High Engraftment Rate after Second Stem Cell Transplantation for Thalassemia: A Prospective Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1107-1107
Author(s):  
Javid Gaziev ◽  
Guido Lucarelli ◽  
Pietro Sodani ◽  
Paola Polchi ◽  
Katia Paciaroni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Second Transplantation ◽  
Increased Risk ◽  
Preparative Regimen

Abstract Unlike hematological malignancies patients with thalassemia have an increased risk of graft failure or rejection occurring in up to 15% of patients after myeloablative stem cell transplantation from HLA identical related donors. Patients who reject their grafts and have a return of thalassemic hematopoiesis could benefit from second transplantation with the prospect of cure. Our previous experiences of second SCT using BUCY conditioning regimen alone or in combination with antilymphocyte globulin or total lymphoid irradiation showed a higher graft failure rates (43% to 69%). In 2003 we devised a new preparative regimen in an attempt to improve engraftment rate after second transplantation for thalassemia. The treatment protocol (Protocol 26.1) consisted of pre-conditioning immunosuppression-cytoreduction with hydroxiurea 30 mg/kg/day, azathioprine 3 mg/kg/day (day -45 to -12) and fludarabine 30 mg/m2/day (day -17 to -13) and conditioning regimen with BU 14/16 TT10 CY200 ATG (Thymoglobulin)12,5/10. Thirteen patients with median age of 9 years (range, 4–20 years) were given a second SCT according to this protocol. The median time between the first and second transplant was 29 months (range, 8–204 months). As a stem cell source 4 patients received bone marrow and 9 patients unmanipulated peripheral blood stem cells (PBSC). All but two patients received stem cells from the same donor. Twelve out of 13 patients (92%) had sustained full donor engraftment. One patient had early graft failure and died from cerebral bleeding due to refractory thrombocytopenia despite an autologous back-up. Other two patients died from acute or chronic GvHD -related complications. The probability of survival, thalassemia-free survival, transplant related mortality and rejection were 76%, 76%, 18% and 8% respectively with a median follow-up of 26 months (range, 8–47 months). Four patients developed grade II–III and 1 patient grade IV acute GvHD responsive to steroids and 3 patients had extensive chronic GvHD. Both acute and chronic GvHD occurred in patients who received PBSC. The incidence of CMV and EBV reactivation was 62% and 38% respectively. None of these patients developed EBV related lymphoproliferative disorders. Six patients had BK virus- related hemorragic cystitis (2 moderate, 2 severe and 2 mild cystitis). In conclusion, the high engraftment rate observed in this study suggests that this new preparative regimen is effective curative treatment for second transplant in patients with thalassemia. Disclosure: No relevant conflicts of interest to declare.

Impact of antithymocyte globulin (ATG)-containing conditioning regimens on patients undergoing allogeneic stem cell transplantation (allo-CST) for poor risk cytogenetic IPSS myelodysplastic syndrome (PRC-MDS): A report from the French Society of Stem Cell Transplantation and Cell  Therapy (SFGM-TC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6542-6542
Author(s):  
Ibrahim Yakoub-Agha ◽  
Gandhi Laurent Damaj ◽  
Marie Robin ◽  
Stephane Vigouroux ◽  
Alice Garnier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
French Society ◽  
Poor Risk ◽  
Increased Risk

6542 Background: Due to a risk of relapse of underlying disease in patients with PRC-MDS, the use of ATG, incorporated within the conditioning regimen prior to allo-SCT, is still controversial. Methods: Inclusion criteria included patients aged over 18 (n=101) who received allo-SCT transplanted between 1999 and 2009 from either a sibling (n=68) or HLA-allele-MUD (10/10) (n=33) for PRC-MDS. HLA matching was double-checked by the national Bone Marrow Donor Registry. Results: According to the FAB/WHO classification at diagnosis, 22 pts had RA/RARS/RCMD, 40 RAEB1, 30 REAB2 and 9 RAEB-t/AML. 34 pts had progressed to a more advanced disease before allo-SCT. At diagnosis, 89 patients had an IPSS int-2 or higher. At transplant, 36 pts were responders (CR, PR, CRm) and 62 with progressive disease (relapsed/refractory, untreated or stable disease without hematological improvement). Median age at transplantation was 54 years (range, 22-69). Pts received myeloablative conditioning (n=46) and nonmyeloablative (n=55). In this series, 48 patients received ATG as part of conditioning ('ATG' group), whereas 53 did not ('no-ATG’ group). As of April 1st 2011, 44 patients died of relapse and 22 of TRM. 3-year relapse, overall and event-free survival rates were not significantly different between the two groups. In contrast, the cumulative incidence of grade 2-4 acute GVHD was 48% in the no-ATG group and 30% ATG group (P <.005). Although the cumulative incidence of chronic GVHD was similar in the no-ATG and ATG groups, a trend for a lower TRM was observed in the ATG group (p=.06). In multivariate analysis, the absence of use of ATG was associated with an increased risk of acute grade 2-4 [HR = 1.92, p=.044]. Conclusions: The addition of ATG to the conditioning regimen resulted in a decreased incidence of acute GVHD without increasing relapse rates and compromising survival of patients undergoing allo-SCT for poor risk cytogenetic MDS.

scholarly journals HLA-Haploidentical Donors Seem to be Not Inferior to HLA-Identical Sibling Donors for Hematopoietic Stem Cell Transplantation of Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5867-5867
Author(s):  
Feng Chen ◽  
Depei Wu ◽  
XiaoWen Tang ◽  
Miao Miao ◽  
Chengcheng Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Short Term ◽  
Hematopoietic Stem ◽  
Alternative Option

Abstract Background PNH is an acquired clonal disorder of the hemopoietic stem cells for which the only curative treatment is allogeneic hematopietic stem cell transplantation (allo-HSCT). But allo-HSCT is challenging for those who have no HLA-matched donors.Several recent studies have shown that haploidentical HSCT for patients with hematological malignancy can achieved comparable outcomes with HLA-identical sibling transplantation . There are very few reports on the use of haploidentical HSCT for PNH . Is haploidentical HSCT a valid alternative option for patients with PNH? Methods 19 PNH patients received allo-HSCT between Dec 2007 and Oct 2015 at our institution. 12 donors were HLA-haploidentical and 7 were HLA-matched siblings. The patients were aged 8 to 54 years (median 28 years) . Of the 12 haploidentical donors, 6 were siblings, 2 fathers,2 mothers,1 son and 1 daughter. 12 patients with haploidentical donors received a myeloablative conditioning regimen consisting of busulfan, cyclophosphamide and ATG (anti-thymocyte globulin), 7 patients with identical siblings were given a reduced intensity conditioning. G-CSF-mobilized bone marrow and peripheral blood stem cells were transplanted as graft. Prophylaxis for graft-versus-host disease (GVHD) consisting of cyclosporine or tacrolimus + short-term methotrexate + mycophenolate mofetil was used for 12 patients with haploidentical donors, and cyclosporine + short-term methotrexate for 7 with identical siblings. Results All 19 patients were engrafted successfully. The median time of neutrophils (ANC) reached to 0.5×109/L and platelets (PLT) reached to 20×109/L was 12 days and 15 days in haploidentical group , and that to identical group was 11 days and 13 days ,respectively. There were 2 patients developed grade Ⅱ acute GVHD in haploidentical group while 1 patients with grade Ⅳ aGVHD in identical group . Limited chronic GVHD was observed in 2/12 patients in haploidentical group and 1/7 patients in identical group. After a median follow-up time of 22.0 (range 4.0-42.0) months, the 3-year OS probability was 77.8±13.9% and 85.7±13.2% for haploidentical and identical group,respectively (P=0.03). 2 patients died of treatment-related mortality in haploidentical group, including severe pulmonary infection (n=1) and transplant-associated thrombotic microangiopathy (n=1) ,and 1 died of severe aGVHD in identical group. No patients were documented to have a recurrence of a PNH clone after HSCT in both groups. Conclusion This report seemed that long-term outcomes of HLA- haploidentical HSCT in patients with PNH were comparable to that of HLA- matched donor at our institution . Haploidentical HSCT should be considered as a valid alternative option for PNH patients without HLA- matched donors . Disclosures No relevant conflicts of interest to declare.

Durable Engraftment with Minimal Toxicities after Allogeneic Hematopoietic Stem Cell Transplantation with a Reduced-Intensity Regimen Incorporating Fludarabine and 8 mg/kg Busulfan.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5246-5246
Author(s):  
Naoyuki Uchida ◽  
Takahiro Fukuda ◽  
Atsushi Wake ◽  
Sung-Won Kim ◽  
Kazuhiro Masuoka ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Reduced Intensity

Abstract Background: The optimal regimen for allogeneic stem cell transplantation with a reduced-intensity conditioning regimen (RIST) needs to be established. Therefore, we retrospectively reviewed data of 84 patients who underwent RIST using 180 mg/sqm fludarabine and 8 mg/kg busulfan (Flu/Bu8). All patients received mobilized blood stem cells from a related donor between Nov. 2000 and Jun. 2005. Patients and Methods: The median age of the patients was 53 years (range, 25–65). The diagnosis included 42 AML/MDS, 34 lymphoma and 8 others. Sixty-nine patients (82%) had high-risk diseases, including 56 (81%) in non-remission status before RIST. All were serologically 6/6 matched pairs, except for one who had a 5/6 match. For GVHD prophylaxis, 61 used cyclosporine A (CSP) alone, 21 used CSP + methotrexate (MTX), and 2 used some other compounds. Results: The engraftment kinetics were remarkable since all of the patients successfully engrafted at a median of 11 days (5–24 days), with no late graft rejection. Toxicities of grade 2 or 3 according to CTCAE v.3 were observed at minimal frequencies, i.e. 38 mucosal, 35 hepatic, 13 GI tract, 12 renal, 2 cardiac, 1 pulmonary, 19 febrile neutropenia, and 9 documented infections, and there were no grade 4 toxicities. The administration of MTX increased the incidence and severity of stomatitis (P=0.05). The cumulative incidences of grade II–IV and III–IV acute GVHD were, respectively, 50% and 29%, and 76% experienced chronic GVHD. Seventy-three patients (87%), including 38 of the 56 patients who were not in CR at the time of transplant, achieved partial or complete remission. The median follow-up of surviving patients was 1349 days (34–1981 days), and the day-100 mortality was 11% (disease progression 6% and non-relapse mortality [NRM] 5%). The 5-year overall and progression-free survival rates were 36% and 30%, respectively. Among 46 total deaths, 27 were from disease progression and 19 were from NRM primarily related to GVHD. The patients in remission at transplant showed better overall survival than those who were not in remission (85 % vs 34 % at 5 years post-transplant, respectively, P<0.05). The 5-year overall survival was 85 % for those in remission at transplant and 34 % for the remaining patients (P<0.05). Multivariate analyses showed that age older than 52 years and non-CR status at transplant were associated with an increased risk for mortality after RIST. Conclusions: Our study showed that RIST with this Flu/Bu8 regimen is feasible with durable engraftment and low early mortality. The clinical response rate is adequate for those who stayed in remission at transplantation, but otherwise a novel approach to prevent disease progression should be developed.

Impact of T-Cell Chimerism on Clinical Outcome in 117 Patients Who Underwent Allogeneic Stem Cell Transplantation with a Busulfan-Containing Reduced-Intensity Conditioning Regimen.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2009-2009
Author(s):  
Bungo Saito ◽  
Takahiro Fukuda ◽  
Hiroki Yokoyama ◽  
Saiko Kurosawa ◽  
Toshihiro Takahashi ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Increased Risk ◽  
Wide Range ◽  
The Mean ◽  
Reduced Intensity

Abstract Background: Within the concept of reduced-intensity stem cell transplantation (RIST), there is a wide range of differences in regimens utilized, in terms of toxicities and antileukemia effects, and only a little information is available on the clinical impact of chimerism status in patients conditioned with a busulfan-containing regimen. To examine this point, we reviewed the pattern of lineage-specific chimerism to correlate with subsequent clinical outcomes. Patients and Methods: We retrospectively reviewed the data of 117 patients (median age, 52 years: range, 29–68) who had various hematological malignancies and underwent busulfan-containing RIST with related blood stem cells (n=81), related marrow (n=4) or unrelated marrow (n=32), between January 2000 and December 2006. The conditioning regimen consisted of busulfan (8 mg/kg) and fludarabine (180 mg/m2, n=64) or cladribine (0.66 mg/kg, n=53), with or without 2–4 Gy TBI (n=26) or anti-thymocyte globulin (5–10 mg/kg: n=31). Prophylaxis for GVHD consisted of cyclosporin or tacrolimus, with or without methotrexate. Chimerism was evaluated with peripheral blood samples taken on days 30, 60 and 90 after transplantation by PCR-based amplification of polymorphic short tandem repeat regions. Results: The median follow-up of surviving patients was 857 days (50–2535). Percent donor-chimerism was significantly higher in granulocytes than T-cell fraction throughout the entire course, and the mean values were, respectively, 96% vs 83%, 98% vs 89% and 98% vs 91% at days 30, 60 and 90 after RIST. At day 30, the numbers of patients with T-cell chimerism &gt;90%, 60–90% and &lt;60% were 67 (58%), 32 (27%) and 18 (15%), respectively. The mean percentage of donor T-cell chimerism on day 30 was 18% (0–63%) in 5 patients who experienced graft failure (GF), which was significantly lower than that (86%; 15–100%) in the rest of the patients (p&lt;0.01). No correlation was found between the kinetics of T-cell chimerism and the occurrence of acute or chronic GVHD. A multivariate analysis showed that low donor T-cell chimerism of &lt;60% at day 30 was significantly associated with an increased risk of treatment failure (TF) at day 100, which included GF, progressive disease, relapse and non-relapse mortality (HR: 3.3 [95% CI, 1.4–7.8] p&lt;0.01), but not with 1-year TF. The stem cell source and the addition of TBI or ATG were not associated with the degree of T-cell chimerism, overall survival (OS) or TF. In a Cox proportional hazard model, low donor T-cell chimerism of &lt;60% at day 30 was associated with poor OS (HR: 2.2 [95% CI, 1.1–4.4] p=0.02) (Figure) and TF (HR: 2.0 [95% CI, 1.1–3.8] p=0.02). Conclusion: We found that 42% of the patients retained mixed donor T-cell chimerism (≤90% donor), whereas 92% achieved complete chimerism in granulocyte fraction. Low donor T-cell chimerism of &lt;60% at day 30 may predict a poor outcome, and a prospective study to examine the value of early intervention based on chimerism data is warranted. Figure Figure

HLA-Matched Sibling Stem Cell Transplantation Using Conditioning Regimen with Reduced Dose of Cyclophosphamide, ATG and Fludarabine in Patients with Severe Aplastic Anemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3296-3296
Author(s):  
Jong Wook Lee ◽  
Byung Sik Cho ◽  
Yoo Jin Kim ◽  
Seok Lee ◽  
Hee Je Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Cell Transplantation ◽  
Graft Failure ◽  
Cardiac Toxicity ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Dose ◽  
Matched Sibling

Abstract Background: We have reported the outcome of HLA-matched stem cell transplantation (SCT) using triple immunosuppressive agents with cyclophosphamide (CY, 200mg/kg), ATG and procarbazine for 113 adult patients with severe aplastic anemia (SAA) (Kim et al, BMT31:79, 2003). However, high dose CY (200mg/kg) causes serious cardiac toxicity in some cases which may lead to death within few weeks. To avoid high dose CY-associated cardiac toxicity we underwent HLA-matched sibling SCT using increasing dose of ATG and Fludarabine instead of reduced CY to half dose. Method: Between March 2002 and December 2007, fifty patients with adult SAA (six patients were AA/PNH syndrome) received matched sibling SCT. The median age of patients was 39 (16~53) and median interval between Dx and SCT was 19 months (1~352). The median number of transfusion prior to SCT was 34 units (2~680). Nineteen patients (38%) had a history of IST before SCT. The conditioning regimen consisted of Fludarabine (30mg/m2/day, 6 days), CY (50 mg/kg/day, 2 days) and ATG (Thymoglobulin 2.5mg/kg/day, 4 days). Stem cell sources were BM plus CD34+-selected PBSC (n=12), BM (n=20), PBSC (n=4) and G-CSF-primed BM (n=14). All patients received cyclosporine and methotrexate as GVHD prophylaxis. Results: The median dose of CD34+ cells infused was 3.7x106/kg (1.2~11.9). All patients achieved successful primary engraftment, and the median time for ANC and platelet to reach 0.5x109/L and 20x109/L was 12 (10~19) and 17 (10~25) days, respectively. Three patients (6%) developed delayed graft failure whereas 14% (16 out of 113) developed both primary and secondary graft failure in our previous study. But all achieved successful engraftment after booster infusion (n=1) and second SCT (n=2). The incidence of acute GVHD (more than grade II) and chronic GVHD was 8% (n=4) and 4% (n=2; extensive type), respectively. The incidence of acute and chronic GVHD seems to be lower than those of previous conditioning regimen (11% and 12%, respectively) (BMT31:79, 2003). The incidence of CMV infection requiring preemptive treatment was 54 % (n=27). Three patients died of reactivation of chronic hepatitis C with hepatic GVHD (n=1), CMV pneumonia (n=1), and invasive fungal infection (n=1). PNH clone monitored by flow cytometry disappeared posttransplant in all 6 PNH patients. With median follow up of 32 months (1~74), the estimated probability of survival at 3 years was 94 % compared with those of 89% in our previous report. Conclusions: These data demonstrate that the conditioning regimen used in this study is feasible for patients with SAA who received matched sibling SCT. Of note, the observation of successful engraftment as well as lesser acute and chronic GVHD compared with previous study suggest that increasing dose of ATG and the addition of Fludarabine has potent in vivo T cell depletion and immunomodulatory activity.

Haploidentical Stem Cell Transplantation for Patients Relapsing after First Allogeneic Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4618-4618
Author(s):  
Virginie Lavoipierre ◽  
Samia Harbi ◽  
Luca Castagna ◽  
Angela Granata ◽  
Sabine Fürst ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Good Survival ◽  
Hematopoietic Stem ◽  
Second Transplantation

Abstract INTRODUCTION: Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains a major therapeutic challenge: outcome is very poor, without curative option in most cases. Second alloHSCT may be considered in few selected patients because of anticipated limitations: 1) donor availability; 2) high toxicity due to previous treatments; 3) low efficacy considering the very advanced disease situation. We hypothesized that the use of post transplantation Cyclophosphamide (pCY) haplo-SCT may be an interesting alternative to overcome these limitations. In particular, the presence of full haplotype HLA mismatch could provide a decisive antileukemic effect relative to alloreactivity. In absence of large series in this setting, we report here the outcome after HaploSCT for patients who relapse after a first alloHSCT. METHODS: We retrospectively studied adult patients, who received a second pCy Haplo-SCT for hematological malignancies. Patients were treated between 2009 and 2016. The objective was to assess both the feasibility and the efficacy of HaploSCT in this setting. RESULTS: Twenty seven patients were included: median time between first alloHSCT and relapse was 11 months (range: 1-82). Median age at second transplantation was 49 years old (range: 21-61). Most of patients had acute myeloid leukemia (n=12, 44%) or Hodgkin lymphoma (n=6 patients, 22%). Fifteen patients (55%) were in complete remission at the time of pCY Haplo-SCT. Hematopoietic cell transplantation-comorbidity index was ≥ 3 in 20 patients (74%). Thirteen patients (48 %) received non-myeloablative conditioning regimen (as Baltimore schema, Luznik et al. BBMT 2008) prior to HaploSCT while remaining patients received busulfan-based regimen. Day+100 cumulative incidence of grade 2 to 4 and 3 to 4 acute GVHD was 15% and 7%. 2-year cumulative incidence of chronic GVHD was 12%. The cumulative incidence of non-relapse mortality and relapse at 2 years were 38% and 27%, respectively. With a median follow up of 25 months (range: 4-63), 2-year progression-free and overall survivals were 36% and 39%, respectively. Disease status at the time of HaploSCT was a major determinant for outcome. Indeed, 2-year NRM and OS were 58% and 25% in patients transplanted with active disease, respectively, while corresponding values in patients transplanted in CR were 21% (p=0.036) and 49% (p=0.041), respectively (Figure 1A and 1B). CONCLUSION: We can conclude that in selected patients who could be candidate for second transplantation, HaploSCT is feasible and may represent a curative option. The overall incidence of relapse of 27% is promising in this situation for which no alternative for cure is available, with relatively good survival in patients transplanted in CR. However, the very high NRM (58%) in refractory patients should make us consider second transplant with caution in this setting. For these patients, specific developments are needed to avoid procedure-related toxicity. Disclosures No relevant conflicts of interest to declare.

Haematopoietic stem cell transplantation

2015 ◽  
Author(s):  
Drew Provan ◽  
Trevor Baglin ◽  
Inderjeet Dokal ◽  
Johannes de Vos ◽  
Hassan Al-Sader
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Haematopoietic Stem Cell ◽  
Sinusoidal Obstruction Syndrome ◽  
Cell Transplant ◽  
Post Transplant

Haemopoietic stem cell transplantation (SCT) - Indications for haemopoietic SCT - Allogeneic SCT - Autologous STC - Investigations for BMT/PBSCT - Pretransplant investigation of donors - Bone marrow harvesting - Peripheral blood stem cell mobilization and harvesting - Microbiological screening for stem cell cryopreservation - Stem cell transplant conditioning regimens - Infusion of cryopreserved stem cells - Infusion of fresh non-cryopreserved stem cells - Blood product support for SCT - Graft-versus-host disease (GvHD) prophylaxis - Acute GvHD - Chronic GvHD - Veno-occlusive disease (syn. sinusoidal obstruction syndrome) - Invasive fungal infections and antifungal therapy - CMV prophylaxis and treatment - Post-transplant vaccination programme and foreign travel - Longer term effect post-transplant - Treatment of relapse post-allogeneic SCT - Discharge and follow-up

Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan

Blood ◽  
2012 ◽  
Vol 120 (2) ◽  
pp. 473-476 ◽  
Author(s):  
Maria Ester Bernardo ◽  
Eugenia Piras ◽  
Adriana Vacca ◽  
Giovanna Giorgiani ◽  
Marco Zecca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Hematopoietic Stem

Abstract Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.

Myeloablative Treosulfan as Preparative Regimen for Allogeneic Haematopoietic Stem Cell Transplantation: A Single-Centre Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3343-3343
Author(s):  
Rudolf Trenschel ◽  
Markus Ditschkowski ◽  
Ahmet Elmaagacli ◽  
Nina K. Steckel ◽  
Michal Hlinka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Advanced Disease ◽  
Chronic Gvhd ◽  
Water Soluble ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Early Disease ◽  
Increased Risk

Abstract Treosulfan (TREO), a water-soluble bifunctional alkylating agent, has demonstrated strong immunosuppressive and antileukemic activity as well as profound stem cell toxicity in animal studies. Due to the advantageous clinical toxicity profile lacking significant non-hematologic organ toxicities, high-dose TREO in combination with cyclophosphamide (CY) has recently been evaluated in patients (pts) with an increased risk for organ toxicities precluding standard myeloablative conditioning regimens before allogeneic stem cell transplantation (SCT). Between 8/00 and 10/03, we treated 52 patients (pts) not eligible for conventional therapy with TREO in order to reduce toxicity in a myeloablative setting. Diagnoses were AML (n=14), ALL (n=11), MM (n=8), NHL (n=7), MDS (n=5), CML (n=4) and aplastic syndromes (n=3). 18 patients were grafted in early disease (1st or 2nd complete remission, chronic phase, or incipient first relapse (BM blasts < 10%). The remaining pts were classified as having advanced disease. Donors were identical siblings (n=24), non-identical family members (n=l), matched unrelated (n=14) or mismatched unrelated (n=13) donors. Conditioning regimen consisted of TREO 36g/qm (n=19) or 42g/qm (n=28) and CY 120mg/kg BW, 5 pts received TREO 42g/qm and fludarabine 150mg/qm. GvHD prophylaxis consisted of CSA alone (n=l) or in combination with short course MTX (n=25), alemtuzumab (n=22) or ATG (n=4). ANC > 500/μl and platelets > 20000/μl were reached at day 15 and 16 respectively. Acute GvHD grade II - IV occurred in 31% of pts and chronic GvHD in 60% of pts. Overall (OS) and disease free survival (DFS) were closely related to disease status. OS and DFS was 93% and 82,9% after a median of 18 months (range 0,9–38,5 months) for pts with early disease. In advanced disease the OS was 57,4% and the DFS 47,9% after a median of 4,8 months (range 0,3 – 22,9 months), respectively. In early disease, a single patient died of invasive aspergillosis associated with grade IV aGvHD. Another patient developed a relapse of CML which was successfully treated with DLI. Clinical relevant adverse events occurred in patients with advanced disease: MOF (n=7), VOD (n=2), infectious problems associated to GvHD grades II – IV (n=4), and pulmonary embolism (n=l). TREO as part of a myeloablative regimen seems to be effective and safe even in pts not eligible for conventional myeloablative therapy.

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