Allogeneic HSCT for Patients Aged More Than 55 Years with Myeloid Malignancies: Results of 171 Patients

Abstract Background: Incidence of most myeloid malignancies increases with age. Although allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative option for most of myeloid diseases, conventional myeloablative regimens are associated with considerable toxicity in older patients and high rate of non-relapse mortality (NRM). Thus, such standard approach is very rarely performed in the setting of older patients. Recent developments and introduction of reduced intensity\toxicity (RIC/RTC) and non-myeloablative (NMAC) regimens have allowed the extension of Allo-HSCT to these older patients. This study aims to report our experience of Allo-HSCT in patients > 55 years of age. Patients and Methods: From 2005 to 2014, 171 patients > 55 years of age with myeloid malignancies underwent first allogeneic HSCT at our center, with a median age of 63 years (56-72 years). Sixty-five patients (38%) had 65 years or more. Data had been double-checked using individual institutional files along with HSCT database of the IPC. Of all patients 117 had AML, 49 had MDS and 5 had MPN. They were conditioned by RIC (120 patients, 70%), RTC (16 patients, 9%) or NMAC (35 patients, 21%) regimens. One hundred and nineteen patients (70%) were transplanted with HLA-identical donor (sibling donor, n=66; unrelated donor; n=53), while 52 patients (30%) received transplantation from alternative donor (mismatched unrelated donor, n=18; cord blood, n=14; haploidentical donor, n=20). We found that 91 patients (53%) have a hematopoietic cell transplantation comorbidity index (HCT-CI) between 0 and 2, while 80 patients (47%) had a HCT-CI ≥ 3. Disease risk index (DRI) was low, intermediate, high and very high in 4 (2%), 108 (63%), 55 (33%) and 4 (2%) patients, respectively. Results: NRM at day+100 and 3 years were 7% and 23%, respectively. Cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 20% and 28%, respectively. With a median follow-up of 32 months (3.3-99.5), 3-years cumulative incidence of relapse (CIR), overall survival (OS) and progression free-survival (PFS) were 32%, 52% and 45%, respectively. Although we found a trend for higher NRM in patients aged above 65 years (< 65 vs. >= 65 years: 20% vs. 28%, p=0.056), no impact of age was found on PFS (< 65 vs. >= 65 years: 44% vs. 46%, p=0.662) and OS (< 65 vs. >= 65 years: 50% vs. 54%, p=0.750). DRI significantly influenced outcome (low + intermediate vs. high + very high: PFS: 53% vs. 28%, p=0.011; OS: 60% vs. 34%, p=0.020) while patients who received NMAC regimens had significantly lower PFS (NMAC vs. RIC vs. RTC: PFS: 26% vs. 50% vs. 50%, p=0.028) and OS (NMAC vs. RIC vs. RTC: PFS: 30% vs. 57% vs. 63%, p=0.031).There were no significant differences of OS or PFS among patients groups classified according to type of donor, sex mismatch, donors' age, donors' sex, donors' CMV antibodies positivity, patients' sex, HCT-CI, disease classification, graft's source or whether they were transplanted before or after 2010. In multivariate analysis model including conditioning type (NMAC vs. RIC vs. RTC), DRI (low + intermediate vs. high + very high), HCT-CI (0-2 vs. >=3), patients' age (continuous) and donors' type (HLA-identical vs. alternative donor), high/very high DRI as well as the use of NMAC regimens were independent poor predictive factor associated with higher CIR and shorter PFS (HR, 95%CI=1.77, 1.16-2.72; p=0.009 for DRI; HR, 95% CI=1.87, 1.11-3.13; p=0.018 for NMAC) and OS (HR, 95% CI=1.75, 1.11-2.75; p=0.016 for DRI; HR, 95% CI=1.98, 1.14-3.45; p=0.016 for NMAC). Patient's age was associated with higher NRM (HR, 95% CI=1.10, 1.01-1.19; p=0.027). Conclusion: Our data shows that though aged patients still generally at a higher risk of NRM, Allo-HSCT using adapted conditioning regimen can provide low NRM and prolonged survival. Beyond the feasibility, disease relapse appears as the major issue after Allo-HSCT. To optimize conditioning regimen for older patients may be a viable option to enhance disease control without raising toxicity. Indeed, the development of RIC/RTC regimens may improve overall outcome of older patients suffering from myeloid diseases. In contrast, truly NMAC regimens may provide insufficient disease control. The optimal conditioning intensity in the setting of older patients with myeloid malignancies remains undefined and should be evaluated in further prospective trials. Disclosures No relevant conflicts of interest to declare.

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Allogeneic Stem-Cell Transplantation From Related and Unrelated Donors in Older Patients With Myeloid Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2003.09.110 ◽

2003 ◽

Vol 21 (8) ◽

pp. 1480-1484 ◽

Cited By ~ 128

Author(s):

Hartmut Bertz ◽

Karin Potthoff ◽

Jürgen Finke

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Older Patients ◽

Poor Prognosis ◽

Fungal Infections ◽

Complete Response ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Myeloid Malignancies

Purpose: To improve outcome for older patients with poor-prognosis myeloid malignancies by using allogeneic hematopoietic stem-cell transplantation (alloHSCT) from unrelated and sibling donors after reduced-intensity conditioning (RIC). Patients and Methods: Nineteen older patients (median age, 64 years; range, 60 to 70 years) with active myeloid malignancies were treated with an RIC regimen that was based on fludarabine, melphalan, and carmustine followed by alloHSCT from matched unrelated (n = 12) or sibling donors (n = 7). Before transplantation, patients had a median of 50% bone marrow blasts (range, 0% to 70%). Graft-versus-host-disease (GvHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil or methotrexate. Eleven of 12 patients with an unrelated donor also received anti–T-lymphocyte globulin (ATG). Results: Engraftment was successful for all 19 patients. Seventeen assessable patients achieved complete response (CR). Four patients experienced relapse; three achieved CR again after donor lymphocyte infusion (n = 1) or a second alloHSCT (n = 2). Six patients died as a result of relapse (n = 2), GvHD-associated complications (n = 2), or fungal infections (n = 2), resulting in a 1-year nonrelapse mortality rate of 22%. With a median follow-up of 825 days (range, 595 to 1,028 days), 13 of 19 patients are alive, resulting in a 1-year survival rate of 68% (95% confidence interval, 48% to 89%). Conclusion: In older patients with untreated poor-prognosis leukemia, this RIC regimen combined with alloHSCT sufficiently reduces the leukemic burden, resulting in a high CR rate. When ATG is added, matched unrelated donor transplantation can be performed safely in older patients. For these patients, early transplantation after diagnosis offers a fair chance of cure.

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

Blood ◽

10.1182/blood-2012-04-423822 ◽

2012 ◽

Vol 120 (2) ◽

pp. 473-476 ◽

Cited By ~ 110

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.

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Results of Alternative Donor Search in Adult Patients with Severe Sickle Cell Disease (SCD) Eligible for Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽

10.1182/blood.v110.11.2260.2260 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2260-2260 ◽

Cited By ~ 1

Author(s):

Matthew M. Hsieh ◽

Jennifer Wilder ◽

Courtney Fitzhugh ◽

Beth Link ◽

John F. Tisdale

Keyword(s):

Cord Blood ◽

Great Majority ◽

Hla Typing ◽

Unrelated Donor ◽

Potential Donor ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Sibling Donor ◽

Alternative Donor ◽

Matched Sibling

Abstract Supportive care has improved the outlook for patients with SCD, but life expectancy remains considerably shorter than those without SCD. The major causes of mortality are end-organ failure, stroke, pulmonary disease, and acute vaso-occlusive crises (VOC). Myeloablative allogeneic HSCT in children under age 16 is curative in the majority. However organ damage that meets severity criteria for HSCT may not become evident until adulthood, at which time conventional myeloablative transplant is no longer an option. Additionally, the great majority of SCD patients do not have a 6/6 HLA-matched sibling donor available. Reduced-intensity conditioning may extend this potentially curative treatment to adults with SCD. Since non-myeloablative transplants may result in mixed donor chimerism, major ABO-mismatch may lead to red cell aplasia, and therefore should be avoided. Finally, cell dose is likely an important parameter in non-myeloablative transplant regimens, potentially further limiting donor availability. We initiated an IRB approved non-myeloablative allogeneic HSCT program for adults with severe SCD for whom a matched sibling donor is available. For those without related donors, we devised a search strategy for alternative donors to establish the feasibility of matched unrelated donor (MUD) or umbilical cord blood (UCB) HSCT. HLA typing was performed for potential donors and patients who on initial screen met at least one the following criteria: stroke, pulmonary hypertension, sickle related nephropathy, or frequent VOC/ACS not improved by HU. Typing at the serologic level was performed for HLA-A,-B, and at the allele level for HLA-DR B1. For patients without matched sibling donors, searches in the National Marrow Donor Program for marrow and cord blood donors were initiated. Since 2003, we performed initial screening in >100 patients, typed 58 potential recipients and 85 donors, and identified 13 potential recipients (age ≥ 16 years) with matched sibling donors. Two were excluded because of major ABO incompatibility. Among the remaining 43, 10 patients who met all study criteria on full screening were selected for alternative donor searching. MUD search results identified a median of 2.5 (range 0–18) 6/6 HLA-matched donor available. Five individuals had 0, four had 4–6, and one had >15 potential donors. UCB search revealed no patient had a 6/6 HLA-matched, two had 15–16 5/6 HLA-matched, and five had 11–190 4/6 potential donor UCB units. The median UCB units containing ≥ 2 × 10e7 nucleated cells per kg were 0 for 6/6 HLA-matched (range 0–1), 0 for 5/6 HLA-matched (range 0–19), and 8.5 for 4/6 HLA-matched (range 0–190). When ethnic haplotype and allelic frequency, the available ABO status, the likelihood of requiring two UCB units for each adult recipient were considered, 5 had neither MUD nor UCB units available, 2 only had potential UCB units available, and 3 had both MUD and UCB units available. The majority of adults with severe SCD who are eligible for non-ablative allo-HSCT do not have matched sibling donors. Our search shows that the minority of African-American adults have potential alternative donors, 10% and 50% MUD and UCB, respectively. These numbers will likely be reduced when major ABO mismatches are excluded. Further, unlike pediatric patients, one cord blood unit may not provide sufficient cells to overcome the barrier of graft rejection in most adults. Given these limitations, the feasibility of haplo-identical family donor allo-HSCT should be investigated.

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The Impact of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with Recurring Hodgkin’s Lymphoma: An EBMT Study on 151 Patients.

Blood ◽

10.1182/blood.v110.11.3061.3061 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3061-3061 ◽

Cited By ~ 1

Author(s):

Alexander Claviez ◽

Carmen Canals ◽

Marc Boogaerts ◽

Jerry Stein ◽

Stephen Mackinnon ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Performance Status ◽

Conditioning Regimen ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

The Impact ◽

Time Point

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for patients with recurring Hodgkin’s lymphoma (HL). Standardized inclusion criteria, the optimal time point and the type of conditioning regimen have, however, not been clarified yet. Moreover, high treatment related mortality (TRM) has hampered the widespread use of this procedure. Only few data are available on the impact of allogeneic HSCT in pediatric and adolescent patients. Patients and Methods: We analyzed patients registered in the EBMT Lymphoma Database (age < 21 years at transplantation) who received an allogeneic HSCT for relapsed or refractory HL between 1987 and 2005. Results: A total of 151 patients (56% male) were included. Median age at diagnosis and HSCT was 15 and 18 years, respectively. 57% of patients had received three or more lines of treatment prior to allogeneic HSCT including autologous HSCT in 77 patients with a median interval of 18 months between autologous and allogeneic HSCT. The majority of donors were matched related (63%), followed by matched unrelated (25%) and mismatched donors. A full myeloablative conditioning regimen was given to 40% of patients and 60% received a regimen of reduced intensity. Disease status at HSCT was sensitive (complete or partial remission) in 59% and refractory (no change or progression) in 41%. 23% of the patients developed grade 2–4 acute graft versus host disease (GvHD). Of 35 patients with evaluable chronic GvHD, limited and extensive GvHD were balanced. With a median follow-up of 25 months (maximum 154), 75 patients (50%) are alive and 59 of them disease-free. 56 patients (37%) relapsed after a median time of 5 months (<1 to 36 months) and only 16 were alive at last contact. The probability for progression-free survival (PFS) at 2 and 5 years were 39% and 29% respectively. The cumulative incidences (CI) for relapse at 1, 2 and 5 years were 29%, 37% and 44%, respectively, whereas the CI for TRM at 1, 2 and 5 years were 20%, 24% and 27%, respectively. In multivariate analysis, HLA disparity (p=.002), HSCT before 2001 (p=.01) and female sex (p=.02) were associated with a higher TRM, while poor performance status (p=.005) and refractory disease (p=.04) resulted in an inferior PFS. Reduced treatment intensity had no impact on relapse rate within one year after HSCT but was associated with a higher incidence of relapse (p=.02) beyond 12 months. The PFS and TRM of patients without adverse prognostic factors (HSCT >2001, matched donors and good performance status at HSCT) at 1, 2 and 5 years was 67%, 50% and 43%, and 11%, 17% and 17%, respectively. Conclusion: This study of young patients with HL receiving allogeneic HSCT indicates a comparable outcome to adult patients. Transplantation was beneficial especially for patients with a good performance status, HSCT in recent years and available matched donors. Allogeneic HSCT should be carefully selected at an early time point in children failing standardized primary and salvage treatment.

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Intravenous Busulfan-Based Myeloablative Conditioning Is Comparable to TBI-Based Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Recipients with Acute Myeloid Leukemia: A Nationwide Retrospective Study From the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Blood ◽

10.1182/blood.v120.21.1922.1922 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1922-1922

Author(s):

Takuya Yamashita ◽

Takahiro Fukuda ◽

Shuichi Taniguchi ◽

Kazuteru Ohashi ◽

Saiko Kurosawa ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Myeloid Leukemia ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Conditioning Regimens ◽

Acute Myeloid

Abstract Abstract 1922 In allogeneic hematopoietic stem cell transplantation (HSCT) for recipients with acute myeloid leukemia (AML), cyclophosphamide (Cy) combined with total body irradiation (TBI) (Cy+TBI) is the most common myeloablative conditioning (MAC) regimen, but busulfan (Bu) in combination with Cy (Bu+Cy) has been an alternative to Cy+TBI since early 1980s. But as oral Bu has a problem of interpatient variation in intestinal absorption, intravenous Bu (ivBu) has been developed and substituted for Bu in conditioning regimens for HSCT. For the last decade, fludarabine (Flu)-based regimens with the addition of cytotoxic agents such as Bu or melphalan (L-PAM) have been developed as reduced-intensity conditioning (RIC) regimens. After the introduction of ivBu, Flu+ivBu has become one of the common RIC regimens. In Japan, ivBu was introduced in 2006 and have been widely used as a part of conditioning regimens. In this nationwide retrospective study, we evaluated the clinical outcomes of allogeneic HSCT for AML, especially focusing on ivBu-based conditioning regimens. The study population included HSCT recipients reported to the Japan Society for Hematopoietic Cell Transplantation. From this database, we extracted the data of adult patients with AML who received first allogeneic HSCT between 1975 and 2010. There were 9,396 recipients selected according to this criterion. Then, we excluded 345 (3.7%) cases from the study because of missing key variables. A total of 9,051 recipients were evaluated in this study. Median age at transplant was 43 years (range, 16–82), and 41.8% (n=3,785) were female. Types of transplant included bone marrow transplantation from sibling donor (RBMT) (n=1,978, 21.9%), peripheral blood stem cell transplantation from sibling donor (RPBSCT) (n=1,411, 15.6%), bone marrow transplantation from unrelated donor (UBMT) (n=3,321, 36.7%) and cord blood transplantation from unrelated donor (CBT) (n=1,728, 19.1%). MAC regimens were applied to 80.2% (n=7,259) of recipients and RIC regimens to 19.8% (n=1,792), according to the definitions proposed by the NMDP and the CIBMTR in 2007. These MAC regimens included Bu+Cy-based (12.4% of all MAC regimens), Cy+TBI-based (50.0%) and ivBu+Cy-based (5.6%) regimens. RIC regimens consisted mainly of Flu+Bu-based (27.6% of all RIC regimens), Flu+L-PAM-based (24.1%) and Flu+ivBu-based (19.5%) regimens. Median follow-up of survivors was 1,437 days (range, 26–8,344). In MAC setting, overall survival (OS) of HSCT recipients with ivBu+Cy-based regimens did not show the significant difference between that with Bu+Cy or Cy+TBI-based ones in RBMT (p=0.168), RPBSCT (p=0.236) and UBMT (p=0.604). But in CBT, Cy+TBI was significantly superior to Bu+Cy (p=0.004). Though the cumulative incidences of relapse (RI) were similar among recipients with these three regimens, the cumulative incidence of non-relapse mortality (NRM) with Bu+Cy was significantly higher than with Cy+TBI in CBT (p=0.049). In RIC setting, OS of recipients with Flu+ivBu-based regimens was comparable to that with Flu+Bu or Flu+L-PAM-based ones regardless of the type of transplant. RIs with these three regimens were almost equivalent, but NRM with Flu+ivBu-based was significantly lower than that with Flu+L-PAM-based in UBMT (p=0.023). In the multivariate analysis for OS, ivBu+Cy-based regimens did not have significant impacts regardless of the type of transplant, but Flu+ivBu-based regimen had a significantly favorable impact in RBMT (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.23–0.99). In the multivariate analysis for NRM, Flu+ivBu-based regimen had a significantly reduced risk compared with Flu+L-PAM in RBMT (HR 0.32, 95%CI 0.11–0.95) and UBMT (HR 0.46, 95%CI 0.25–0.83). These data indicates that ivBu+Cy-based and Cy+TBI-based MAC regimens have almost equivalent efficacy profiles for OS, RI and NRM, and Flu+ivBu-based RIC regimens can reduce the risk of NRM compared with Flu+Bu and Flu+L-PAM-based ones in allogeneic HSCT for recipients with AML. Disclosures: No relevant conflicts of interest to declare.

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Clinical Outcomes of Haploidentical Donor Compared with Unrelated and HLA-Matched Related Donor Hematopoietic Stem Cell Transplantation for Hematologic Malignancies

Blood ◽

10.1182/blood.v120.21.4159.4159 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4159-4159

Author(s):

Yi Luo ◽

Yamin Tan ◽

Xiaoyu Lai ◽

Weiyan Zheng ◽

Jimin Shi ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conditioning Regimen ◽

Hematologic Malignancies ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Haploidentical Transplantation ◽

Related Donor ◽

Matched Donor

Abstract Abstract 4159 Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for hematologic malignancies. In clinical trials, a HLA-matched donor can only be found for about 50% to 60% of patients referred for HSCT which greatly limit the application of this important procedure. Haploidentical HSCT would increase the availability of donors for nearly 100% of patients. However, haploidentical HSCT may be associated with high risks of complications, such as graft rejection, severe GVHD and infection etc. Although great progress have been achieved in haploidentical HSCT based on advanced technologies and novel drugs, no study has simultaneously compared the outcomes of haploidentical, unrelated and HLA-matched related donor HSCT. Materials and Methods: In this study, 225 patients with hematologic malignancies received allo-HSCT from diffent donor sources in our center (69 with haploidentical donors, 62 with HLA-matched related donors and 94 with unrelated donors). The clinical outcomes of haploidentical HSCT cohort, unrelated donor HSCT cohort and HLA-matched related donor HSCT cohort were compared. In HLA-matched sibling and unrelated donor transplantation cohorts, patients received a same conditioning regimen consisting of intravenous busulfan 3.2 mg/kg/d on days –7 to –4, intravenous cyclophosphamide 60 mg/kg/d on days –3 to –2, and 250 mg/m2 of Me-CCNU orally on day -1. For haploidentical HSCT, conditioning regimen consisted of Ara-C (4 g/m2/d) on day -10 and -9, Bu (9.6mg/kg) on day -8, -7 and -6, Cy (1.8 g/m2/d) on day -5 and -4, Me-CCNU (250 mg/kg) on day -3, and ATG (2.5 mg/kg/d) on day -5 to -2. GVHD prophylaxis consisted of cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate while ATG (1.5 mg/kg/d) for three or four days, were added in HLA-matched or mismatched unrelated HSCT. Results: The patients receiving haploidentical HSCT experienced grades III-IV aGVHD more frequently than those receiving unrelated donor HSCT and related matched donor HSCT (24.4% vs 12% vs 2.6% respectively, p<0.05). However the incidence of cGVHD was comparable (17.8% in the haploidentical cohort vs 37.3% in the unrelated donor cohort vs 25.6% in the related matched donor cohort, p>0.05). The transplantation-related mortality (TRM) at d100 were 17.4%, 8.5% and 1.6% in the haploidentical, unrelated and related matched transplantation cohorts respectively (p<0.05). The 3-year relapse incidence were 10.1%, 15.9%, 17.7% in the haploidentical, unrelated and relate matched transplantation cohorts respectively (p>0.05). The 3- year overall survival (OS) was comparable in three cohorts (64.2±6.4% in the haploidentical cohort vs 67.5±5.3% in the unrelated donor cohort vs 77.5±5.8% in the related matched cohort, p>0.05). Conclusion: Although a higher incidence of aGVHD and TRM was observed in the haploidentical transplantation cohort, the incidences of cGVHD and relapse were comparable in the haploidentical, unrelated and related matched transplantation cohorts. Ultimately the patients receiving haploidentical transplantation achieved comparable OS with those receiving unrelated donor transplantation. An HLA-matched HSCT is commonly the preferred transplantation and donors from HLA-matched related siblings are usually the first choice. Haploidentical stem cell transplantation is relatively safe and efficient for patients who do not have HLA matched donors. Disclosures: No relevant conflicts of interest to declare.

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Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation

Blood ◽

10.1182/blood-2002-06-1672 ◽

2002 ◽

Vol 100 (13) ◽

pp. 4367-4371 ◽

Cited By ~ 35

Author(s):

Mark J. DiNubile ◽

Thomas P. Stossel ◽

Olof C. Ljunghusen ◽

James L. M. Ferrara ◽

Joseph H. Antin

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conditioning Regimen ◽

Physiological Role ◽

Actin Binding ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Plasma Gelsolin ◽

Novel Strategy

The idiopathic pneumonia syndrome (IPS) represents a common and often fatal complication of hematopoietic stem cell transplantation (HSCT). Gelsolin is a highly conserved actin-binding protein normally present in plasma that may serve a basic physiological role in limiting acute lung injury of diverse etiologies. We hypothesized that depletion of circulating gelsolin following HSCT might play a permissive role in the pathogenesis of IPS. Plasma gelsolin levels were measured by immunoblotting in frozen samples obtained weekly from 24 patients undergoing allogeneic HSCT. Patients with and without IPS were similar with respect to age, diagnosis, histocompatibility differences between donor and recipient, and conditioning regimen. Mean gelsolin levels in the 9 patients with rapidly fatal IPS were significantly lower than those in patients without this complication by week 3 after HSCT (101 ± 61 mg/L versus 221 ± 54 mg/L; P = .0002). Seven (88%) of the 8 patients with gelsolin levels of less than 100 mg/L in the first month after HSCT died from IPS within 3 months; conversely, gelsolin levels fell to less than 100 mg/L in 7 (78%) of the 9 patients who died from IPS within 3 months of HSCT (P = .0007). These findings suggest that gelsolin levels shortly after allogeneic HSCT can predict the later development of fatal IPS. Gelsolin replacement in selected transplant patients may offer a novel strategy to prevent or reverse IPS.

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The Impact of Age in Allogeneic Stem Cell Transplantation with Thiotepa Busulfan and Fludarabine (TBF) for Myelofibrosis : A Retrospective Analysis

Blood ◽

10.1182/blood-2021-145711 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4858-4858

Author(s):

Federica SORA ◽

Patrizia Chiusolo ◽

Sabrina Giammarco ◽

Idanna Innocenti ◽

Francesco Autore ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Total Dose ◽

Cell Transplantation ◽

Older Patients ◽

Research Funding ◽

Acute Gvhd ◽

Conditioning Regimen ◽

Hematopoietic Stem ◽

The Impact

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) currently remains the only curative therapy for intermediate or high risk disease.myelofibrosis (MF). We are reporting 56 patients (pts) who underwent an allogeneic HSCT in our Centre between 2016 and 2020, and assessed factors predictive of outcome. The median age was 59 years (36-72). Most patients (72%) were JAK2+ and had int2-high DIPSS (92%). The conditioning regimen consisted of thiotepa, busulfan , fludarabine (TBF). All pts received thiotepa 10 mg/kg and fludarabine 150 mg/m^2. The dose of busulfan was adjusted considering the age and the comorbidity score. One pt received 3 days of busulfan (total dose 9.6 mg/kg); 47 received 2 days (total dose 6.4 mg/kg) and 8 received one day of busulfan iv (3.2 mg/kg). Donor was an identical sibling in 13 pt, haploidentical in 18, matched unrelated donor (UD) in 18 and a mismatchedUD in 7. Thus we had 31 HLA matched and 25 HLA mismatched grafts. Fortytwo patients received post-transplant cyclophosphamide (PTCy)-based GVHD (Graft versus host disease ) prophylaxis with cyclosporine and mycophenolate mofetil , and 14 patients received a standard GvHD prophylaxis (CSA+MTX+ATG). The 2 year survival (OS) was 73 % and disease free survival (DFS) was 66 % and the cumulative incidence (CI) of TRM was 23% and of relapse 11%. The incidence of acute GvHD grade II-IV was 22% in HLA matched and 50% in HLA mismatched pts (p=0.022), grade III-IV was 6% and 25% respectively (p=0.042) . The incidence of moderate-severe chronic GvHD was 25% in HLA matched and 36% in HLA mismatched grafts (p=0.36). HLA had a major impact on survival : 85% vs 49% survival for matched vs mismatched patients (p=0.01). Patients age >60 years had a major impact on outcome, with a 2 year survival of 51% vs 88% in patients over (n=24) or under 60 years of age (n=32) (p=0.007; the DFS was 46 % and 80% respectively and the CI of TRM was 42% vs 9% (p=0.003). As to the total dose of busulfan, we found 26% TRM in patients receiving busulfan for 2 days (total doe 6.4 mg/kg) (n=47) and 0% in older patients receiving 1 day only (total dose 3.2 mg/kg) (n=8) ; relapse rate was 10% and 20% respectively. In multivariate cox analysis including age, spleen size ,DIPSS score, number of transfusion received and donor type, only HLA matching influenced the incidence of acute GvHD; transfusion burden and age plays a role in NRM and OS; DIPSS predicts relapse . In conclusion: older patients with MF have a high NRM and need to be prepared with a milder conditioning regimen. Disclosures Laurenti: Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

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Allogeneic Hematopoietic Stem Cell Transplantation for Pesaro IIIβ-Thalassemia Major Using Fludarabine-Based Myeloablative or Non-Myeloablative Conditioning Regimen.

Blood ◽

10.1182/blood.v106.11.3822.3822 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3822-3822

Author(s):

Kanger Zhu ◽

Jian Gu ◽

Tao Zhang ◽

Juan Zhong

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conditioning Regimen ◽

Thalassemia Major ◽

Organ Damage ◽

Unrelated Donor ◽

Myeloablative Conditioning ◽

Peripheral Blood Stem Cells ◽

Hematopoietic Stem

Abstract Objective : To explore the efficacy of Fludarabine-based myeloablative or non-myeloablative conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for classIII thalassemia major with regard to regimen toxicity, graft rejection, and disease-free survival (DFS). Methods: From June 2001 to October 2004, 8 patients underwent allo-HSCT in our BMT unit, including 5 male and 3 female, with median age 5 (3 ~ 19) years. Four patients received graft from sibling donor, including cord blood and peripheral blood stem cells, and the remaining 4 patients received graft from unrelated donors, including bone marrow and peripheral blood stem cells. Fludarabine (FDR) was added into the standard BU/CY regimen, consisting of FDR, BU, CY and ATG. Six patients received myeloablative stem cell transplantation and the remaining 2 patients with evidence of organ damage from iron-overload received nonmyeloablative unrelated donor stem cell transplantation. All patients received Cyclosporine A and Methotrexate for GVHD prophylaxis. Results: Eight patients were successfully engrafted with the median time of absolute neutrophil count (ANC) more than 0.5 ×109 /L was day +13 (+9 ~ +14), and the median time of platelet count more than 20 ×109 /L was day +25 (+8 ~ +39). Two patients died of grade IV aGVHD. The regimen-related toxicity (gradeImucositis, gradeII hemorrhagic cystitis, and gradeIhepatic toxicity) occurred in 3 patients. At a median follow up of 24 (8~48) months, the probability of DFS was 75%, including the two patients given nonmyeloablative stem cell transplantation from unrelated donor. Conclusion: Fludarabine-based conditioning regimen for allo-HSCT in Pesaro III thalassemia major was well tolerated, without increasing toxicity, and associated with durable engraftment and higher rate of DFS (75%). The successful transplantation from unrelated donors using nonmyeloablative conditioning showed that thalassemia clone can be eradicated by the reduced intensity HSCT, which relies upon immunosuppressive rather than myeloablative conditioning to facilitate engraftment of donor cells, and is a novel approach for the treatment of the patients with evidence of organ damage from iron-overload.

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Monosomal Karyotype in Myeloid Malignancies Is Prognostically Worse Even After Allogeneic Hematopoietc Stem Cell Transplantaion; Results From Two Transplant Centers,

Blood ◽

10.1182/blood.v118.21.4154.4154 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4154-4154 ◽

Cited By ~ 1

Author(s):

Minauchi Koichiro ◽

Akio Shigematsu ◽

Masanobu Nakata ◽

Toshihiro Matsukawa ◽

Koh Ebata ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cox Regression ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Structural Abnormality ◽

Hematopoietic Stem ◽

Myeloid Malignancies ◽

Monosomal Karyotype

Abstract Abstract 4154 Background: Monosomal karyotype (MK) has been defined as the presence of two or more autosomal monosomies or of a single monosomy associated with at least one structural abnormality (Breems et al, JCO 2008). The presence of MK has been associated with extremely poor prognosis in patients with not only acute myeloid leukemia (AML) but myelodysplastic syndrome (MDS) (Patnaik et al, Leukemia 2011). Our goal was to investigate the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for myeloid malignancies with MK. Patients and methods: We combined data from two transplant centers, Sapporo Hokuyu Hospital and Hokkaido University Hospital, and analyzed consecutive patients who underwent allogeneic transplantation for AML and MDS between January 2003 and July 2010. Patients were divided according to MK classification scheme into four groups (Oran et al, BBMT 2011), CN; cytogenetically normal, MK; monosomal karyotype, CBF; core binding factor abnormalities, Oth (Others); non-CBF and non-MK abnormalities. Patients with acute promyelocytic leukemia were excluded. Resuts: One-hundred eighty three out of 229 patients were analyzed with a median age of 48 years(15–68). Sixty one (33%) were from HLA-matched related donors, 86 (47%) from unrelated and 36 (20%) were cord blood.Conditioning regimens were myeloablative (MAC, n=102, 56%) or reduced intensity(RIC, n=81, 44%). Seventy patients (38%) were cytogenetically normal, 27 (15%)had CBF abnormalities, 70(38%) had non-CBF and non-MK abnormalities and 16(9%) had monosomal karyotype. There was no statistically difference between four groups in age, donor source and conditioning regimen. In the MK group, the proportion of MDS and non-remission state at stem cell transplantation were significantly higher than other groups (p=0.002, p<0.001). Four-year over all survival in patients with MK was 0%, which was significantly inferior to other groups; 50% for CN, 30.4% for CBF, 29.4% for Oth(p<0.001). Cox regression modeling showed that the disease status at stem cell transplantation (p=0.026) and the existence of MK (p=0.012) had prognostic value. Seven of 16 patients with MK died within the first 50 days after transplantation, and 9 patients died within 120 days. Five patients died of infection and 2 died of complicated organ failure and 2 died of progression disease. Three patients who underwent transplantation at non-remission setting, survived more than 1-year experienced chronic graft-versus-host disease, suggesting the existence of GVL effect to myeloid malignancies with MK. Conclusion: This retrospective analysis revealed the dismal prognosis of myeloid malignancies with MK, even after allogeneic HSCT. Novel therapies and strategies are urgently needed for this very poor prognostic group. Disclosures: No relevant conflicts of interest to declare.

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