scholarly journals An ATG free conditioning regimen using Fludarabine and Cyclophosphamide is associated with good outcomes in patients undergoing matched related family donor transplants for aplastic anaemia: ATG free fludarabine based conditioning in aplastic anaemia

2021 ◽  
Author(s):  
Biju George ◽  
Sharon Lionel ◽  
Sushil Selvarajan ◽  
Fouzia N Abubacker ◽  
Anu Korula ◽  
...  
Keyword(s):  
Aplastic Anaemia ◽  
Conditioning Regimen ◽  
Related Family ◽  
Family Donor

scholarly journals Role of Allogeneic Hematopoietic Stem Cell Transplantation in t(4;11) Positive Acute Lymphoblastic Leukemia (ALL): A Retrospective Multicenter Study of the Italian Association of Pediatric Hematology and Oncology (AIEOP)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1243-1243
Author(s):  
Luca Lo Nigro ◽  
Marco Zecca ◽  
Franca Fagioli ◽  
Edoardo Lanino ◽  
Chiara Messina ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Advanced Disease ◽  
Conditioning Regimen ◽  
Age At Diagnosis ◽  
Hematopoietic Stem ◽  
Donor Type ◽  
Family Donor

Abstract Background. Disease-free survival (DFS) for children with ALL exceeds 80%. Nevertheless, the cure rate can be significantly lower in patients with specific chromosomal translocations, confering poor prognosis. The t(4;11) translocation can be detected in 1-3% of children with ALL and is associated with aggressive clinical course and high risk of treatment failure and relapse. Consequently, patients with t(4;11) may be offered allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR), although the role of HSCT in this setting is still unclear. Patients and Methods. Data on children with t(4;11) positive ALL treated with allogeneic HSCT in AIEOP Centers from 1990 to 2013 were retrospectively collected, and the impact of patient- and treatment-related variables on the clinical outcome was evaluated. A total of 72 consecutive children with t(4;11) positive ALL were analyzed; 33 patients were males and 39 female. The median age at diagnosis was 11 months (range, 1.2 months - 15 years). 38 patients (53%) had an age at diagnosis < 12 months (defined as infants) and 22 were younger than 6 months at diagnosis. The median WBC count was 167x109/l. The majority of infants (30 patients) were enrolled into Interfant 99 and 06 protocols, while the 34 children older than 12 months of age were enrolled into AIEOP 95, 2000, R-2006 and 2009 protocols, respectively. 46 children (64%) were transplanted in first CR, 18 (25%) in second CR and the remaining 8 (11%) in a more advanced disease phase. 35 patients received HSCT from a matched unrelated donor (MUD), 28 from a matched family donor (MFD) and 9 from a partially matched family donor (PMFD). TBI was used in 40% of patients, while a busulfan-based conditioning regimen was used in 56% of cases. Results. 5-year overall survival (OS) and DFS were 54% (42-67) and 47% (35-60), respectively. Transplant-related mortality (TRM) and relapse incidence (RI) were 20% (13-33) and 32% (23-46), respectively. DFS by donor type was as follow: MFD 51%, MUD 52% and PMFD 22%, respectively (P = 0.04). TRM by donor type was 20% for MFD, 14% for MUD and 44% for PMFD, respectively (P = 0.03). DFS was 60% for children transplanted in 1st CR, 30% for patients transplanted in 2nd CR and 25% for those with more advanced disease (P = 0.002). DFS was 40% for children with an age at diagnosis < 6 months, 46% for those with an age at diagnosis between 6 and 12 months, 40% for the 12-24 months group and 57% for patients with an age at diagnosis > 24 months (P = N.S.). DFS was 61% for children receiving TBI and 39% for those treated with a chemo-based conditioning (P = 0.089). Conclusions. Our analysis suggests that HSCT in first remission is a valid therapeutic option for children with t(4;11) positive ALL. Patients transplanted in 1st CR, as well as those receiving a TBI-based conditioning regimen, had a better outcome. MFD and MUD transplants were associated with a similar DFS probability. Disclosures No relevant conflicts of interest to declare.

scholarly journals Sirolimus-Based Immunosuppression as GvHD Prophylaxis after Bone Marrow Transplantation for Severe Aplastic Anaemia: A Case Report and Review of the Literature

2015 ◽  
Vol 2015 ◽  
pp. 1-3
Author(s):  
Katia Perruccio ◽  
Elena Mastrodicasa ◽  
Francesco Arcioni ◽  
Ilaria Capolsini ◽  
Carla Cerri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Aplastic Anaemia ◽  
Marrow Transplantation ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
Severe Aplastic Anaemia ◽  
Leukocyte Antigen ◽  
Gvhd Prophylaxis ◽  
Grade Ii

Congenital or acquired severe aplastic anaemia (SAA) is cured by bone marrow transplantation (BMT) from a histocompatible leukocyte antigen- (HLA-) identical sibling. The best conditioning regimen is cyclophosphamide (CTX) with or without antithymocyte globulin (ATG), followed by short-term methotrexate (MTX) and cyclosporine A (CsA) to prevent graft-versus-host disease (GvHD). In our pediatric oncology-hematology unit, a 5-year-old girl with SAA was treated with two BMT from the same HLA-identical sibling donor. Severe CsA-induced adverse events (severe hypertension and PRES) after the first BMT led necessarily to CSA withdrawal. Alternative immunosuppressive treatment for GvHD prevention as tacrolimus and mycophenolate were not tolerated by our patient because toxicity > grade II. For this reason we decided to administrate sirolimus alone as GvHD prophylaxis and to prevent disease relapse after the rescue BMT. Here we report the successful use of sirolimus alone for GvHD prophylaxis after the second transplant in a pediatric BMT setting for SAA.

scholarly journals Stem Cell Transplantation in Advanced Stage Sickle Cell Disease with Haploidentical T-Cell Depleted PBSC Yields Comparable Outcomes to Matched Sibling Donor Bone Marrow: Results of a Pilot Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3455-3455 ◽  
Author(s):  
Juergen Foell ◽  
Johannes Schulte ◽  
Anja Troeger ◽  
Beatrix Pfirstinger ◽  
Daniel Wolff ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Advanced Stage ◽  
Cell Disease ◽  
Matched Sibling ◽  
Family Donor

Abstract Background: Sickle cell disease (SCD) is an inherited disorder with an estimate of 300,000 affected newborns per year worldwide. Despite improvements in preventive measures and conventional therapy, substantial morbidity and mortality, resulting in a reduced life expectancy persist. Allogeneic hematopoietic stem cell transplantation (HSCT) with a matched sibling donor (MSD) is currently the curative standard of care. However, matched donor availability is <20% and unrelated donor (MUD) HSCT is associated with unacceptably high rates of severe graft-versus-host disease (GvHD). A T-cell depleted HSCT from a haploidentical relative (T-haplo-HSCT) expands donor availability while exhibiting low GvHD rates and thus could offer cure to the remaining 80% of SCD patients (pts). Methods: We report the results of 29 pts with advanced stage SCD transplanted with either a T-cell depleted haploidentical regimen (20 pts, median age 13 years, range 3-31 years) or with bone marrow from a matched family donor (MSD, 9 pts, median age 14, range 9-25 years). Indication for HSCT was advanced stage SCD related complications. Pts with a MSD received a bone marrow (BM) graft. Pts requiring an alternative donor were transplanted with an αß/CD19 (n=5) or CD3/CD19 (n=15) depleted graft from a haploidentical family donor. The conditioning regimen for both groups was identical except that antithymoglobulin (ATG-Neovii®) was given upfront on day -10 to -8 in T-haplo-HSCT and on day -3 to -1 in MSD. Chemotherapy consisted of thiotepa 2 x 5 mg/kg, fludarabine 4 x 40 mg/m2 and treosulfan 3 x 14 g/m2, given between days -10 and -2. Post-HSCT immunosuppression consisted of mofetil mycophenolate and tacrolimus or cyclosporine A for a duration >6 months in T-haplo-HSCT and <6 months in MSD, depending on chimerism. The MSD group received a graft containing a median of 2.4 x 108 cells/kg body weight (BW). The T-haplo-SCT group received a peripheral stem cell allograft with a median of 13.1 x 106 CD34+ cells/kg BW. Results: The conditioning regimen was well tolerated in all pts with no high-grade transplant related toxicity. The overall (OS) and disease-free survival (DFS) with a median follow-up of 17 months in 20 advanced stage mostly adolescent and adult T-haplo-HSCT pts and 22 months in 9 MSD HSCT pts was 90% vs. 100%, respectively. Engraftment was achieved in most pts with stable chimerism over 90%, except for 4 pts with a stable MC in the T-haplo SCT group and 1 patient in the MSD group off immunosuppression. All pts presented a complete BM engraftment of red cell precursors. Only one patient in the T-haplo-HSCT group with a mixed chimerism is still under immunosuppression. The post-HSCT bacterial infectious complications were comparable in both groups and the most common observed viral infections were systemic cytomegaly virus (CMV), adenovirus (ADV), polyomavirus (BKV) and Epstein Barr virus (EBV) reactivations which were successfully treated with intravenous antiviral drugs or virus specific T-cells. Two patients in the T-haplo-HSCT group achieved a DFS off immunosuppression but succumbed to post-HSCT complications. One developed a rotavirus gastroenteritis and an uncontrolled CMV pneumonitis. The other a late graft failure and succumbed to a macrophage activation syndrome. None of our pts developed a Glucksberg Grade III-IV acute GvHD and in the T-haplo SCT group 4 pts (20%) and in the MSD group 2 pts (22%) developed a steroid sensitive mild to moderate cGvHD (fasciitis/oral as well as mild cutaneous GvHD). No extensive cGvHD was observed. To our knowledge this is the largest group of advanced stage SCD pts transplanted with either a T-haplo-HSCT or a MSD approach, according to donor availability, with an almost identical regimen in a direct comparative design. These preliminary results demonstrate increasing evidence for the feasibility, safety and efficacy of a T-haplo-HSCT using CD3/CD19 or αβ/CD19 depleted grafts, in order to offer a curative option to the majority of pts with SCD. A prospective, stratified non-inferiority trial is in preparation (EudraCT number 2018-002652-33) in order to confirm these preliminary results in a large prospective cohort. Disclosures Corbacioglu: Gentium: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria.

Long-Term Outcome of Children with Acute Myeloid Leukemia in First Remission Given Allogeneic HSCT from a Matched Family Donor After a Conditioning Regimen Comprising Busulfan, Cyclophosphamide and Melphalan.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2288-2288
Author(s):  
Marco Zecca ◽  
Riccardo Masetti ◽  
Adriana Balduzzi ◽  
Franca Fagioli ◽  
Giorgio Dini ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
De Novo ◽  
Alkylating Agents ◽  
Conditioning Regimen ◽  
Allogeneic Hsct ◽  
First Remission ◽  
De Novo Aml ◽  
Family Donor

Abstract Abstract 2288 Poster Board II-265 Background. More than 80% of children with de novo acute myeloid leukemia (AML) achieve complete remission (CR) after aggressive induction chemotherapy. However, post-remission treatment plays a crucial role in the final outcome of these patients. In this regards, possible post-remission treatments include high dose chemotherapy, as well as autologous or allogeneic hematopoietic stem cell transplantation (HSCT). In the last years, several groups have compared allogeneic HSCT with chemotherapy or autologous HSCT in adults as well and children with AML in first remission. These studies have demonstrated that allogeneic HSCT is superior to the other forms of post-remission therapy in children with AML not carrying favourable cytogenetic characteristics. We herein report the long-term results of a prospective multicenter study aimed at evaluating the safety and efficacy of an original combination of 3 alkylating agents, busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) as conditioning regimen for patients affected by de novo AML other than the FAB M3 subtype and given allogeneic HSCT from a matched family donor in first haematological CR. Patients and methods. Seventy consecutive patients (40 males and 30 females), affected by de novo AML in first CR, received an allogeneic HSCT from a HLA-matched family donor after a conditioning regimen combining BU (4 mg/Kg/day for 4 days), CY (60 mg/Kg/day for 2 days) and L-PAM (140 mg/m2). BU dosage was adjusted after the pharmacokinetic study performed following the first administration, in order to maintain a concentration to the steady state (Css) comprised between 600 and 900 ng/mL. Transplants were performed in one of the transplant centers of the Italian Association for Pediatric Hematology / Oncology (AIEOP) between 1992 and 2002. Median patient age at HSCT was 7 years (0.5 – 17). Two patients had FAB M0 AML, 25 M1, 17 M2, 12 M4, 21 M5, 1 M6 and 2 M7 AML. Children with M3 AML were excluded from the study. Five patients with CBF anomalies, either isolated or associated with loss of sex chromosome, were considered to have favourable cytogenetics. The median interval between diagnosis and HSCT was 3.9 months (2.9 - 9). All patients were given bone marrow stem cells. GVHD prophylaxis consisted of cyclosporine-A (Cs-A) alone in 89% of patients, the remaining children receiving a combination of Cs-A with short-term methotrexate. Results. Median follow-up for surviving patients is 9 years (range, 6 – 16 years). The conditioning regimen was well tolerated, and no patient died for causes directly attributable to the myeloablative treatment. All patient engrafted, the median time to reach neutrophil and platelet recovery being 13 (7 - 28) and 21 (13 – 115) days, respectively. The cumulative incidence (CI) of grade II-IV acute GVHD was 58% (48 – 71), while that of grade III-IV acute GVHD was 14% (8 – 25). Chronic GVHD incidence was 27% (18 – 39). Ten-years survival probability was 77% (67 - 87), while 10-years disease-free survival (DFS) was 76% (65 - 86). The cumulative incidence of relapse was 17% (10 – 29), while the cumulative incidence of transplant-related mortality was 7% (3 – 17). Results improved over time, DFS being 59% (41 – 78) for patients transplanted before 1997 and 86% (75 – 96) for those transplanted after 1997. No other variables influenced the probability of both survival and DFS. Conclusions. Our study, conducted on a significant number of children affected by AML in first CR and with a very long follow-up demonstrate that allogeneic HSCT from a matched family donor can cure a large proportion of patients. The combination of dose-adjusted BU, CY and L-PAM was safe and well tolerated, with an incidence of TRM of only 7% and no death directly attributable to the conditioning regimen. Furthermore, the combination of 3 alkylating agents showed a good anti-leukemic activity, the probability of leukaemia recurrence being only 17%. Disclosures: No relevant conflicts of interest to declare.

Superior survival associated with transplantation of matched unrelated versus one-antigen–mismatched unrelated or highly human leukocyte antigen– disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 806-814 ◽  
Author(s):  
William R. Drobyski ◽  
John Klein ◽  
Neal Flomenberg ◽  
Daniel Pietryga ◽  
David H. Vesole ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Treatment Algorithm ◽  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Leukocyte Antigen ◽  
Significant Difference ◽  
Family Donor

Abstract The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one- antigen–mismatched unrelated, or highly human leukocyte antigen (HLA)–disparate family donors. Between 1993 and 2000, 139 patients underwent transplantation from unrelated donors (81 matched and 58 mismatched) and 48 patients received marrow grafts from family donors that were mismatched at 2, 3, or 4 of 8 HLA loci. All patients received a standardized conditioning regimen and a graft-versus-host disease (GVHD) prophylaxis schedule with the exception of recipients of haploidentical marrow grafts, who received antithymocyte globulin after bone marrow transplantation as additional immunosuppression. There was no statistically significant difference in the rate of engraftment, or the cumulative incidences of acute and chronic GVHD between any of the 3 groups. The 2-year cumulative incidence of relapse was lower in matched unrelated patients (25%, P = .01) and mismatched unrelated patients (26%,P = .014) than in haploidentical patients (42%). Transplant-related mortality was significantly higher in recipients of mismatched unrelated grafts (45%, P = .01) and haploidentical grafts (42%, P = .001) compared with recipients of matched unrelated marrow grafts (23%). This resulted in a significantly higher probability of overall survival for matched unrelated patients (58%) versus either mismatched unrelated (34%,P = .01) or haploidentical (21%, P = .002) patients. There was no statistically significant difference in survival between patients who received mismatched unrelated grafts versus those who received haploidentical grafts. This study supports a donor selection algorithm whereby patients who lack a closely matched family donor be offered a phenotypically matched unrelated donor if available. There is no apparent advantage to using a mismatched unrelated versus a highly HLA-disparate family donor.

A Fludarabine Based Conditioning Regimen Associated with A Good Survival Following HLA Identical Sibling/Family Donor Transplants in Patients with Aplastic Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1194-1194 ◽  
Author(s):  
Mammen Chandy ◽  
Biju George ◽  
Vikram Mathews ◽  
Shashikant Apte ◽  
Velu Nair ◽  
...  
Keyword(s):  
Overall Survival ◽  
Aplastic Anemia ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Risk Group ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Transplant Recipients ◽  
Primary Graft Failure ◽  
Family Donor

Abstract Abstract 1194 Poster Board I-216 Between January 2001 and June 2009, 120 patients with aplastic anemia underwent HLA identical sibling or family donor transplants using a combination of Fludarabine 150-180 mg/m2 over 5 days and Cyclophosphamide 120 mg/kg over 2 days as the conditioning regimen. Antithymocyte globulin (ATG) 10 mg/kg x 4 days in addition was used in 34 patients. Graft versus host disease (GVHD) prophylaxis consisted of Cyclosporine with low dose Methotrexate. Graft source included peripheral blood stem cells (PBSC) in 108 and G-CSF stimulated bone marrow in 12. Seventy patients (58.3%) were considered as high risk (presence of fever/infection at time of HSCT or >20 transfusions prior to HSCT or failed previous immunosuppressive therapy). There were 79 males and 41 females with a median age of 22 years (range: 2 - 51) including 36 children (age <15 years). PBSC was used in 108 while BM was the graft source in 12. The median cell dose infused was 7.1 × 108 MNC/Kg for PBSC (range: 1.9 – 19.6) and 4.9 × 108 TNC/Kg for bone marrow (range: 2.1 to 9.9). One hundred and thirteen patients (94.1%) engrafted while 2 (1.6%) had primary graft failure and 5 expired within the first 2 weeks due to infection. The median time to neutrophil engraftment (ANC > 0.5 × 109/L) was 12 days (range: 7-19) while platelet engraftment (Platelet count > 20 × 109/L) occurred at a median of 13 days (range: 0 -30). Acute GVHD occurred in 38 patients (33.3%) with grade III-IV GVHD in 13.1%. Acute GVHD was not significantly lower in patients where ATG was used in conditioning (21.8% with ATG vs 38.2% without ATG; p = 0.129). Nine patients (7.5%) had veno-occlusive disease of the liver while 11 (9.1%) had hemorrhagic cystitis; all responded well to supportive therapy. Bacterial infections were documented in 28% of transplant recipients while fungal infections (both probable and definite) occurred in 23%. CMV reactivation was seen in <5%. Chronic GVHD occurred in 32.6% of evaluable transplant recipients and was limited in a majority of patients. At a median follow up of 30 months (range: 1 – 105), 88 patients (73.3%) are alive and well. Causes of death included sepsis in 19, acute GVHD in 7, chronic GVHD in 4, primary graft failure in 1 and road traffic accident in 1 patient. The overall survival was similar among children (75%) and adults (72.6%). The overall survival was significantly lower in the high risk group (60%) compared to the low risk group (92%; p = 0.0001). Conclusion: A combination of fludarabine and cyclophosphamide as conditioning for aplastic anemia is associated with good engraftment, a very low incidence of primary or secondary graft failure and good overall survival. Toxicity is low but acute and chronic GVHD remain significant problems. Sepsis continues to remain the major cause of death in these patients. Disclosures: No relevant conflicts of interest to declare.

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