBT after myeloablative conditioning and 1/3 pts (33%) who underwent UCBT after reduced-intensity conditioning. Two of the 3 pts who engrafted after myeloablative preparative regimens developed acute grade III–IV GVHD, and 1 of these pts developed extensive chronic GVHD. The 1 pt who engrafted after a reduced-intensity preparative regimen developed grade I acute GVHD only. Significant viral infections (CMV 1 pt, adenovirus, parainfluenzavirus 2 pts each) occurred in 4 pts. In this limited experience, following various conditioning regimens, optimal GVHD and infection prevention remains a challenge. Both apparent lesser risk and documented durable engraftment may justify further development of non-myeloablative strategies for UCBT in children with high-risk SCD.

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Unrelated Cord Blood Transplants in Children with Acute Leukemia: Experience of a Single Center

Blood ◽

10.1182/blood.v112.11.4424.4424 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4424-4424

Author(s):

Rosa Branca Ferreira ◽

Carlos Pinho Vaz ◽

Isabel Barbosa ◽

Susana Roncon ◽

Fernando Campilho ◽

...

Keyword(s):

Cord Blood ◽

Lymphoblastic Leukemia ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Unrelated Donor ◽

Gvhd Prophylaxis ◽

Successful Transplantation ◽

Unrelated Donors ◽

Alternative Sources ◽

Unrelated Cord Blood

Abstract Allogeneic stem cell transplantation is an accepted treatment modality for selected malignant diseases. However, the ability to identify suitable related or unrelated donors can be difficult in some patients (pts). Alternative sources of stem cells such as cord blood (UCB) provide a readily available graft mainly for pediatric patients. Between October 1996 and May 2008, 23 consecutive patients (pts), with a median age of 6 years old (range:1 – 11), 13 male and 10 female, underwent UCB transplant for the treatment of acute lymphoblastic leukemia (n= 15), acute myeloid leukemia (n=7) and acute byphenotypic leukemia (n= 1). Conditioning regimen consisted of intravenous busulfan (3.2 mg/kg/day x 4 days), cyclophosphamide (120 mg/Kg) and rabbit antithymocyte globuline (15 mg/Kg) ±melphalan (140 mg/m2) and GVHD prophylaxis consisted of a calcineurin inhibitor and MMF or MTX. All grafts were HLA mismatched. The median infused cell doses were, respectively 3.2× 107/kg (range: 1.2–21) and 1.27×105/kg (range:0.2–4.3) for nucleated cells (NC) and CD34 + cells. Engraftment occurred in 18 pts (75%). Five pts failed engraftment, of wich 4 underwent a second transplant (3 autologous and 1 haploidentical) and 1 died of infection at day +59. Grade II–IV acute GVHD occurred in 12 pt and chronic GVHD in 2 of 14 pt at risk. With a median follow up of 1,5 years (range: 3 months-9.5 years), overall survival (OS) at 3 years is 40% (± 13%) and event free survival (EFS) at 3 years is 32% (± 11%). Non relapse mortality (NRM) was 13.6 % (± 7.3%). UCB transplants represents a valuable alternative to bone marrow or peripheral blood especially for pts requiring urgent transplant or lacking an HLA matched unrelated donor and having the potential advantage of an immune tolerance allowing successful transplantation despite HLA disparity

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Donor Lymphocyte Infusions (DLI) Following Haplo Bone Marrow Transplantation (hBMT) with High-Dose of Cyclophosphamide Post-Transplant As Gvhd Prophylaxis

Blood ◽

10.1182/blood.v120.21.1950.1950 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1950-1950

Author(s):

Anna Ghiso ◽

Annamaria Raiola ◽

Francesca Gualandi ◽

Alida Dominietto ◽

Riccardo Varaldo ◽

...

Keyword(s):

T Cell ◽

Median Time ◽

Myeloid Leukemia ◽

Chronic Gvhd ◽

High Dose ◽

Cell Leukemia ◽

Myeloablative Conditioning ◽

Post Transplant ◽

Gvhd Prophylaxis ◽

Donor Lymphocyte Infusions

Abstract Abstract 1950 Background: In the haploidentical setting, the use of donor lymphocyte infusions (DLI) is associated with a significant risk of acute and chronic graft vs host disease (GvHD): in one report, a median T-cell dose of 2.4 × 10⋀8/kg was administered to recipients of unmanipulated haploidentical stem cell transplants, and a cumulative incidence of chronic GVHD of 50% was reported (Huang X, BBMT 2009). It is possible that patients receiving high dose Cyclophosphamide post-transplant (PT-CY) may be able to receive DLI with a lower risk of GvHD Aim of the study: We tested the feasibility and occurrence of GVHD, following 32 DLI administered in sixteen patients, who relapsed after an unmanipulated haploidentical T-cell replete BMT, and PT-CY. Patients and Methods: All sixteen patients were transplanted from haploidentical related donor, after a myeloablative conditioning (n=10) or a non myeloablative conditioning (n=6) with PT-CY as GVHD prophylaxis, in association with CyA and micophenolate. The diagnosis was Hodgkin's lymphoma (n 6), acute lymphoblastic B-cell leukemia (n=3), acute myeloid leukemia (n=5), pro-lymphocytic T-cell leukemia (n=1), chronic myeloid leukemia blast crisis (n=1). The median time of relapse was 211 days from transplant (range 45–697 days); the median time at DLI was 48 days from relapse (range 29–540 days) and 252 days from transplant (range 109–690). Ten patients had hematologic relapse, while six had molecular relapse. At time of first DLI all patients were off GVHD prophylaxis. The minimum dose of lymphocytes was 1 × 103̂/kg (n=2); higher doses were as follows: 1 × 104̂/kg (n=13), 1 × 105̂/kg (n=11), 5 × 105̂/kg (n=4), 1 × 106̂/kg (n=2). The median number of DLI/patient, was 1 (range 1–5). In eleven cases DLI followed chemotherapy: gemcitabine or bendamustine in Hodgkin's lymphoma and pro-lymphocytic leukemia; fludarabine, ara-C and antracycline containing regimens in acute leukemia. Median time of DLI was 12 days from chemotherapy (range 10–14 days), during the chemotherapy-induced nadir. Five patients received DLI alone. Results: The infusions were well tolerated and no major adverse effect was observed. The cumulative incidence of acute GvHD grade II-III, was 6%, and 0% for chronic GVHD. No aplasia related to haplo-DLI occurred. Five patients died with progressive disease; 11 patients are surviving (69%), 4 of them are disease-free, seven have active disease; two patients relapsed after 313 and 135 days from DLI, respectively. The median follow-up is 221 days (range 46–559 days). Conclusions: This study suggests that patients grafted with haplo-mismatched BMT and high dose post-transplant cyclophosphamide, can be treated with DLI at doses up to 1× 106̂/kg, with a very low risk of developing acute or chronic GVHD. Disclosures: No relevant conflicts of interest to declare.

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Improved Outcome of Unrelated Cord Blood Transplantation in Children with Severe Aplastic Anemia

Blood ◽

10.1182/blood.v128.22.3503.3503 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3503-3503

Author(s):

Kazuko Kudo ◽

Hideki Muramatsu ◽

Nao Yoshida ◽

Ryoji Kobayashi ◽

Hiromasa Yabe ◽

...

Keyword(s):

Cord Blood ◽

Aplastic Anemia ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Cell Number ◽

Secondary Malignancy ◽

Blood Transplantation ◽

Gvhd Prophylaxis ◽

Conditioning Regimens ◽

Unrelated Cord Blood

Abstract Introduction Hematopoietic stem cell transplantation (HSCT) from an HLA-matched related donor is a first-line treatment for children with severe aplastic anemia (SAA). HSCT from an HLA-matched unrelated donor (MUD) is indicated as a salvage treatment for non-responders to immunosuppressive therapy (IST).Because unrelated cord blood transplantation (UCBT) has been considered as an experimental therapy, information of UCBT in patients with SAA is scarce, especially in pediatric patients. We analyzed the outcomes of UCBT in children with AA registered in the Transplant Registry Unified Management Program (TRUMP) conducted by the Japanese Society for Hematopoietic Cell Transplantation. Patients and Methods Between 1998 and 2013, 27 patients <15 years old who underwent an UCBT as the first HSCT were registered in the TRUMP database. Patients with congenital bone marrow failure syndrome such as Fanconi anemia were excluded from the analysis. Treatment failure were defined as death by all causes, graft failure (GF) and secondary malignancy. Data collected as October 2014 were analyzed. Results Patients' characteristics Among the 27 patients, 10 patients underwent UCBT during 1998 - 2005 and 17 patients underwent UCBT during 2006 - 2013. The median age at the time of UCBT was 6 years (range, 0 - 14). The male/female ratio was 12/15. The median interval between the diagnosis of AA and CBT was 212 days (range, 39 - 2,982). Sixteen patients received antithymocyte globulin (ATG) as immunosuppressive therapy (IST) before UCBT. The median total nucleated cell number and CD34 positive cell number at cryopreservation were 3.99 x 107/kg (range, 0.09 - 16.11 x 107/kg) and 1.31 x 105/kg (range, 0.39 - 6.17 x 105/kg), respectively. Ten patients received fludarabine (FLU) + cyclophosphamide (CY) + irradiation ± ATG. Six received FLU + CY + ATG. Four received FLU + melphalan (MEL) + irradiation and the remaining 7 received other various conditioning regimens. Cyclosporine was used in 9 patients and tacrolimus was used in 17 patients for graft-versus-host disease (GVHD) prophylaxis. Transplantation outcomes Neutrophil recovery was observed in 19 patients and the median time to engraftment was 20 days. Platelets engraftment was observed in 17 patients and the median time to engraftment was 50 days. One patient experienced secondary GF. Sustained engraftment was observed in 18 patients. Grade II - IV acute GVHD, limited chronic GVHD, and extensive chronic GVHD were observed in 6 (26%), 2 (10%), and 2 patients (10%), respectively. With median follow-up times of 18 months after CBT, 19 of 27 patients were alive. Causes of death included bacterial/fungus infections in 3, veno-occulusive disease (VOD) in 2, EBV-LPD, hematologic malignancy, and secondary GF in each 1 patient. The 5-year overall and failure-free survival (OS, FFS) of all patients were 69.5±9.0% and 59.3±9.5%, respectively. The 5-year OS and FFS of 17 patients who underwent UCBT after 2006 was 93.8±6.1% and 76.0±10.5%, respectively. Primary GF was observed in 8 patients, including 3 who underwent UCBT during 2006 - 2013. Two patients, who underwent UCBT after 2006, received FLU + CY + ATG without irradiation and remaining one patient received CY + ATG + total body irradiation (TBI). We screened anti-HLA antibodies in 8 patients but none of them were positive. The conditioning regimens including ATG exhibited a significantly worse FFS than those without ATG (33.3±12.2 % vs 91.7±8.0 %, P=0.004). On the other hand, the conditioning regimens including irradiation exhibited a better FFS than those without irradiation (75.0±9.7 % vs 14.3±13.2 % , P=0.01). The 5 year FFS of FLU + MEL + irradiation regimen (n=4) and FLU + CY + irradiation regimen (n=10) was 100% and 90%±9.5%, respectively. Univariate analysis resulted in no statistical significant differences in OS and FFS in HLA disparities, total nucleated cell number and CD34 positive cell number at cryopreservation, and methods of GVHD prophylaxis. One patient developed secondary malignancy. Discussion Our study showed that a reduced conditioning regimen with Flu, MEL/CY and low-dose irradiation may be an optimal regimen for SAA children receiving UCBT. An important finding is that ATG has no benefit in this setting. A prospective study with larger number of patients is warranted to confirm our promising results. Disclosures Kojima: SANOFI: Honoraria, Research Funding.

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Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies

Blood ◽

10.1182/blood.v98.8.2332 ◽

2001 ◽

Vol 98 (8) ◽

pp. 2332-2338 ◽

Cited By ~ 189

Author(s):

Guillermo F. Sanz ◽

Silvana Saavedra ◽

Dolores Planelles ◽

Leonor Senent ◽

Jose Cervera ◽

...

Keyword(s):

Cord Blood ◽

Median Time ◽

Antithymocyte Globulin ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Disease Free Survival ◽

Hematologic Malignancies ◽

Unrelated Donor ◽

Blood Transplantation ◽

Disease Free

Abstract The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 × 107/kg (range, 1.01 × 107/kg to 4.96 × 107/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 × 109/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 × 109/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P = .01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.

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Haploidentical Stem Cell Transplantation (HAPLO-HSCT) With High Dose Cyclophosphamide Post-Transplant (HD-CY) As Gvhd Prophylaxis In High Risk Hematologic Malignancies: Multicentric Spanish Experience

Blood ◽

10.1182/blood.v122.21.2173.2173 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2173-2173

Author(s):

Jorge Gayoso ◽

Pascual Balsalobre ◽

Mi Kwon ◽

María Jesús Pascual ◽

Cristina Castilla-Llorente ◽

...

Keyword(s):

High Risk ◽

Immune Reconstitution ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Hematologic Malignancies ◽

High Dose ◽

Unrelated Donor ◽

Post Transplant ◽

Gvhd Prophylaxis ◽

Grade Ii

Abstract Introduction Allogeneic transplantation is the only curative option for patients with high risk hematologic malignancies. Only one third of them have an HLA identical sibling donor and around 60-70% will find an unrelated donor, that´s why HAPLO-HSCT offers a therapeutic option to most of these patients with the advantages of quick availability, easy programation and logistics, and a committed donor. Patients and methods We retrospectively evaluate the results of HAPLO-HSCT with reduced conditioning or myeloablative regimens and GVHD prophylaxis based on HD-CY (50 mg/kg on days +3 and +4) and a calcineurin inhibitor plus mycophenolate from day +5 performed in GETH centers. Results From Dec-2007, 80 HAPLO-HSCT have been done in 14 centers. Median age was 37 years (16-66), 67.5% were males and all were in advanced phases of their disease or presented high risk features (29 Hodgkin´s, 22 AML, 9 ALL, 8 MDS, 5 NHL, 4 myeloma and 2 myelofibrosis). Previous HSCT has been employed in 65%, autologous in 38 and allogeneic in 15 (5 siblings, 3 unrelated and 7 cord blood transplants), and in 35% the HAPLO-HSCT was their first transplant. Disease status at HAPLO-HSCT was CR in 45%, with persistent disease in 55%. Bone marrow was the graft source for 51% and peripheral blood for 49%, non T-cell depleted in all cases. The haploidentical donor was the patient´s mother (21), father (7), brother/sister (35) or offspring (17). Non-myeloablative conditioning was employed in 77.5% and myeloblative in 22.5%. Median neutrophils engraftment was reached at day +18 (13-45) and platelets >50K at day +27 (11-150). Main toxic complications were grade II-III muchositis in 36%, febrile neutropenia in 75% and CMV reactivations in 62%, with a transplant related mortality rate of 12.5% at day +100 and 19% at 6 months post-transplant. Acute GVHD grade II-IV affected to 24/73 patients at risk (33%), with grade III-IV in 10/73 (14%). Chronic GVHD was present in 12/51 (24%), being extensive in 6/51 (12%). After a median follow-up of 9 months (0.3-49), 26/80 patiens have died due to relapse in 13, infections in 10 and GVHD in 3 cases. Event-free survival and overall survival at 1 year were 48% and 60% respectively. Immune reconstitution was fast and complete in those evaluated. Conclusions HAPLO-HSCT with HD-CY is a useful tool in the treatment of high risk hematologic malignancies, rendering long-lasting remissions with limited toxicity, low GVHD incidence and early immune reconstitution. Disclosures: No relevant conflicts of interest to declare.

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Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia

Blood ◽

10.1182/blood-2003-07-2420 ◽

2004 ◽

Vol 103 (2) ◽

pp. 489-491 ◽

Cited By ~ 83

Author(s):

Jun Ooi ◽

Tohru Iseki ◽

Satoshi Takahashi ◽

Akira Tomonari ◽

Kashiya Takasugi ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Cord Blood ◽

Median Time ◽

Myeloid Leukemia ◽

De Novo ◽

Cord Blood Transplantation ◽

Adult Patients ◽

Blood Transplantation ◽

Unrelated Cord Blood ◽

Acute Myeloid

Abstract We report the results of unrelated cord blood transplantation (CBT) for 18 adult patients with de novo acute myeloid leukemia (AML). The median age was 43 years, the median weight was 55.2 kg, and the median number of cryopreserved nucleated cells was 2.51 × 107/kg. Seventeen patients had myeloid reconstitution and the median time to more than 0.5 × 109/L absolute neutrophil count was 23 days. A self-sustained platelet count more than 50 × 109/L was achieved in 16 patients at a median time of 49 days. Acute graft-versus-host disease (GVHD) above grade II occurred in 11 of 17 evaluable patients and chronic GVHD occurred in 14 of 17 evaluable patients. Fourteen patients are alive and free of disease at between 185 and 1332 days after transplantation. The probability of disease-free survival at 2 years was 76.6%. These results suggest that adult AML patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.

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