A Phase I-II Dose Escalation Trial of Clofarabine Plus Melphalan and Thiotepa Followed by Unmodified Allogeneic Stem Cell Transplant (SCT) for the Treatment of High Risk or Advanced Acute Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2354-2354
Author(s):  
Farid Boulad ◽  
Nancy A Kernan ◽  
Susan E Prockop ◽  
Andromachi Scaradavou ◽  
Trudy N Small ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Phase I ◽  
Dose Level ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Acute Leukemias ◽  
Unrelated Donors ◽  
Disease Free

Abstract Abstract 2354 High-risk or advanced acute leukemias are associated with poor outcome even with the use of stem cell transplantation (SCT) with or without total body irradiation (TBI). Based on encouraging results with the use of clofarabine (CLO) for reinduction treatment of acute leukemias, we have developed a phase I/II protocol using this agent with melphalan (Mel) and thiotepa (Thio) followed by unmodified SCT for the treatment of patients (pts) with high-risk (HR) leukemias. To date, 28 consecutive pts were treated on, or as per protocol, with 26 pts evaluable for follow-up. There were 15 males and 11 females aged 1–58 years (median 5.3 years). Cytoreduction consisted of CLO at dose level I of 20 mg/m2/day × 5 days (n=23) or at dose level II of 30 mg/m2/day × 5 (n=3), Thio 10 mg/Kg/day × 1 day and Mel 70 mg/m2/day × 2 days. Graft-versus-host disease (GvHD) prophylaxis consisted of tacrolimus and mycophenolate mofetil (MMF), or tacrolimus and methotrexate. Twenty pts had acute lymphoblastic leukemia (ALL) in complete remission (CR1; n=5), CR2 (n=5), CR3 (n=9), or relapse (n=1). Five pts had acute myeloid leukemia (AML), in CR1 (n=1), CR2 (n=2), or CR3 (n=2). One pt had myelodysplastic syndrome (MDS) in RAEB. For the pts with ALL in CR1, very HR features included: Infant MLL (N=2), Philadelphia (Ph1) chromosome (N=2) and Induction failure (N=1). For the pts with ALL in CR2, HR features included: Infant MLL (N=1), 2nd SCT (N=1), Ph1 and 2nd SCT (N=2), while 1 pt had prior CNS infarcts precluding the use of TBI. The one pt with AML in CR1 had M7-AML. This was a first SCT for 14 pts, a 2nd SCT for 11 pts and 3rd SCT for 1 pt, with time from previous SCT to the present one being 5–73 months (median 11.3 mo) for those 12 pts. Donors were HLA-matched siblings (n=8), HLA matched unrelated donors (n=8), or HLA mismatched unrelated donors (N=10). Stem cell grafts were bone marrow (n=12), peripheral blood (n=7) or double cord blood (n=7) stem cells. Twenty four of the 26 evaluable pts engrafted, while 2 pts died prior to engraftment. Toxicity of the SCT cytoreduction included elevation of hepatic transaminases in 17 of 26 evaluable pts (AST elevation of 5–19 fold and ALT elevation of 7–16 fold), with a subsequent normalization in all pts. Mucositis was mostly at acceptable grade 1–2 levels. Two pts developed a syndrome of renal and hepatic insufficiency leading to hepatic veno-occlusive disease (VOD) (1 pt at each of the 2 dose levels). Non-relapse mortality included: VOD (N=2), infections (N=3), treatment related sarcoma, a malignancy secondary to the irradiation received with a prior transplant (N=1). With a follow-up of 3–57 mos (median 21 mos), 15 of the 26 pts are alive, disease-free. Five pts relapsed and 4 died subsequently of disease, while 6 pts died of non-relapse morality. Overall (OS) and disease-free survival (DFS) at 2 years were both 58%. DFS was 56% for pts > 18 years and 53% for pts < 18 years (p =0.36); it was 64% for recipients of a first HSCT and 41% (p=0.97) for recipients of a second or third HSCT. Five pts (4 recipients of unrelated donor SCT; 3 from mismatched donors) developed Grade 2–4 acute GvHD. Four of these pts went on to develop chronic GvHD. Immune reconstitution was rapid; for the evaluable pts, it included absolute CD4 counts > 200 cells/L at 1–3 mos for 15 pts and at 4–8 mos for 4 pts. This cytoreductive regimen represents a promising approach for the transplantation of patients with high risk acute leukemias. It was well tolerated for pts requiring a second SCT and is also associated with rapid immune recovery. Ultimately, a large scale study would need to be done to determine if this approach could offer equal or superior results to TBI containing regimens for ALL or AML. Disclosures: No relevant conflicts of interest to declare.

Phase I Study of Triapine® and Cytarabine (ara-C) in Patients with Relapsed or Refractory Acute Leukemias and High-Risk Myelodysplastic Syndrome (MDS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4925-4925
Author(s):  
Karen W.L. Yee ◽  
Jorge Cortes ◽  
Guillermo Garcia-Manero ◽  
Srdan Verstovsek ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Maximum Tolerated Dose ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
Acute Leukemias ◽  
Elevated Liver Enzymes ◽  
Synergistic Cytotoxicity

Abstract Triapine is a potent inhibitor of ribonucleotide reductase (RNR), which is required for the conversion of ribonucleotides to deoxyribonucleotides. Two phase I trials in patients with hematologic malignancies demonstrated that Triapine could reduce circulating blasts in the majority of patients without significant non-hematologic toxicity (Giles et al. Leuk Res2003;27:1077–1083; Karp et al. Blood2002;100:560a). Preclinical studies have shown that the combination of Triapine and ara-C produces additive or synergistic cytotoxicity against several tumor cell lines, potentially by increasing intracellular ara-CTP levels when Triapine inhibits RNR. Therefore, a phase I study of Triapine in combination with ara-C was conducted in 32 patients with relapsed or refractory acute leukemia and high-risk MDS (1 MDS, 28 AML, 2 Ph+ ALL, and 1 Ph- ALL) in order to determine the tolerability, safety, and maximum tolerated dose (MTD). Triapine® was administered at a dose of 105 mg/m2/d as a 6-hour infusion for 5 consecutive days (D1–5) followed immediately by ara-C [100 (n=4), 200 (n=6), 400 (n=7), or 800 (n=8) mg/m2/d] as an 18-hour infusion for 5 consecutive days (D1–5). Median age was 59 years (range, 15–83 years). Median ECOG status 1 (range, 0–2). Median number of prior therapies was 2 (range 1–9), including prior autologous (n= 2) and allogeneic stem cell transplant (SCT) (n=4). Dose-limiting toxicities (DLTs) were observed at the 800 mg/m2 ara-C dose level (1 patient each with grade 4 mucositis; grade 4 neutropenic colitis, sepsis and death; grade 4 neuropathy; and grade 4 hyperbilirubinemia). Therefore, the study was amended to include an ara-C dose level of 600 mg/m2/d. Seven patients were treated at this dose level without development DLTs. Thirty-one patients received at least 1 course, 2 received 2 courses, and 4 received 3 courses; 1 patient withdrew prior to completion of 1 course of therapy. Of the 31 evaluable patients, 4 (13%) patients (3 AML, 1 Ph+ ALL) achieved a CR (1 at an ara-C dose of 800 mg/m2; 2 at 600 mg/m2; 1 at 200 mg/m2). Two of the responders also achieved a complete cytogenetic remission (including 1 Ph+ ALL). All responses occurred after 1 induction course. One patient went on to receive an allogeneic (SCT) and continues in CR. Duration of responses was 9, 20, 52+, and 73+ weeks. Mean Cmax and AUC achieved for Triapine were 1.13 μg/mL and 251.5 min•μg/mL. The most frequent toxicities included nausea &/or vomiting (66%), elevated liver enzymes (50%; gr. 3 in 22%), fever (47%), diarrhea (41%; gr. 3 in 6%), rash (31%; gr. 3 in 6%), mucositis (28%), hand-foot syndrome (16%; gr. 3 in 3%), and peripheral edema (16%; gr. 3 in 9%). Triapine and cytarabine has activity in patients with relapsed or refractory acute leukemias. The recommended phase II dose is Triapine 105 mg/m2/day for 5 consecutive days (D1–5) followed by ara-C 600 mg/m2/d for 5 consecutive days (D1–5).

Molecular Relapse of Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation Can Be Successfully Treated with Donor Lymphocyte Infusions.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5122-5122
Author(s):  
Alida Dominietto ◽  
Anna Maria Raiola ◽  
Raffaella Grasso ◽  
Anna Garuti ◽  
Carmen di Grazia ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Donor Lymphocyte Infusions

Abstract Background. Hematologic relapse is seen in 20–40% of adult acute lymphoblastic leukemia (ALL) patients undergoing an allogeneic hematopoietic stem cell transplant (HSCT) and is usually non responsive to donor lymphocyte infusions (DLI). This has suggested a lack of graft vs leukemia effect (GvL) in ALL patients. It is currently possible to monitor minimal residual disease (MRD) post-HSCT and this may allow to identify patients at high risk of hematological relapse. Objectives. To monitor MRD in B-ALL patients post-HSCT and to treat MRD positive patients with DLI. Patients and Methods. MRD was evaluated on bone marrow samples using nested polymerase chain reaction (PCR) and real time PCR (RT-PCR) assay to analyze respectively IgH VDJ and BCR-ABL gene rearrangement. Molecular positivity/relapse was defined with two consecutive positive PCR assays. MRD monitoring was performed in 28 patients grafted from an HLA-identical sibling (n=19), family mismatched related donor (n=2) or matched unrelated donor (n=7). Median follow-up was 47 months (range 5–163). Sixteen patients (57%) were in early disease phase at the time of transplant. Results. We identified 3 groups of patients. A) 14 patients (50%) had no evidence of MRD after HSCT. B) 6 (21%) had a positive MRD and received escalating dose DLI, within 60 days and C) 8 (29%) had a positive MRD, but did not received DLI, because not available or because of an early hematological relapse. Median time from HSCT to molecular relapse was 139 days (range 46–1048). The median follow up was 1385 days (144 – 4877). Median number of infused CD3+ cells was 0.6x10^7/Kg of recipient body weight (range 0.01–7). Hematological relapse was seen in 0%, 0% and 88% respectively of group A,B,C (p=0.0001) and disease-free survival (DFS) was 100% , 67% , 12% (p=0.0001). Conclusions. This study shows that (1) MRD monitoring of ALL patients post-transplant identifies patients at high risk of hematologic relapse and (2) that treatment with DLI, on the basis of MRD positivity, significantly reduces the risk of leukemia relapse and may improve DFS. These data also confirm the existence of a GvL effect, previously shown in this disease (Weiden et.al NEJM, 300, 1068; 1979).

Comparative 2-Arm Study for Acute Graft-Versus-Host Disease; Antithymocyte Globulin Is More Effective Than Mycofenolate Mofetil on Outcome of Allogeneic Peripheral Blood Stem Cell Transplantation from Mismatched Unrelated Donors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5395-5395
Author(s):  
Woo-Sung Min ◽  
Heeje Kim ◽  
Byoung-Sik Cho ◽  
Sung-Yong Kim ◽  
Ki-Sung Eom ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Group A ◽  
Unrelated Donors ◽  
Group B

Abstract We have experienced many HLA-mismatched unrelated donor hematopoietic stem cell transplantation (HSCT) for patients with high-risk AML. The availability of unrelated donors, who were categorized as high-risk for acute GvHD posttransplant, based on well understanding of impact of HLA allele or antigen mismatch immunobiology on various clinical outcomes, was investigated. With the use of different immunosuppression conditioning regimens, according to the patient-risk grouping, will allow stable HLA-mismatched unrelated donor HSCT to meet the needs best of the individual patient. Beginning on March 2004, 23 consecutive adult patients were enrolled in treatment protocols and follow-up was carried out through July 31, 2006. Patients with AML, age in the range between 17 and 58, who were all in 1st or 2nd complete remission, had high-risk assessment, in various performance status, received mainly total body irradiation containing conventional myeloablative transplantation. Specifically, for patients who were supposed to receive peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors at the level of HLA antigen (N=5) or 1-2 alleles (N=7) at the HLA-A, B, Cw, and DR loci; if antithymocyte globulin (ATG;Thymoglobulin, SangStat), at a dose of 1.25 mg per kilogram of body weight per day, was given intravenously on days D-3 and D-2 followed by FK-506 from D-1 and short-term methotrexate at D+1, D+3, D+6, D+11 at a dose of 5mg/m2 intravenously, they were enrolled as group A (N=10). In contrast, if mycofenolate mofetil was started from D+21 and tapered out until D+60 instead of ATG, they were in the group B (N=13). Patients with unrelated donors were screened for HLA-A, B, and DRB1 alleles with the use of high-resolution (DNA sequencing) molecular typing method. Median age for group A, B were 36 (range, 17–58), 32 (range, 17–48), respectively. Sex ratio was similar between 2 groups. Group A received with a median CD34 dose of 4.2 (3.6–8.8) ×106/kg compared with 2.4 (1.6–5.5) ×106/kg of the group B. Median time to neutrophil (>0.5×109/kg) and platelet (>20×109/kg) regeneration was 13 vs 15 days, 14 vs 17 days in the group A and B respectively. After median follow-up of 9 months (range, 2–20) and 16 months (range, 3–29) for each group, acute GvHD was observed in 40% and 77%, respectively. However, 31% was greater than grade II acute GvHD in the group B and one of them died due to severe GvHD grade IV, despite none (0%) in the group A. Only 2 patients (29%) in the group A developed limited type chronic GvHD, but 3 patients in the group B together with 3 of extensive type (46% in total). Also, one case of graft rejection was observed in the group B (4%). The cumulative incidence of each group transplant related mortality (TRM) was 0% and 15%, respectively. The relapse rate was 0% in each group. Therefore, in our experience, in order to reduce TRM using unrelated donor PBSCs, particularly in the HLA-mismatched setting, it is required to cautiously apply ATG as a critical immunosuppression used in this group A as the benefits from reduction of GvHD/rejection.

Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning (RIC) Regimen Has the Capacity To Produce Durable Remissions and Long Term Disease-Free Survival in Patients with High Risk Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1141-1141
Author(s):  
S. Tauro ◽  
S. Mackinnon ◽  
K. Peggs ◽  
G. Begum ◽  
P. Mahendra ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract The toxicity of allogeneic stem cell transplantation (SCT) can be substantially reduced by the use of a reduced intensity conditioning (RIC) regimen and this has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with AML and MDS has not yet been defined and consequently their role in the management of these diseases remains conjectural. Seventy-six patients with high risk AML or MDS were allografted using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range 18–71 years). There were 46 males and 30 females; 41 patients received an allograft from an unrelated donor and 35 from a matched sibling donor. The 100 day transplant related mortality was 9% and no patient developed greater than Grade 2 graft-versus-host disease (GVHD). With a median follow-up of 36 months (range 13–70 months) 27 patients were alive and in remission with a 3y actuarial overall survival (OS) and disease-free survival (DFS) rate of 41% and 37% respectively. The 3y OS and DFS of patients with AML in complete remission (CR) at the time of transplantation was 48% and 42% respectively. In a multivariate setting, Cox regression analysis demonstrated prognostic significance of disease stage at the time of transplant with improved DFS in patients with AML in CR at the time of transplantation (HR=2.03, 95% CI=1.02–4.07). Disease relapse was the commonest cause of treatment failure occurring at a median time of 6 months post-transplant. Fourteen out of 27 (52%) patients relapsed within 6 months and 23/27 (85%) within twelve months defining a relatively narrow window for therapeutic intervention to prevent disease recurrence. The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts are capable of producing sustained disease free survival in a significant number of patients with AML who would be ineligible for allogeneic transplantation using a myeloablative conditioning regimen.

Results of T Cell Depleted (TCD) Myeloablative Hematopoietic Stem Cell Transplants (HSCT) in Patients with Hematologic Malignancies ≥ 55 yrs of Age.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3660-3660
Author(s):  
Ann A. Jakubowski ◽  
Esperanza B. Papadopoulos ◽  
Hugo R. Castro-Malaspina ◽  
Katharine Hsu ◽  
Miguel-Angel Perales ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
High Risk Patient ◽  
Disease Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Conditioning Regimens ◽  
Good Risk

Abstract Allogeneic HSCT remains the only curative therapy for many patients(pts) with hematologic diseases. Studies have suggested that older pts experience greater toxicity from the intensive chemo-radiotherapy used in myeloablative conditioning regimens. As a consequence, many older pts are now offered non-myeloablative transplants (NMAT) for malignant conditions where a graft vs. tumor effect (GvT) is expected to provide the antitumor effect in place of the chemo-radiotherapy. Unfortunately, graft vs. host disease (GvHD) remains a common occurrence after conventional transplants, occurring more frequently in older pts and unrelated donor transplant recipients, resulting in significant morbidity and mortality. Furthermore, the efficacy of NMAT is limited by the disease status at time of transplant and by the susceptibility of the hematologic disease to a GvT effect. TCD of hematopoietic stem cell grafts offers an alternative to older pts, in particular those requiring unrelated donor transplants (URD), with the advantage of a reduced incidence of GvHD. From 1995–2005, 57 patients ≥55 yrs received myeloablative TCD transplants at our institution. The median age was 58.2 (range 55–69.2) yrs. Stem cell sources were TCD bone marrow, PBSC or both. Thirty-seven received transplants from related donors (RD), including two mismatched, and 20 received transplants from unrelated donors (URD), 9 of whom were mismatched. In addition to their advanced age, many of these pts were considered high risk based on the status of disease, HLA mismatch, and history of previous therapy. Twenty-three pts were considered “good risk” by disease status (CML-CP1, AML-CR1, CR2) and 34 pts were considered poor risk (&gt;CML-CP1, &gt;AML CR2, MDS, NHL, &gt;ALL CR1, ABL.) BM was TCD by soybean agglutination followed by sheep red blood cell rosetting (E), and PBSCs by CD34+ selection and E-rosetting. Conditioning regimens included total body irradiation (TBI) in addition to thiotepa and cyclophosphamide, or thiotepa and fludarabine. The non-TBI preparative regimen consisted of busulphan, melphalan and fludarabine. Anti-thymocyte globulin was used as rejection prophylaxis for all TCD transplants until 2001 when it was eliminated from the TBI containing regimen for matched RD transplants. A total of 25 pts (15 matched RD and 10 URD, 6 of whom were mismatched) are alive following TCD transplants with a median follow up of 24 mos. for RDs and 12 for URDs. Of the survivors, 2/10 URD and 14/15 RD recipients received TBI containing regimens based on the triage system at our center. Three pts with CML-CP1, one with CML-acc and one with AML-CR1 showed evidence of minimal residual disease, received donor leukocyte infusions and subsequently achieved longterm continued CR. The incidence of post-transplant GvHD was low despite the high number of mismatched URD transplants - 1 Grade IV (RD), 2 Grade 3 and 1 Grade 1 (URD). The 100 day mortality was 15%. Overall and current disease free survival for ‘good risk’ patients based on disease status is 58% for RD and 60% for URD. Although longer follow up is necessary to confirm these results, the promising DFS rates in association with a low incidence of GvHD in this older and relatively high risk patient population support further investigation of myeloablative TCD HSCT in these patients.

Voriconazole for Secondary Prophylaxis of Invasive Fungal Infection in Allogeneic Stem Cell Transplant Recipients: Results of the VOSIFI Study. on Behalf of the VOSIFI Study Group and the Infectious Diseases Working Party of the European Bone and Marrow Transplantation Group.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1159-1159 ◽  
Author(s):  
Catherine Cordonnier ◽  
Hermann Einsele ◽  
Montserrat Rovira ◽  
Johan Maertens ◽  
Eduardo Olavarria ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Secondary Prophylaxis ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Adequate Treatment ◽  
Post Transplant ◽  
The Mean

Abstract Background: Despite adequate treatment and favorable initial outcome, the risk of recurrence of a previous invasive fungal infection (IFI) or acquisition of a new one is a major obstacle to the success of stem cell transplantation (SCT). The rate of IFI relapse is estimated to be 30 to 50%. Secondary prophylaxis could increase survival and reduce the burden of fungal infections to these patients. Methods: A prospective open multicenter trial was performed to evaluate the efficacy of voriconazole (VORI) (4mg/kg/12h IV or 200mg/12h oral) as secondary prophylaxis in allogeneic SCT patients with previous proven or probable IFI (2002 EORTC/MSG consensus criteria). Adult patients (Age &gt; 18 y) were eligible if the prior IFI had occurred within the 12 months prior to SCT. Exclusion criteria were prior resistance to VORI, prior history of zygomycosis, or active IFI at time of transplant. VORI was started within 3 days before transplant and planned for 100 days. Prophylaxis could be prolonged up to 150 days in case of persistent graft-versus-host disease (GVHD) and ongoing immunosuppression on day 100. All patients were followed until 12 months post-transplant, or until death, whichever occurred first. The primary endpoint was the rate of proven and probable IFI between the start of VORI prophylaxis and the 12 month follow-up. Diagnosis of prior IFI, diagnosis of IFI occurring during the study, and cause of deaths, were assessed by a Data Review Committee including an independent radiologist. Results: 45 patients from 17 EBMT centers were included from Feb 2005 to March 2007. The mean age was 48 y (22–72). Forty-one had acute leukemia, and 24 were in first complete remission. Previous IFI included proven (n= 6) or probable (n=26) aspergillosis, proven candidiasis (n=5), and others (n=8). The mean time from diagnosis of the previous IFI to SCT was 151 days. Twenty four patients were transplanted from a family donor (HLA-id: 18; mismatched: 5; twin: 1), and 21 from an unrelated donor. The graft was bone marrow (n=6), peripheral blood stem cells (n=38) or cord blood (n=1). The conditioning regimen was myeloablative in 27 and non myeloablative in 18 patients. The median follow-up was 360 days (range 5–469). Twenty-six (58%) patients experienced at least one episode of GVHD. Three cases of IFI were recorded after transplant: one C. albicans candidemia, one S prolificans fungemia and one zygomycosis, at day 3, 16, and 66 after transplant, respectively (incidence: 7%). Two of these 3 IFI were relapses of a previous IFI. The median duration of the VORI prophylaxis was 94 days (5–180). Eleven patients (24%) died between 96 and 326 days post-transplant (median: 136 days) from scedosporiosis (n=1), leukemia relapse (n=4), respiratory failure or pneumopathy of unknown origin (n=3), GVHD (2), or sepsis (n=1). Conclusion: Voriconazole appears to be an efficient drug for secondary prophylaxis of proven and probable IFI after allogeneic SCT, with few adverse events. Considering an expected rate of IFI occurrence or recurrence after transplant of around 30%, the observed rate of 7%, and only one death from IFI in this high-risk adult population are promising.

Low Relapse without Excessive Transplant-Related Mortality Following Allogeneic Stem Cell Transplantation in Patients with High Risk Secondary Acute Myeloblastic Leukaemia and Myelodysplastic Syndromes, Long-Term Outcomes in a Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4308-4308
Author(s):  
Jean El-cheikh ◽  
Luca Castagna ◽  
Sabine Furst ◽  
Catherine Faucher ◽  
Benjamin Esterni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Allogenic Stem Cell Transplantation ◽  
Related Mortality

Abstract Abstract 4308 Allogenic stem cell transplantation (Allo-SCT) as a therapy for secondary acute myeloid leukaemia (sAML) and myelodisplastic syndromes (MDS) is the most powerful treatment option. However, (Allo-SCT) is also complicated by a high risk for treatment-related morbidity and mortality. We analysed retrospectively the data of 70 patients transplanted at our institution from June 1995 to december 2008, 44 patients (63%) with sAML and 26 patients (37%) with MDS was treated with (Allo-SCT); median age at diagnosis was 41 years, (15-70), and the median age of 42, 5 years (16-70) at transplantation; The conditioning regimen was myeloablative combining (cyclophosphamide and TBI) in 16 patients (23%) and 54 patients (77%) was with a reduced intensity conditioning (RIC) regimens combining fludarabine, busulfan, and antithymocyte globulin; 11 patients (16%) were infused with bone marrow (BM), 55 patients (79%) peripherical blood stem cells (PBSC), and 4 patients (5%) cord blood cells; in 49 cases (70%) donor was a HLA identical sibling and in 21 (30%) was a matched unrelated donor; 41 patients (59%) carried high risk cytogenetic features, like (7q-, 5q-, > 3 alterations), while was normal in 24 patients (34%), and in 5 patients (7%) was unknown. Disease status at transplantation was as follow: CR in 24 patients (34%), 34 patients (49%) was refractory or in progression after treatment, and 12 patients (17%) was with a stable disease. With a median follow-up of 55 months (3-150), 30 patients (43%) are alive, the overall survival OS at 2 years and 5 years was 48 % and 39% respectively, and after ten years of follow up, OS was 30%, 95%CI [17.8-50.8]. We observed also that 26 % of refractory patients and 54% of patients in CR are alive at five years of transplantation. The probability of progression after transplantation at five and ten years was 31% with 95%CI [20.-46.5]. 2 years and 5 years treatment related mortality (TRM) was 23% and 26% respectively, and no modification at ten year, 95%CI [14.3-37.3]. TRM occurred in 16 patients (23%). Cause of death was; infections in 5 patients (7%), GvHD in 3 patients (4%), GvHD and infection in 3 patients (4%), multi organ failure (MOF) in 5 patients (7%). In multivariate analysis; OS, PFS or TRM, were not influenced by donor type (HLA id sibling vs others), conditioning regimen (RIC vs MAC), and stem cell source (bone marrow vs PBSC). Allogenic stem cell transplantation can be considered as a good option for the treatment of patients with high risk sAML and MDS when compared with the remission rate at five years of the other nonallogeneic SCT therapies. Disclosures: No relevant conflicts of interest to declare.

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