Years Of Stem Cell Transplantation Research Articles

Thiotepa-Busulfan-Fludarabine in Comparison to Busulfan-Cyclophosphamide As Myeloablative Conditioning Regimen Pre Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Background. Busulfan plus Cyclophosphamide (BuCy) is the traditional myeloablative conditioning (MAC) regimen pre allogeneic stem cell transplantation (SCT) for acute myelogenous leukemia (AML). The Thiotepa, Busulfan, Fludarabine (TBF) protocol was initially developed for cord blood SCT and subsequently employed in haploidentical SCT; however, there is limited data assessing the TBF regimen in SCT from sibling (MSD) and unrelated donor (URD) for AML and no comparison between the two preparative protocols has been performed.Patients and methods. We analyzed transplantation outcomes of 2523 adult patients (pts) with AML in remission (CR1, CR2+) aged 18-50 years that underwent a first SCT from MSD or URD between 2007 and 2015 and reported to the ALWP of the EBMT. One hundred and three patients received TBF and 2370 pts received BuCy. Pts who received oral busulfan, manipulated grafts, or transplant from <=8/10 HLA-matched donor were excluded. All pts received MAC regimen (defined by Busulfan dose>=9.6 mg/kg). As compared to BuCy, the TBF group included significantly older pts, who were transplanted more recently, had longer interval from diagnosis to transplant, and were more likely to have received BM as stem cell source and URD as donor type. In order to minimize the bias due to differences in pts characteristics, a 1:3 pair-matched analysis was performed. One hundred and forty-six pts receiving TBF were compared with 438 pts receiving BuCy; matching factors included age, year of SCT, disease status at SCT, interval from diagnosis to SCT, donor type, CMV serostatus of both the donor and patient, stem cell source, GVHD prophylaxis and use of anti-thymocyte globulin.Results. With a median follow-up of 22 months, incidence of grade II-IV and III-IV aGVHD after TBF vs BuCy was 29% vs 23% (p=0.23) and 15% vs 8% (p=0.04), respectively. The 5-year cumulative incidence of cGVHD and severe cGVHD was 36% vs 43% (p=0.66) and 16% vs 22% (p=0.72) for TBF vs BuCy, respectively. The 1-year and 5-year non-relapse mortality (NRM) rates were 10% and 22% for TBF vs 9% and 13% for BuCy, respectively (p=0.36). The 1-year and 5-year relapse incidence (RI) rates were 17% and 25% for TBF vs 21% and 37% for BuCy, respectively (p=0.32). No significant difference was observed in leukemia-free survival (LFS), being the 1-year and 5-year LFS rates 73% and 53% for TBF vs 70% and 50% for BuCy, respectively (p=0.56). Overall survival (OS) was also similar, being 80% and 54% for TBF vs 79% and 59% for BuCy, respectively (p=0.88). The composite endpoint graft-vs-host disease-free, relapse-free survival (GRFS) at 5 years was 48% for TBF and 40% for BuCy (p=0.48). Notably, when the analysis was restricted to pts in CR1, a significant difference in RI rate was observed (1-year and 5-year RI: 10% and 18% for TBF vs 20% and 38% for BuCy, respectively, p=0.003) leading to a trend for better LFS for TBF as compared to BuCy (1-year and 5-year LFS: 78% and 57% for TBF vs 72% and 50% for BuCy, respectively, p=0.07), with no difference in OS. When examining separately pts receiving SCT from MSD or URD, no significant difference was observed between TBF and BuCy regimens in terms of transplant outcome. In multivariate analysis, TBF was associated with lower RI compared to BuCy (HR 0.6, p=0.02), while no difference was observed in terms of NRM, LFS, OS and GRFS (HR 0.8, p=0.12 for GRFS). TBF was also associated with lower incidence of cGVHD (HR 0.7, p=0.04) and a trend for lower incidence of severe cGVHD (HR 0.6, p=0.1); on the contrary we observed a trend for higher incidence of grade III-IV aGVHD following TBF as compared to BuCy (HR 1.79, p=0.06).Conclusions. These results suggest that TBF is a valid myeloablative conditioning pre MSD or URD SCT for AML pts < 50 years of age and in remission, with similar transplantation outcome as compared to the traditional BuCy preparative regimen. These data may serve as the scientific background for a well designed randomized two arm study comparing TBF to BuCy as MAC pre SCT in AML pts below the age of 50 years in CR. [Display omitted] DisclosuresSavani:Jazz Pharmaceuticals: Speakers Bureau.

Long-Term Follow-up of the Randomized Controlled Study in Patients with Newly Diagnosed Severe Aplastic Anemia Treated with ATG, Cyclosporine, with or without G-CSF: On Behalf of the SAA Working Party of the EBMT

Long-Term Follow-up of the Randomized Controlled Study in Patients with Newly Diagnosed Severe Aplastic Anemia Treated with ATG, Cyclosporine, with or without G-CSF: On Behalf of the SAA Working Party of the EBMT

Stem Cell Transplantation for Pediatric Patients with Non-Anaplastic Peripheral T-Cell Lymphoma on Behalf of the EBMT-Pediatric Diseases Working Party

Peripheral T-cell lymphomas (PTCL) other than anaplastic large cell lymphoma are rare in children, and data about outcome and treatment results especially regarding the role of stem cell transplantation (SCT) are scarce. Here we present the results of a retrospective study of SCT for pediatric patients with PTCL within the European Group of Bone marrow transplantation (EBMT). Out of 125 patients aged <18 years with PTCL diagnosed between 1995 and 2015 who were registered to the EBMT database, reports about the primary therapy and data about the course of SCT were sufficient for analysis in 55 patients. 37 (69%) had PTCL not otherwise specified (NOS), 7 (13%) hepato-splenic T-cell lymphoma, 4 (7%) angioimmunoblastic T-cell lymphoma, 3 (6%) NK/T-cell lymphoma, 2 (4%) subcutaneous panniculitis-like T-cell lymphoma, and 1 systemic EBV-lymphoproliferative syndrome. Median age at PTCL-diagnosis was 13.0 years (range: 0.7-17.6), and was 13.9 years (range: 2.5-17.9) at SCT, respectively. 35 (65%) of the patients were male. 43 (81%) of the patients had received T-NHL/ lymphoblastic lymphoma-type therapy; radiotherapy (RT) was given to 7 patients (16%) prior to SCT. 45 (83%) patients underwent allogeneic SCT (16 from related and 29 from unrelated donor), and 9 (17%) patients received autologous SCT (ASCT). Myeloablative conditioning (MAC) was used in 44 (88%) patients, 6 (12%) patients received reduced-intensity conditioning (RIC). Total body irradiation (TBI) was part of the conditioning regimen in 26 patients (48%).After SCT the 5-year overall survival (OS) and lymphoma-free survival (LFS) probability was 57% (95% CI 44.5-72.5) and 56% (95% CI 43.4-71.2), respectively. Relapse incidence was 25% (95% CI 14.1-37.9), whereas the non-relapse mortality (NRM) rate was 18% (95% CI 9.4-29.7).Patients with younger age (0-9 years, vs. 10-18 years) at diagnosis of PTCL had a tendency for better outcome (OS 80% vs. 50%, respectively p=0.069), whereas age at SCT and gender had no influence on outcome (p=0.2 and p=0.6, respectively). Year of SCT (1995-2007 vs. 2008-2015) was of no significance for the outcome (p=0.31).A tendency for better outcome (OS/LFS) was observed in patients who received RT in the pre-transplant treatment, and for patients who achieved first/second complete remission (CR1/CR2) before SCT, as compared to those with later/ without CR prior to SCT (OS 72% vs 46%, p=0.1). Patients receiving MAC conditioning had a better OS compared to patients receiving RIC (66% vs. 33%, p=0.07). LFS was inferior after ASCT compared to allogeneic SCT, resulting in non-significant difference in OS .Acute Graft-versus host disease (aGvHD) grade III/IV was seen in 6 (14.6%) patients. 6 patients suffered from chronic GvHD, 2 of them from the extensive form.In conclusion, SCT for pediatric patients with PTCL in CR1/CR2 is a valid option of treatment. MAC may currently be chosen for conditioning in order to possibly prevent relapses. DisclosuresBader:Neovii: Research Funding; Cellgene: Consultancy; Riemser: Research Funding; Novartis: Consultancy, Speakers Bureau; Medac: Patents & Royalties, Research Funding.

Tandem high-dose chemotherapy and autologous hematopoietic stem cell transplantation (SCT) compared to single SCT for relapsed/refractory germ cell tumors (GCT).

572 Background: Single-center observational studies have established the use of single or tandem SCT to salvage relapsed GCT but randomized trials are lacking. We analyzed outcomes and prognostic factors in 2,395 male SCT recipients for relapsed GCT between 1990 and 2015. Methods: Recipients of single or tandem SCT reported to the Center for International Blood and Marrow Transplant Research were identified. Outcomes were compared by SCT year: 1990-94 (N = 288), 1995-99 (N = 351), 2000-04 (N = 376), 2005-09 (N = 509) and 2010-15 (N = 871). A recent subset (n = 267, 2000-2015) with detailed disease- and transplant-related data was further analyzed with a multivariate (MVA) Cox proportional hazards model. Results: Median age at SCT was 31 (11-76) years and 49% received SCT within 12 months of diagnosis consistent with early relapse/primary refractory GCT. 26% had primary extragonadal GCT; 1,167 (49%) had intent to tandem transplant (TT). The median follow up was 51 (3-313) months. Day 100 non-relapse mortality was statistically similar at 8% in 1990-94 (vs. 4% in 2010-15) but 3-year progression-free survival (PFS) improved from 24 (18-31)% in 1990-94 to 47 (43-50)% in 2010-15 (p &lt; 0.0001) and 3-year survival (OS) from 35 (29-40)% to 54 (50-57)% in 2010-15 (p &lt; 0.0001). Compared with single SCT, TT recipients were younger 31 (16-62) vs 34 (13-76), with lower Hematopoietic Cell Transplantation-Comorbidity Index, more likely to undergo SCT after 1 line of chemotherapy (28% vs 9%), and within 1 year of diagnosis (51% vs 38%). TT was preferred over single SCT over time (48% of SCT were TT in 2000-04 vs. 81% in 2010-15). In MVA, non-seminoma histology, residual tumor at SCT, receipt of &gt; 1 line of pre-SCT chemotherapy and single SCT (vs. TT), were associated with worse PFS and OS. Year of SCT was not significant when adjusted for these covariates. Conclusions: In this large longitudinal cohort, improvements in PFS and OS were observed in recent years. SCT earlier in disease course and tandem SCT were associated with superior outcomes. These data involving a large cohort reported from 225 centers confirm specialized centers’ date in a real-world setting.

Efficacy of immune suppression tapering in treating relapse after reduced intensity allogeneic stem cell transplantation.

For patients who relapse after allogeneic hematopoietic stem cell transplantation while still on immune suppression, there is anecdotal evidence that tapering the immune suppression may result in graft-versus-tumor activity. We reviewed the medical records of all patients with documented histological or radiographic disease recurrence within 1 year of stem cell transplantation while on immune suppression at our institution. The median time to relapse was 110 days (range, 18-311) after transplant. Among 123 patients with relapse treated with immune suppression tapering without chemotherapy, radiation, or donor lymphocyte infusion, 34 responded (33/101 reduced intensity conditioning transplant and 1/22 myeloablative conditioning transplant, 32.7% and 4.5% respectively; P=0.007). The median time to response after initiation of immune suppression tapering was 82 days (range, 16-189). Thirty-three patients (97.1%) had development or progression of acute or chronic graft-versus-host disease as a consequence of immune suppression tapering, at a median time of 39 days (range, 16-98). Six patients subsequently relapsed late after initial response to immune suppression tapering at a median time of 2 years (range, 0.9-3.8). The median overall survival from immune suppression tapering for responders was 5.1 years (range, 1.9-not estimable). When clinically feasible, immune suppression tapering alone in patients who relapse early after reduced intensity conditioning allogeneic stem cell transplantation can produce durable remissions, but is almost always associated with graft-versus-host disease.

Survival Outcome and Long-Term Follow-up of Autologous and Allogeneic Stem Cell Transplantation (SCT) in Acute Myeloid Leukemia (AML): A 30 Years Single-Center Experience

Background:Post-remission treatment for AML is very aggressive and many times a SCT is needed. Comparisons between Allo-SCT and Auto-SCT ve always shown more Transplant Related Mortality (TRM) but less Cumulative Incidence of Relapse (CIR) in the first group. Our study describes, not only the long-term survival outcomes, but also the quality of life in long survivors.Methods:Retrospective study of 274 patients diagnosed with non-promyelocytic AML who underwent SCT between 1982 and 2011 in our center. Characteristics in the 162 Allo-SCT and the 112 Auto-SCT groups of patients were respectively: median age of 38 and 45 years old, secondary AML in 20% and 10%, refractory to Induction AML in 16% and 3%, pre-SCT status different from Complete Remission (CR) in 13% and 3% and year of SCT before 2005 in 53% and 86%. No significant differences between both groups were found in other risk factors as hyperleucocytosis at diagnosis or adverse cytogenetics.Results:With a median follow-up of 55 months [2-316], Overall Survival (OS) until 1997 in Allo-SCT and Auto-SCT were respectively, 40% and 61% at 1 year and 28% and 45% at 5 years (figure 1), but from 1997, 66% and 70% at 1 year and 47% and 48% at 5 years (figure 2). Disease Free Survival (DFS) until 1997 in Allo-SCT and Auto-SCT were respectively, 50% and 65% at 1 year and 38% and 46% at 5 years, but from 1997, 67% and 63% at 1 year and 52% and 47% at 5 years. In the last 15 years, no differences were found between both groups in OS nor DFS. CIR in Allo-SCT and Auto-SCT were respectively, 18% and 32% at 1 year and 24% and 50% at 5 years, without dependence on year of SCT. No relapse was observed later in any group. TRM until 1997 in Allo-SCT and Auto-SCT were respectively, 30% and 7% at 1 year and 35% and 9% at 5 years, but from 1997, 16% and 2% at 1 year and 25% and 4% at 5 years. Multivariable analysis showed that the only risk factor with a negative impact on OS was not having achieved CR at the time of SCT. Other variables as older age, hyperleucocytosis at diagnosis, adverse cytogenetics, secondary AML or sooner year of SCT lost their univariable analysis significance.Allo-SCT: From the 162 patients, 72(44%) are alive by this moment, 43(60%) with ECOG 0, 21(29%) with ECOG 1 and the other 8(11%) with ECOG 2, basically because of graft versus host disease (GVHD in 39 patients, 21 steroid-dependent and 3 refractory to any treatment). All of them have been in CR during the last 2 years of follow-up. In contrast, 90(56%) patients have died: 52(58%) because of SCT complications (20 infections, 16 GVHD, 8 toxicity and 8 mixed causes), 33(37%) because of disease and 5(5%) because of other causes. With a median follow-up of 43 months [2-316], there have been 4 secondary neoplasm, all of them solid ones, which appeared with a median of 242 months [179-311] from SCT. None of them had previously received radiotherapy.Auto-SCT: From the 112 patients, 43(38%) are alive by this moment, 32(74%) with ECOG 0 and the other 11(26%) with ECOG 1. All of them have been in CR during the last 2 years of follow-up. In contrast, 69(62%) patients have died: 45(65%) because of disease, 14(20%) because of SCT complications and 10(15%) because of other causes. With a median follow-up of 93 months [5-230], there have been 6 secondary neoplasm, 5 of them hematologic ones, which appeared with a median of 90 months [76-115] from SCT. None of them had received radiotherapy, but previously treated hematopoietic stem cells. Only one is alive at the time of last follow-up.Conclusions:In one hand, despite the high incidence of relapse in Auto-SCT in any period, OS is lower in Allo-SCT during the first years [1982-1996], although it has a tendency towards OS in Auto-SCT from 1997 because of the decrease in TRM, which is more significative in Allo-SCT. In the other hand, DFS is slightly higher in Allo-SCT during the last years [1997-2011], although the quality of life in long survivors is worse, basically because of GVHD.In summary, we have not really found differences between Allo-SCT and Auto-SCT in terms of OS and DFS in our series, so both procedures are efficient to treat AML (near 50% of the patients in both groups are alive at 5 years from SCT in recent years). The decrease in TRM until 4% at 5 years in Auto-SCT makes it a good choice, particularly for older patients without risk factors. However, the development of secondary hematologic neoplasms is a relevant fact, with an incidence of 11% and a high late mortality. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Does the Addition of Involved Field Radiotherapy to High-Dose Chemotherapy and Stem Cell Transplantation Improve Outcomes for Patients With Relapsed/Refractory Hodgkin Lymphoma?

To evaluate the value of adding involved field radiotherapy (IFRT) to patients with relapsed/refractory Hodgkin lymphoma (HL) undergoing high-dose chemotherapy (HDCT) and stem cell transplantation (SCT). Ninety-two patients with relapsed/refractory HL undergoing HDCT and SCT from 1995 to 2008 were analyzed in a case-control design. Forty-six HL patients treated with IFRT within 2 months of SCT were matched to 46 HL patients who did not receive IFRT based on age, stage at relapse, timing of relapse, histology, and year of SCT. All were evaluated for response, survival, and toxicity with a median followup of 63.5 months. There was a trend for better disease control in patients receiving IFRT. Specifically, 10/46 IFRT patients (22%) relapsed/progressed after SCT compared with 17/46 control patients (37%). Of the failures after IFRT, 70% were inside the radiation field, all in sites of bulky disease. In patients with nonbulky disease, IFRT also resulted in significantly improved outcomes (failure rate 6% vs. 33%, respectively). When stratified by disease bulk, the use of IFRT was found to significantly improve DFS (p=0.032), but did not affect OS. In addition, IFRT and nonbulky disease were found to be positive prognostic indicators for DFS with hazard ratios of 0.357 (p=0.032) and 0.383 (p=0.034), respectively. Grade IV/V toxicities were significantly higher in the IFRT vs. non-IFRT group (28% vs. 2%; p<0.001), observed only in patients receiving a busulfan-based conditioning regimen. Patients with refractory or relapsed HL undergoing HDCT and SCT have a high risk of relapse in sites of prior disease involvement, especially in sites of bulky disease. The use of IFRT is associated with a lower risk of disease progression in these sites; however bulky disease sites are still difficult to control. Toxicity risk is significant, particularly when busulfan-based conditioning is combined with IFRT, and alternative chemotherapy conditioning regimens should be considered.

Donor Lymphocyte Infusions (DLI) After Peripheral Blood Stem Cell Transplantation. A Retrospective Analysis of 357 Patients by the Chronic Leukemias Working Party EBMT.

Abstract 3309Poster Board III-197Donor Lymphocyte Infusions (DLI) constitute a potent therapeutic option for treating relapse of chronic myelogenous leukemia (CML) after hematopoietic stem cell transplantation (SCT) inducing durable remissions in the majority of patients. A number of factors is known to influence the efficiency of DLI. A preliminary analysis of EBMT data had suggested that DLI efficiency might be inferior after peripheral blood stem cell transplantation (PBSCT) as compared to DLI following bone marrow transplantation (BMT) (Schmid et al. ASH, 2005). To control for a number of other factors that were not known at the time of the previous analysis, we repeated this analysis based on the results of 357 patients treated with DLI following PBSCT (N=108) and BMT (N=249). We limited the analysis to patients who relapsed after standard intensity conditioning SCT from HLA-identical family donors in first chronic phase of disease. The median age of patients was 39 years (range 18-60) with predominance of males (59%). 53% of patients with known data were CMV positive and in 44% of the patients there was a sex-mismatch with the stem cell donor. SCTs have been performed between 1994 and 2007 (median year: 1998) and the conditioning treatment included total body irradiation (TBI) in 68% and T cell depletion in 44% of patients. 92% of patients with known data achieved complete remission after SCT while grade II-IV acute GvHD occurred in 18% of patients and extensive chronic GvHD in 17% of patients. Median time to relapse was 17 months (range 0.6-129) and median time from SCT to first DLI infusion was 23 months (range 0.6-142). Looking at the patients with known data at the time of first DLI infusion, the relapse could be classified as molecular/cytogenetic in 63%, hematologic in 27% and transformed in 10% of patients. The median year of first DLI was 2000 ranging from 1995 to 2007. As the initial DLI infusion, 9% of patients received <1×10e6, 62% 1.1-10×10e6 and 29% received >10×10e6 CD3+ cells/kg. However, the comparative analysis of groups based on the stem cell source revealed that the group of patients transplanted with PBSCs included significantly more males (68 vs. 56%), were older (median age 42 vs. 39) and underwent more frequently T cell depletion at SCT (72 vs. 34%,). PBSCTs have been performed more recently (median year 1999 vs. 1997) and both duration of remission and time from SCT to first DLI were shorter after PBSCT (median duration: 12 vs. 21 months and 14 vs. 26 months respectively). The initial cell dose in patients from PBSCT arm was significantly lower than in BMT group (≤10×10e6 CD3+/kg in 89% vs. 65% of patients). Similarly to the previous study, we also observed a trend towards superior overall survival after DLI in BMT group compared to PBSCT group, especially in the early post-transplant period. The actuarial probability of survival at five years from DLI was 77% in PBSCT group and 79% in BMT group. However the differences were not statistically significant (p=0.77). The source of stem cells did not influence the occurrence of molecular/cytogenetic remissions after DLI (80% vs. 77%) grade II-IV acute GVHD (16% vs. 16%), chronic GVHD (23% vs. 30%) and myelosuppression (10% vs. 16%). In order to search for factors having impact on survival of analyzed patients, we performed both univariate and multivariate survival analyses. The univariate analysis revealed that interval from SCT to DLI longer than 2 years (p=0.001), date of DLI after 2000 (p=0.026) and molecular/cytogenetic stage of relapse at DLI (p<0.001) were associated with favorable survival. Similarly, the multivariate Cox analysis identified interval between SCT and DLI (HR= 0.50, CI: 0.3-0.8; p=0.01 for after 2 years), date of DLI (HR=0.63, CI:0.4-1.0; p=0.07 for after 1999), and stage of relapse (HR=2.8, CI:1.2-6.5; p=0.02 for HemCR and HR=3.6, CI:1.8-7.0; p<0.001 for missing data group), but not for stem cell source (HR=0.95, CI 0.56-1.6 ;p=0.86) as independent factors affecting survival. Based on our retrospective data from EBMT registry covering a period of 14 years of SCT and DLI, it seems that the PBSCT does not affect the efficiency of DLI compared to BMT. Therefore, keeping all limitations of a retrospective analysis in mind, it seems that differences in efficacy of DLI do not influence the decision whether PBSC or BM should be used as stem cell source for allogeneic SCT in CML in first chronic phase. DisclosuresNo relevant conflicts of interest to declare.

India’s stem cell research and development perspectives

We find the review article by Au et al. [1] remarkable andtimely. It portrays India’s recent scenario of stem cellresearch and development. We would like to state furtherthat scientists and medical doctors in India also contribute alot for the technical developments in stem cell researchwith a great potential to tackle India’s future health prob-lems. Perhaps, it is time to remember that India, in 2008has completed 25 years of stem cell transplantation (SCT).India’s first allogeneic bone marrow transplantation (BMT)(one type of SCT) was performed on 20 March 1983 atTata Memorial Hospital VK (File No AP 14703). A 9-year-old girl patient was then suffering from the disease of acutemyeloid leukemia (AML). After BMT, she fully recoveredand currently enjoying a married and employed life, whichis an excellent example of cancer cure through SCT inIndia. For several life-threatening diseases, the SCT prac-tice appears to be a life saving procedure. In India, over20 million carriers and 10,000 children are born each yearwith thalassemia major. Allogeneic SCT is the only curefor thalassemia major, and is cost-effective compared toconventional blood transfusions and iron chelation therapy.The major portion of BMT for thalassemia has been per-formed by the Christian Medical College (CMC) inVellore, south India [2]. In this hospital, 626 transplantshave been performed in 595 patients between October 1986and December 2006. More than one transplant had beenperformed in case of 28 patients [3] (Fig. 1). BMT ofthalassemia accounts for a third of these total transplantsduring this period. Chronic myeloid leukemia (CML) canbe treated with drugs like interferon. This disease can alsobe potentially curable with allogeneic SCT. The cost perallogeneic SCT is much less than the cost of interferontherapy added that period of life. The major portion of SCTin CML has carried by Tata Memorial Hospital, Mumbaiand the SCT can treat other diseases like aplastic anemia,Fanconis anemia, most acute leukemias, myelodysplasiaand certain lymphomas (Fig. 1). For these diseases, a totalof 1540 transplants have been performed during September2005 in six different transplantation centers in India [3].The cost of BMT is about USD 20,000 in India’s besthospitals while in developed countries such as the UK andUSA, it would exceed 4–5 times. Similarly, in other Asiancountries, the cost is higher and in Thailand for example,the cost for BMT is USD 62,500. The lower health carecost is currently boosting medical tourism in India whenIndia’s domestic population has crossed 1.15 billion in2008. As a result, the burden of patients in the existing fewtransplantation centers is increasing; therefore, moretransplant centers are urgently needed in major cities acrossIndia.In the UK, the World’s first stem cell bank was estab-lished in 2003 at Hertfordshire, which is being managed bythe National Institute of Biological Standards (NIBSC) andfunded by the Medical Research Council (MRC) and theBiotechnology and Biological Sciences Research Council(BBSRC). Subsequently, stem cell banks were establishedin all continents except Africa, which is yet to open a cordblood bank (Fig. 2). At present, over 100 cord blood bankshave been established globally. Accordingly in India, theReliance life Sciences (RLS), a Reliance group of

Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Allogeneic stem cell transplantation is a potentially curative treatment for myelofibrosis, although its use is limited by a high rate of transplant-related mortality. In this study, we evaluated the outcome of patients with myelofibrosis who underwent allogeneic stem cell transplantation, and the impact of prognostic factors. One hundred patients were transplanted in 26 Italian centers between 1986 and 2006. We analyzed the influence of the patients' characteristics and the clinical features of their disease before stem cell transplantation and of transplant procedures on transplant-related mortality, overall survival, and relapse-free survival by means of univariate and multivariate analyses. The median age of the patients at the time of stem cell transplantation was 49 years (range, 21-68) and 90% of them had an intermediate or high Dupriez score. Forty-eight percent received a myeloablative conditioning regimen and 78% received stem cells from matched sibling donors. The cumulative incidence of engraftment at day 90 after transplant was 87% (95% CI, 0.87-0.97). The cumulative 1-year and 3-year incidences of transplant-related mortality were 35% and 43%, respectively. The estimated 3-year overall and relapse-free survival rates after stem cell transplantation were 42% and 35%, respectively. In multivariate analysis, negative predictors of transplant-related mortality were year of stem cell transplantation before 1995, unrelated donor, and a long interval between diagnosis and transplantation. There was a trend towards longer overall and relapse-free survival in patients receiving peripheral blood stem cells rather than bone marrow as the source of their graft (p=0.070 and p=0.077, respectively). The intensity of the conditioning regimen (myeloablative versus reduced intensity regimens) did not significantly influence the outcome. We conclude that the outcome of myelofibrosis patients who underwent allogeneic stem cell transplantation significantly improved after 1996 due to the reduction in transplant-related mortality. We observed that a reduction in transplant-related mortality was associated with the choice of a matched sibling donor, whereas longer overall survival was associated with the use of peripheral blood as the source of stem cells.

Fatal Infectious Complications Developing Late after Allogeneic Stem Cell Transplantation.

Background and aim: The procedure of allogeneic stem cell transplantation (SCT) has evolved during the past decades. Infectious complications are still a major problem contributing to the transplantation related mortality (TRM). The epidemiology and outcome of early infections after SCT are well described. However, less is known has about late infections after SCT. Thus, the aim of this study was to determine risk factors for fatal infections occurring later than 6 months after allogeneic SCT.Material and methods: Our study is based on 938 consecutive SCT patients transplanted 1976–2003 of whom 688 (73%) had survived for at least 6 months after SCT. A retrospective chart review was performed identifying 44 (6.4%) patients surviving for at least 6 months, having died from infection. Patients who had relapsed in their malignant disease were excluded. A control group of 176 patients (4 per case) was identified using relapse-free survival for at least 6 months and year of SCT as the matching criteria. Five controls were excluded leaving 171 patients in the control population. Risk factors for death from late infections were identified by logistic regression.Results: 29 patients (66%) developed their fatal infection within 18 months and 37 (84%) within 5 years after SCT. 37 patients (84%) had ongoing chronic graft versus host disease (GVHD) and 36/44 (82%) had ongoing immunosupression at the time of death. 57 controls had died after 6 months from SCT; 32 of 57 from relapse. Comparing patients and controls in univariate analyses, the mean age was 30.6 years in the cases and 26.5 years in the controls (p=.13). 22/44 (50%) cases had been transplanted from an unrelated or mismatched donor, compared to 57/171 (33%) controls, p=.053; and 35/44 (80%) cases had received a conditioning regimen including myeloablative dose of TBI compared to 113/171 (66%) in the control group, p<.05). Regarding post-transplant complications 40/44 (91%) cases had experienced cGVHD compared with 101/171 (59%) controls, p<.001. 21/44 (48%) cases had developed obstructive respiratory dysfunction compared with 46/171 (27%) controls, p=.01; and more cases (33/44; 75%) than controls (85/171; 50%;) had experienced CMV infection. In multivariate analysis chronic GVHD (OR 9.2; p<.001), use of a mismatched or unrelated donor (OR 4.8; p<.001), and having had a CMV reactivation (OR 8.3; p=.004) increased the risk. Age, acute GVHD, TBI or obstructive respiratory dysfunction had no significant impact on the risk for late fatal infection.Conclusion: Infections later than 6 months after SCT are important contributors to late TRM. Risk factors for late fatal infections include chronic GVHD, use of alternative donors and CMV infection.

Circulating dendritic cell subset levels after allogeneic stem cell transplantation in children correlate with time post transplant and severity of acute graft-versus-host disease

We examined the recovery of circulating monocytoid (Lin- CD11+ HLA-DR+) and plasmacytoid (Lin- CD123+ HLA-DR+) precursor (pre) dendritic cell (DC) subsets after allogeneic stem cell transplantation (SCT) in 39 children, using age-matched healthy children as controls. The frequencies of DCs in peripheral blood samples were determined by flow cytometry. The initial recovery of DC occurred simultaneously with myeloid engraftment. However, with time, DC subset values declined, being very low 40-50 days after SCT. Low monocytoid and plasmacytoid DC values were associated significantly with the development of severe acute graft-versus-host disease (aGVHD) (P=0.042 and 0.017, respectively). Plasmacytoid DC values were lower than in the age-matched controls for the entire follow-up period (range 102-2569 days), although, with time, values approached normal levels. Normal monocytoid DC numbers were observed within 300-400 days post SCT. The severity of chronic GVHD did not correlate with quantitative recovery of DC. We conclude that in pediatric SCT, initial recovery of DC production is concurrent with that of myelopoiesis, yet with time, DC subset values decline and low counts are associated with severe aGVHD. Monocytoid DC numbers approach normal levels within a year of SCT, but plasmacytoid DC counts recover very slowly.