A Randomized Trial of Bone Marrow (BM) Versus Peripheral Blood (PB) Allogeneic Hemopoietic Stem Cell Transplants (HSCT) in Patients with Myeloproliferative Disorders.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2998-2998
Author(s):  
Andrea Bacigalupo ◽  
Maria Teresa van Lint ◽  
Attilio Olivieri ◽  
Marco Casini ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Randomized Trial ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Myeloproliferative Disorders ◽  
Hemopoietic Stem Cell ◽  
Term Survival

Abstract Background. Reduced intensity conditioning (RIC) regimens have been widely used over the past years with the aim of reducing transplant related mortality (TRM) of allogeneic hemopoietic stem cells transplants (HSCT). The preferred source is peripheral blood (PB) cells, although this source has not been prospectively compared with bone marrow (BM) iun the setting of RIC transplants. Aim of the study. To compare BM and PB allogeneic transplants following a RIC regimen in patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML) or idiopathic myelofibrosis (IM). Methods and patients. This is a prospective multicenter randomized trial: eligible were patients with AML, CML and IM, aged 45–60, with an HLA identical sibling, Conditioning regimen was thiotepa 5 mg/kgx2 and cyclophopshamide 50 mg/kgx2. Graft versus host disease (GvHD) prophylaxis was low dose cyclosporin and low dose methotrexate. Patients were randomized to receive unmanipulated BM (n=36) or unmanipulated PB (n=35), after stratification for disease phase (1st remission, n=47) or advanced disease (n=24). Median age was 51 in both groups and follow up of surviving patients 760 and 756 days respectively. Results. Engraftment was achieved in all but one patient who has autologous reconstitution. Acute GvHD grade III–IV accurred in 0% vs 12% of BM vs PB patients (p=0.03) and extensive chronic GvHD in 13% vs 37% respectively (p=0.03). Cumulative incidence (CI) of TRM at 5 years is 6% for BM and 9% for PB (p=0.6). Relapse of the original disease occurred in 61% vs 29% of BM and PB patients (p=0.007) and the CI of relapse related death (RRD) is 39% vs 19% respectively (p=0.07). Actuarial 5 year survival is 47% in BM vs 68% in PB paitents (p=0.3). A COX proportional step down analysis shows chronic GvHD to be a significant favourable factor for RRD and survival. Conclusions. In patients receiving a RIC allogeneic graftTRM is low and comparable in BM and PB transplanst;acute and chronic GvHD is more frequent in PB transplants,relapse is significantly decreased in PB transplants and RRD is also lower,there is a non significant survival advantage for PB patients andthe occurrence of chronic GvHD protects against relapse and favourably influences long term survival.

Allogeneic Stem Cell Transplantation For Patients With Adrenoleukodystrophy. Nationwide Retrospective Study In Japan

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2148-2148
Author(s):  
Koji Kato ◽  
Hiromasa Yabe ◽  
Shunichi Kato ◽  
Souichi Adachi ◽  
Yoshiko Hashii ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Low Dose ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Transplant Outcome

Abstract Introduction Adrenoleukodystrophy (ALD) is an autosomal recessive disorder with progressive neurodegeneration caused by the mutation of ABCD1 gene and allogeneic stem cell transplantation (SCT) at its early stage is recognized as the only effective treatment modality to control the neurological symptoms. But the transplant outcome according to the conditioning regimen is not well understood so far. Here we analyzed the transplant outcome of patients with ALD using the clinical data accumulated in the Japan Society of Hematopoietic Cell Transplantation and tried to find the favorable conditioning regimen. Methods From 1988 to 2010, 76 patients with ALD were transplanted and their age at transplant was 1-34 years old (median 8). Stem cell sources the patients received were bone marrow (sibling 26, non-sibling related donor 5, unrelated volunteer donor 17), and cord blood (sibling 1, unrelated 28). Conditioning regimen was classified into four categories of A: busulfan + cyclophosphamide +/- others, (n=25), B: melphalan + total lymphoid irradiation (TLI) / thoraco-abdominal irradiation (TAI) +/- fludarabine +/- anti-thymocyte globulin (n=23), C: fludarabine + melphalan +low dose total body irradiation (TBI) (n=18), and D: others (n=10). Results Sustained engraftment was obtained in 59 patients (77.8%) and it was significantly higher in bone marrow transplant (BMT) patients than cord blood transplant (CBT) patients (87.8% vs 60.7%, P=0.001). The incidence of acute graft-versus-host disease (GVHD), chronic GVHD and treatment related mortality of all patients were 7.9%, 19.3%, and 11.9%, respectively. Ten year overall survival (OS) and event free survival (EFS) of all patients were 83.7% and 64.1%, respectively. Ten patients died of either disease progression (n=2), or transplant related complications (n=8). Five year OS and EFS according to the conditioning regimen was A: 91.6% and 75.8%, B: 85.7% and 60.9%, C: 100% and 83.3%, D: 77.8% and 48.0%, respectively and they were not significant (P=0.379 in OS and P=0.183 in EFS, respectively). TBI was given to 22 patients with median dose of 4Gy (range 2-10.2) and sustained engraftment was obtained in 19 patients and all of 22 patients are alive. In patients who were not given TBI (n=54), 41 patients obtained engraftment and 44 patients are alive. OS according to presence or absence of TBI was 100% with TBI (n=22) and 86.1% without TBI (n=54) (P=0.091). By multivariate analysis for EFS, BMT and TBI were identified as good prognostic factors compared to CBT or non-TBI (HR 3.303, P=0.005, and HR 3.257, P=0.038, respectively), but OS of CBT was improved after 2005 compared to before 2004 (94.7% vs 68.6%, P=0.090). Conclusion Our results showed that conditioning regimen which includes TBI, even at low dose could provide better transplant outcome and the result of CBT improved after 2005 even though it was proved to be a significantly poor risk factor in the analysis of entire cohort. CBT enables urgent SCT when family donor is not available, and immediate transplant is essential for patients with ALD because of its nature. More precise assessment with brain MRI and neuropsychological examination is mandatory to evaluate the transplant outcomes of patients with ALD. Disclosures: No relevant conflicts of interest to declare.

Comparable Toxicity between Fludarabine/Full dose i.v. Busulfan and Fludarabine/Melphalan in Allogeneic PBSC Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5032-5032
Author(s):  
Sandeep Chunduri ◽  
Ellen Jessop ◽  
Lisa C. Dobogai ◽  
David Peace ◽  
Yogen Sanuthararajah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Single Dose ◽  
High Risk ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hemopoietic Stem Cell ◽  
Severe Thrombocytopenia ◽  
Cell Transplant ◽  
Full Dose ◽  
Small Series

Abstract Previous studies have demonstrated the efficacy of Fludarabine and full dose i.v. Busulfan as conditioning regimen in allogeneic hemopoietic stem cell transplant (HSCT). In this study we analyzed 22 patients who received an allogeneic HSCT from matched related (n=17) or unrelated (n=5) donors, and were conditioned with FLU/BU (fludarabine 30 mg/m2/d x 4 days followed by single dose i.v. busulfan 3.2 mg/kg/d x 4 days) (n=12) or FLU/MEL (fludarabine 30 mg/m2/d x 5 days and melphalan 70 mg/m2/d x 2 days) (n=10). Median age was 26 yrs (range:19–51) in the FLU/BU group and 47 yrs (range:22–57) in the FLU/MEL group (p=0.02). Also, patients at high risk were 8/12 in the FLU/BU group (7 AML in relapse, 1 CML-AP) and 3/10 in the FLU/MEL group (2 resistant NHL and 1 HD) (p=0.08). Patients received GVHD prophylaxis with FK-506 and MTX and in 9/12 FLU/BU cases (including 5 MUD) also with Thymoglobulin. HSC source was G-CSF mobilized peripheral blood in all FLU/MEL and 6/12 FLU/BU patients, while the remaining 6 received bone marrow cells. Median numbers of infused CD34+ cells were: 1.58 x 106/kg in FLU/BU patients receiving marrow grafts, while 5.0 and 5.9 x106/kg, respectively, in FLU/BU and FLU/MEL patients who received PBSC. Median time to ANC >500 was comparable in PBSC FLU/BU (d14, range: 11–20), and PBSC FLU/MEL (d12, range: 10–15) patients, while it was significantly longer in bone marrow FLU/BU (d 22, range:17–37) patients (p= 0.01 and p=0.001, respectively). Similarly, time to Plt >20K was d 12 (range: 10–16) in the PBSC FLU/MEL group and d 20 (range: 17–37) in the bone marrow FLU/BUS group. Interestingly, 4 of 6 PBSC FLU/BU patients did not have severe thrombocytopenia (<20K) after transplant. Mucositis > grade 2 was never observed in these two groups. Median length of stay (LOS) in the hospital after transplant was 17 days (range:13–37) in PBSC FLU/MEL, 23 days (range: 18–42) in PBSC FLU/BU and 30 d (range: 22–38) in bone marrow FLU/BU (p=n.s.). Median chimerism levels on d30 after transplant were: 100% in FLU/MEL and 95% in FLU/BU. One patient in the bone marrow FLU/BU experienced a graft rejection and was retransplanted succesfully. Median follow-up is 137 days (range: 42–548) in the FLU/BU group and 552 days (range: 157–633) in the FLU/MEL group. Acute GVHD was limited (grade 1 in 5/12 FLU/BU vs 1/10 FLU/MEL, and > grade 1 only in 1 FLU/MEL patient), and chronic GVHD is present in 1/4 FLU/BU and 4/9 FLU/MEL evaluable patients. Six of 12 patients in the FLU/BU died of: relapse (n=4) and/or infection (n=2, but only 1 within d100 ) and 3 of 10 patients in the FLU/MEL died, all of relapse. In conclusion, despite the small series of patients, the FLU/BU and FLU/MEL regimens seem to have similar limited toxicity in allogeneic PBSC transplantation. Due to its safety, an allotransplant conditioned with FLU/single dose i.v. BU could be applied also to elderly patients and may represent a platform for donor lymphocyte infusions in high risk patients.

Outcome of Busulfan and Fludarabine-Based Reduced Intensity Conditioning Regimen for Related and Unrelated HSCT in Fanconi Anemia Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1964-1964
Author(s):  
Saba Azarnoush ◽  
Raphael Porcher ◽  
Regis Peffault de la Tour ◽  
Karima Yakouben ◽  
Benedicte Bruno ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Low Dose ◽  
Acute Gvhd ◽  
Bone Marrow Failure ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Secondary Malignancy ◽  
Secondary Malignancies ◽  
Reduced Intensity

Abstract Abstract 1964 Rationale: HSCT is the only curative treatment for Fanconi Anemia (FA) pts with either bone marrow failure or MDS/Leukemia. Due to characteristic chromosomal instability, the poor outcome of FA pts transplanted after so-called conventional myelo-ablative conditioning regimen has been proved. Then, reduced-intensity conditionning regimen (RIC) has been considered for years as a model for allogeneic HSCT in FA pts. The use of fludarabine-based cond' regimen from about 2000 increased dramatically the overall survival of FA pts. Different Flu-based RIC were developed. Patients and method: Between Feb'02 and Dec'10, 17 FA pts from 3 academic French centers were included: 11 from R. Debre hospital, 5 from St Louis hospital and 1 from J. de Flandre hospital. All pts underwent HSCT because of bone marrow failure. They presented no MDS or leukemia. All time-to-event outcomes were counted from the date of HSCT to the date of event or date of last follow-up, except acute GVHD that was arbitrarily censored at 200 days. Death was considered as a competing risk in analyses of neutrophil and platelet recovery and chronic and acute GVHD. Overall survival was estimated using Kaplan-Meier product-limit estimator. For competing risks analyses, cumulative incidences were estimated using usual methodology. Results: Median age at diagnosis and at HSCT were 4.7 years (range 1,8-9,3) and 7,4 years (range 4,4-15,2), respectively. 12 pts presented with less than 3 FA-related malformations and 5 with more than 3 malformations. 2 patients received more than 20 transfusions before HSCT, whereas 8 pts received less than 20 transfusions and 7 patients did not received any. 2 patients received androgen therapy before HSCT. All patients received the same RIC i.e. fludarabine 30mg/m2/d × 3d, cyclophosphamide 10mg/kg/d × 4d and IV busulfan (Bu) 0.75 of body weight- adjusted recommended dose (equivalent to 6.4mg/kg total dose of oral Bu). This RIC did not contain any irradiation. Graft versus-host disease (GvHD) prophylaxis consisted of CSA associated with MMF or corticosteroids. Donors were either matched related (sibling, n= 6; other, n=2) or unrelated (10/10, n= 6; 9/10, n= 3). Stem cell sources were BM (n=10), UCB (n=4) and PBSC (n=2). 9 out of 17 pts had a donor from the same gender whereas 4 male recipients received transplant from female donor. CMV status were −/−, −/+, +/− and +/+ for 8, 4, 1 and 4 D/R pairs, respectively. Median follow-up was 32 months (range 3–102). Successful engraftment was obtained in all patients with a median time for neutrophil recovery of 17 days (range 10–42). All patients presented with 100% donor chimerism. One patient experimented secondary graft failure and died at D291 from infection and renal failure. During transplant procedure, 13 pts experimented at least one severe infectious complication (staphylococcus n=2; pseudomonas n=1; aspergillus n= 2; candida n=2; viral reactivation n= 13). 1 pt presented with moderate hepatic veno-occlusive disease. Five pts died from TRM and 12 pts remained alive in a good health condition. 36 month OS was 69% (95%CI 50 to 96). Cumulative incidence of grade 2 to 4 acute GVHD was 71% (95%CI: 41–87). 5 pts presented with either limited (n=4) or extensive (n=1) chronic GvHD and 36 month cumulative incidence of chronic GVHD was 33% (95%CI 11 to 58). To date, no pt had secondary malignancy. Discussion: Our study confirms the good results obtained by other groups when using flu-based RIC in FA pts. Indeed, satisfying engraftment and long-time survival rates were obtained without any TBI, irrespective of the stem cell source and the donor type. However, we have a concern regarding the cGVHD rate we obtained. As demonstrated by an on-going study of EBMT registry, the risk of secondary malignancy in these pts is statistically correlated to cGvHD. Then, this rate still remains probably too high in our study, even though only one pt presented with extensive cGvHD and no pts developed any secondary malignancy. But this could be explained by the short follow-up. Suppression of one alkalyting agent may reduce both cGVHD incidence and other tissue injuries leading to secondary malignancies. Then, we claim for suppression of Bu for related donor HSCT. In FA pts receiving transplant from unrelated donor, the relative impact of either low-dose IV-Bu – as we used here - or low-dose irradiation on toxicity and especially development of secondary malignancies remains to be evaluated. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Low Transplant Mortality in Allogeneic Bone Marrow Transplantation for Acute Myeloid Leukemia: A Randomized Study of Low-Dose Cyclosporin Versus Low-Dose Cyclosporin and Low-Dose Methotrexate

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3503-3508 ◽  
Author(s):  
P. Zikos ◽  
M.T. Van Lint ◽  
F. Frassoni ◽  
T. Lamparelli ◽  
F. Gualandi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Conditioning Regimen ◽  
Allogeneic Bone ◽  
End Points ◽  
Dose Methotrexate ◽  
Actuarial Risk ◽  
Acute Myeloid

Abstract Sixty patients undergoing allogeneic bone marrow transplant for acute myeloid leukemia (AML) in first remission (CR1; n = 49) or more advanced phase (n = 11) were entered in a prospective trial of graft-versus-host disease (GvHD) prophylaxis: low-dose cyclosporin A (IdCSA; 1 mg/kg/d from day −1 to +20 day; n = 28) or IdCSA plus low-dose methotrexate (IdMTX; 10 mg/m2 for day +1, 8 mg/m2 for days +3, +6, and +11; n = 32). Primary end points were acute GvHD (aGvHD) and transplant-related mortality (TRM); secondary end points were relapse and survival. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and fractionated total body irradiation (3.3 Gy/d for 3 consecutive days). The actuarial risk of developing aGvHD grade II-III was 61% for IdCSA alone and 34% for IdCSA + IdMTX (P = .02). The actuarial risk of TRM at 1 year was 11% versus 13%, respectively, and older patients (≧29 years) had higher TRM than younger patients (22% v 5%,P = .01). The age effect was significant in the IdCSA group (P = .04) but not in the IdCSA + IdMTX group (P = .1). The median follow-up is 4.4 years, with an overall actuarial survival of 78% for CR1 patients and 36% for patients with advanced disease. For patients in CR1 the outcome of the two regimens was as follows: survival 77% versus 80% (P = .6), relapse 20% versus 9% (P = .1), and TRM 13% versus 17% (P = .6). This study suggests that TRM can be reduced in AML patients undergoing allogeneic marrow transplants with a mild conditioning regimen and low-dose immunosuppression, and this translates in a 78% 5-year survival for CR1 patients. Beyond CR1 the major obstacle remains leukemia relapse, which is not prevented by low-dose in vivo immunosuppression.

A Randomized Trial of Rabbit Anti-Thymocyte Globulin, Given on Day+7 after Alternative Donor Transplants.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 754-754 ◽  
Author(s):  
Andrea Bacigalupo ◽  
Teresa Lamparelli ◽  
Fabio Ciceri ◽  
Fedro Peccatori ◽  
Anna Locasciulli ◽  
...  
Keyword(s):  
High Risk ◽  
Randomized Trial ◽  
Risk Score ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hemopoietic Stem Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Cox Analysis ◽  
To Receive

Abstract Background. We have shown that the risk of transplant mortality (TRM) can be predicted by using laboratory values, on day+7 after an allogeneic hemopoietic stem cell transplant (HSCT) (Sormani et al, Bone Marrow Transpl.2003). TRM in patients with low, intermediate and high risk on day+7, is 15%, 40% and 69%: increased mortality is mainly, but not exclusively, due to increased acute graft versus host disease (GvHD). In a pilot study we have shown that a small dose of rabbit anti-thymocyte globulin (rATG) (Thymoglobulin, Genzyme), was feasible and reduced GvHD and TRM. Aim of the study. We have therefore opened a randomized trial testing this hypothesis in patient undergoing an unrelated donor HSCT, with rATG (7.5 mg/kg) in the conditioning regimen. Patients. 170 were eligible: all patients received rATG 3.75 mg/kg x2 pre-transplant, and on day+7 they were scored and randomized to receive an additional dose of rATG (1,25 mg/kg day +7 and day+9) (n=84) or to receive no further treatment (n=86) (control arm). The two groups were balanced for age, disease phase and day+7 score. Results. The predictive value of day+7 score on TRM was confirmed in the control arm (18% vs 42% for intermediate and high risk patients, p=0.03), whereas in the day+7 ATG arm, there was no difference (29% vs 29%, p=1.0). TRM was overall reduced from 35% in the control arm to 29% in the ATG day+7 arm (p=0.37) : the difference was more pronounced in patients with early disease and high risk on day 7 (35% vs 15% p=0.08). Acute GvHD grade III–IV was reduced overall from 16% to 6% (p=0.04), and chronic GvHD was reduced 32% to 14% (p=0.02). In multivariate COX analysis TRM and overall survival was predicted by risk score day7 and disease phase. Conclusions. We confirm that patients with different risk of TRM can be identified on day+7 after HSCT. Administration of rATG on day+7 can influence the risk of TRM, by reducing acute and chronic GvHD. Additional intensified supportive care (including anti-infectious therapy) may further reduce TRM in patients with a high risk score on day+7.

Haematopoietic Stem Cell Transplantation: A Single Centre Experience from Army Hospital (Research & Referral), New Delhi, India

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4377-4377
Author(s):  
Velu Nair ◽  
Ajay Sharma ◽  
Satyaranjan Das ◽  
Deepak Kumar Mishra ◽  
Jyoti Kotwal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Chronic Gvhd ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Overall Mortality

Abstract Haematopoietic stem cell transplantation {HSCT} is being offered as a definitive mode of therapy in various hematological disorders. We present retrospective data of 113(39 females) patients who underwent HSCT in High Efficiency Particulate Air {HEPA} filtered unit. Of these, 36 underwent Autologous HSCT {Auto-HSCT} comprising of 15 patients for Acute Myeloid Leukemia {AML} and 21 for Multiple Myeloma{MM}.). The indications for Allogenic HSCT {Allo-HSCT} were Chronic Myeloid Leukemia{CML}-19;AML-17; Thalassaemia Major-18;Myelodysplastic Syndrome{MDS}-01; Acute Lymphoblastic Leukemia-09,; Severe Aplastic Anemia {SAA}-09; Pure red cell Aplasia-02 and Juvenile Myelomonocytic Leukemia-02. All allogeneic recipients, received stem cells from HLA matched siblings. The conditioning was done with standard busulfan-cyclophosphamide (Bu-Cy) based protocols for leukemia; fludarabine, cyclophosphamide & Anti-Thymocyte globulin {ATG} for SAA; Bu-Cy-ATG for thalassemia and melphalan for MM. The mean age was 25 years (2–60). The median cell dose was 6.0×108MNC/Kg (2.2–11.7). The median day of engraftment for neutrophils (ANC > 500/mm3) was on day 11(7–22) and for platelets (Plt >20,000/mm3) it was on day 13(8–37). Peripheral blood was used as a source of stem cells for all patients who underwent Auto-HSCT, except for two patients where bone marrow was also harvested in addition, to achieve adequate cell dose. For Allo-HSCT, peripheral blood was used for 47 patients and bone marrow for 29 patients. Both bone marrow and cord blood was used in one patient for Allo-HSCT. Analysis of All-HSCT: Analysis revealed 13/77(16.88%) patients developed sinusoidal obstruction syndrome {SOS}. Of these 06 had severe SOS and 04 of them died. 5/77(6.49%) patients developed hemorrhagic cystitis who responded to conservative management. Incidence of grade III/IV acute graft versus host disease {GVHD} was 10/77 (12.98%), of which 4 patients died. Of these, 3 were Thalassemia Major patients who underwent bone marrow stem cell transplant {BMSCT} while the remaining were hematological malignancies (CML-04; AML-01; ALL-02) who underwent peripheral blood stem cell transplant {PBSCT}. Also, 20/77 (25.97%) patients were noted to have chronic GVHD (Limited-12 & Extensive-08). Interestingly there was strikingly higher incidence of chronic GVHD in the PBSCT group i.e. 19/47 (40.43%) as compared to BMSCT group where it was only 1/30 (3.34%). This was found to be statistically significant (p<0.05). The overall mortality in Allo-HSCT group was 27/77 (35.07%) which included 10 deaths due to relapse of the underlying disease. Transplant related mortality (TRM) was 17/77(22.08%). In the TRM group, 11 were PBSCT while 6 were BMSCT. TRM <100 days comprised of 13/77 (16.88%) patients and causes of death were sepsis (06); severe VOD (04) and acute GVHD (03). Overall survival was 50/77 (64.94%) with a median follow up of 450 days (90–2329). Analysis for Auto-HSCT: Only two i.e. 2/36 (5.56%) patients developed mild SOS. Overall mortality in this subset was 6/36 (16.67%). This included only one TRM i.e. 1/36 (2.78%) and 05 deaths due to relapse of the disease (AML-3 & MM-2). Two patients have died due to unrelated causes (one due to heat stroke and one due to head injury). Two patients have been lost to follow up. Overall survival was 26/34(76.47%) with a median follow up of 579 days (90–2414).

scholarly journals Impact of Different Doses of Fludarabine in Fludarabine-Based Conditioning Regimen for Unrelated Bone Marrow Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3258-3258
Author(s):  
Kodai Kuriyama ◽  
Shigeo Fuji ◽  
Noriko Doki ◽  
Yuta Katayama ◽  
Souichi Shiratori ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
High Dose ◽  
The Impact

Background: The purine analog fludarabine (Flu) is recognized as an agent having strong immunosuppressive effects and plays a central role in reduced-intensity conditioning (RIC) and myeloablative reduced-toxicity conditioning (RTC) regimens because of limited nonhematologic toxicities. Combinations of Flu and busulfan (Bu) (FB group) or melphalan (Mel) (FM group) are the commonly used as RIC and RTC regimens. Flu inhibits lymphocyte proliferation, induces apoptosis of hematologic malignant cells and has a synergistic tumor-killing effect with alkylating agents such as Bu and Mel. Few reports assess the impact of different dose of Flu on the clinical outcome. In this study, to compare the impact of Flu doses in RIC or RTC, we retrospectively analyzed clinical outcomes in patients who received FB or FM conditioning by using nationwide registration data of Japan Society for Hematopoietic Cell Transplantation. Method: Patients aged 16 years of older with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia and malignant lymphoma, who received FB or FM conditioning regimen, and who underwent bone marrow transplantation from an unrelated donor between 2007 and 2016 were included in this study. We excluded patients who received oral Bu. Also, patients who had renal dysfunction in Hematopoietic Cell Transplantation-Comorbidity Index was excluded because Flu dose needs an adjustment due to renal function. As a result, 2809 patients were included in this study. All transplantation data in the present study were obtained from the Transplant Registry Unified Management Program (TRUMP), which included clinical data of hematopoietic cell transplantation performed in Japan. Result: In the FB group (n=1647), high-dose Flu (180 mg/m2; HFB) and low-dose Flu (150/125 mg/m2; LFB) were used in 1334 and 313 patients, respectively. The probabilities of 3-year OS and PFS in the HFB group were significantly higher than that in the LFB group (49% vs 38%, P<0.001; 44% vs 35%, P=0.007). The cumulative incidences of relapse at 3 years were 30.4% and 36.6% (P=0.058), and NRM at 3 years were 25.1% and 28.1% (P=0.24) in the HFB and LFB groups, respectively. In multivariate analysis for OS and relapse, Flu doses was identified as an independent prognostic factor (HR 0.82, P=0.03; HR 0.8, P=0.043). In the FM group (n=1162), high-dose Flu (180 mg/m2; HFM) and low-dose Flu (150/125 mg/m2; LFM) were used in 118 and 1044 patients, respectively. There was no significant difference in the OS, relapse and NRM rates between HFM and LFM (at 3 years, 51.4% vs 48.5%, P=0.596; 22.4% vs 27.0%, P=0.362; 30.7% vs 30.3%, P=0.783). Conclusion: In this large study, we suggested that high-dose Flu was associated with favorable outcome in the FB group, but not in the FM group. Prospective studies and further investigations are needed to clarify the benefit of high-dose Flu in the setting of FB regimen. Disclosures Ozawa: Kyowa-Hakko Kirin: Honoraria; Astellas Pharma Inc.: Honoraria; Pfizer Japan Inc.: Honoraria; Novartis: Honoraria. Kanda:Daiichi Sankyo Company: Honoraria; Bristol-Meyers Squib: Honoraria; Celgene: Honoraria; MSD: Honoraria; JCR Pharmaceuticals: Honoraria; Takeda: Honoraria; Otsuka: Honoraria; Kyowa Hakko Kirin: Honoraria; Chugai: Honoraria; Astellas: Honoraria; Novartis: Honoraria; NextGeM Incorporation: Patents & Royalties: 2019-011392. Atsuta:Kyowa Kirin Co., Ltd: Honoraria; CHUGAI PHARMACEUTICAL CO., LTD.: Honoraria.

scholarly journals Low Transplant Mortality in Allogeneic Bone Marrow Transplantation for Acute Myeloid Leukemia: A Randomized Study of Low-Dose Cyclosporin Versus Low-Dose Cyclosporin and Low-Dose Methotrexate

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3503-3508
Author(s):  
P. Zikos ◽  
M.T. Van Lint ◽  
F. Frassoni ◽  
T. Lamparelli ◽  
F. Gualandi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Conditioning Regimen ◽  
Allogeneic Bone ◽  
End Points ◽  
Dose Methotrexate ◽  
Actuarial Risk ◽  
Acute Myeloid

Sixty patients undergoing allogeneic bone marrow transplant for acute myeloid leukemia (AML) in first remission (CR1; n = 49) or more advanced phase (n = 11) were entered in a prospective trial of graft-versus-host disease (GvHD) prophylaxis: low-dose cyclosporin A (IdCSA; 1 mg/kg/d from day −1 to +20 day; n = 28) or IdCSA plus low-dose methotrexate (IdMTX; 10 mg/m2 for day +1, 8 mg/m2 for days +3, +6, and +11; n = 32). Primary end points were acute GvHD (aGvHD) and transplant-related mortality (TRM); secondary end points were relapse and survival. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and fractionated total body irradiation (3.3 Gy/d for 3 consecutive days). The actuarial risk of developing aGvHD grade II-III was 61% for IdCSA alone and 34% for IdCSA + IdMTX (P = .02). The actuarial risk of TRM at 1 year was 11% versus 13%, respectively, and older patients (≧29 years) had higher TRM than younger patients (22% v 5%,P = .01). The age effect was significant in the IdCSA group (P = .04) but not in the IdCSA + IdMTX group (P = .1). The median follow-up is 4.4 years, with an overall actuarial survival of 78% for CR1 patients and 36% for patients with advanced disease. For patients in CR1 the outcome of the two regimens was as follows: survival 77% versus 80% (P = .6), relapse 20% versus 9% (P = .1), and TRM 13% versus 17% (P = .6). This study suggests that TRM can be reduced in AML patients undergoing allogeneic marrow transplants with a mild conditioning regimen and low-dose immunosuppression, and this translates in a 78% 5-year survival for CR1 patients. Beyond CR1 the major obstacle remains leukemia relapse, which is not prevented by low-dose in vivo immunosuppression.

scholarly journals A review of current knowledge of myeloproliferative disorders in the horse

2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Katy Satué ◽  
Juan Carlos Gardon ◽  
Ana Muñoz
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Current Knowledge ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Disorders ◽  
World Health ◽  
Chronic Granulocytic Leukemia ◽  
Current State ◽  
Multiple Cell ◽  
Health Organization

AbstractMyeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.

scholarly journals Immunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Changes

2021 ◽  
Vol 20 ◽  
pp. 153473542110026
Author(s):  
Andrana K. Calgarotto ◽  
Ana L. Longhini ◽  
Fernando V. Pericole de Souza ◽  
Adriana S. Santos Duarte ◽  
Karla P. Ferro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Green Tea ◽  
Regulatory T Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Related Factor ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Green tea (GT) treatment was evaluated for its effect on the immune and antineoplastic response of elderly acute myeloid leukemia patients with myelodysplasia-related changes (AML-MRC) who are ineligible for aggressive chemotherapy and bone marrow transplants. The eligible patients enrolled in the study (n = 10) received oral doses of GT extract (1000 mg/day) alone or combined with low-dose cytarabine chemotherapy for at least 6 months and/or until progression. Bone marrow (BM) and peripheral blood (PB) were evaluated monthly. Median survival was increased as compared to the control cohort, though not statistically different. Interestingly, improvements in the immunological profile of patients were found. After 30 days, an activated and cytotoxic phenotype was detected: GT increased total and naïve/effector CD8+ T cells, perforin+/granzyme B+ natural killer cells, monocytes, and classical monocytes with increased reactive oxygen species (ROS) production. A reduction in the immunosuppressive profile was also observed: GT reduced TGF-β and IL-4 expression, and decreased regulatory T cell and CXCR4+ regulatory T cell frequencies. ROS levels and CXCR4 expression were reduced in bone marrow CD34+ cells, as well as nuclear factor erythroid 2–related factor 2 (NRF2) and hypoxia-inducible factor 1α (HIF-1α) expression in biopsies. Immune modulation induced by GT appears to occur, regardless of tumor burden, as soon as 30 days after intake and is maintained for up to 180 days, even in the presence of low-dose chemotherapy. This pilot study highlights that GT extracts are safe and could improve the immune system of elderly AML-MRC patients.

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