Relapse After Allogeneic Hematopoietic Stem Cell Transplantation in Hematological Malignancies: Factors Impacting Its Occurrence and Treatment Options for a Better Management,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4093-4093
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Helene Labussiere ◽  
Marie Y. Detrait ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Negative Impact ◽  
Treatment Options ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Abo Incompatibility ◽  
One Year

Abstract Abstract 4093 Introduction: Relapse remains a major cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological diseases. During the last decade, many improvements have been achieved in the understanding of the disease- and patient-related conditions in order to obtain the optimal allogeneic effect but the relapse is still representative which leaded to the development of different chemo- and immuno-therapy strategies. Aims: To evaluate at a first time the different pre- and post-transplantation factors impacting the relapse occurrence after allo-HSCT, and at a second time, to evaluate factors impact the survival post-relapse including the different treatment options. Material and methods: We have retrospectively studied the occurrence of relapse in 345 patients, 198 (57%) males and 147 (43%) females with a median age of 43 years (range17–66) who received allo-HSCT at our institution for hematological malignancies between years 2000 and 2011; 205 (59%) from siblings donors and 140 (41%) form unrelated donors. At transplantation, there were 148 (43%) patients in first complete response or first chronic phase (CR1/CP1), 66 (19%) in CR2/CP2 and 131 (38%) < CR2/CP2. Two hundred and six (60%) patients received a full intensity conditioning and 139 (40%) a reduced intensity one. The different patients and transplantations characteristics are detailed in Table 1. Results: After HSCT, 336 (97%) patients engrafted. The cumulative incidence of acute GVHD≥2 at 3 months was 35% (95%CI 32–37); the cumulative incidence of extensive and limited chronic GVHD at one year was the same 15% (95%CI 13–17). After a median follow-up of 11.4 months (range 4–129), the median overall survival (OS) for the whole population was 19 months (range 12–33) with a 2-years probability of 47% (95%CI 42–53). Eighty eight (25.5%) patients relapsed with a cumulative incidence at one and two years of 19% (95%CI 17–21) and 22% (95%CI 20–24) respectively. Characteristics of relapsed patients are described in Table 1. After relapse, 65 (74%) patients were treated [21 (32%) received donor lymphocyte infusion (DLI) alone, 21 (32%) chemotherapy alone, 14 (22%) DLI + chemotherapy and 9 (14%) received other treatment] and 23 (26%) were not treated due to deadly relapse. The median OS from relapse was 4 months (range 3–5) and the one year probability of OS in patients who relapsed was 21% (95%CI 14–31). The multivariate analysis studying the impact of different variables on the occurrence of relapse showed a negative impact of disease status [<CR/CP: HR=3.9 (2.4–6.7), p=0.0001], a negative impact of CMV status [D+R-: HR=2.4 [1.2–4.7], p=0.009] and a protective impact of cGVHD [HR=0.37 (0.2–0.6), p=0.0002]. The multivariate analysis studying the pre- and post-relapse variables on the survival after relapse showed a positive impact of ABO incompatibility [Major ABO incompatibility: HR=0.39 (0.16–0.9), p=0.03], a negative impact of disease status [<CR/CP: HR=2.4 (1.3–4.4), p=0.003] and a positive survival outcome in patients receiving DLI with or without chemotherapy [HR=0.5 (0.3–0.8), p=0.005]. Conclusion: We showed that relapse after allo-HSCT in hematological malignancies is still a significant issue, disease status at HSCT and CMV matching worsen its occurrence while cGVHD can be protective. Survival rate after relapse is still very low reflecting the difficulty to find an optimal treatment, disease status at transplantation seem to have a long term effect while the use of DLI with or without chemotherapy can offer better results. In addition to the new chemotherapy molecules, immunotherapy should be used in order to enhance the graft-versus-leukemia effect not only after relapse, but also early in presence of a minimal residual disease. Disclosures: No relevant conflicts of interest to declare.

Is the Use of 9/10 HLA Unrelated Donors Still Acceptable in Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies? Comparison with Transplants From 10/10 HLA Unrelated Donors and Siblings

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3087-3087
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Marie Y. Detrait ◽  
Helene Labussiere ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
One Year

Abstract Abstract 3087 Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only potential to cure wide types of hematological diseases. A patient has 30% of chance to find a HLA-identical sibling donor while the rest of patients should find an alternative unrelated donor. The use of 10/10 HLA matched unrelated transplants has been used as a main alternative and with its unavailability, when available, a 9/10 HLA mismatched unrelated transplant has been used. The outcome of this last mismatched transplant is not very clear and its use according to patient and disease conditions has not been well defined yet. Aims To evaluate the outcome of allo-HSCT from 9/10 HLA mismatched unrelated donors compared to those from 10/10 HLA identical unrelated donors and siblings; and to define which category of patients can benefit the more in each alternative. Material and methods We have retrospectively studied the outcome of 213 patients who received allo-HSCT for different hematological malignancies, 121 (57%) from HLA identical siblings, 63 (29%) from 10/10 HLA identical unrelated donors and 29 (14%) from 9/10 HLA mismatched unrelated donors treated during the same period of time between 2006 and 2011 at our institution. In the mismatched group, 12 patients had the mismatch at HLA-A locus, 7 at the HLA-B, 7 at the HLA-C and 3 at the HLA-DQ. Characteristics between the 3 groups were comparable except for: disease type between the 2 unrelated groups, sex-matching, CMV-matching and ABO-matching. The different characteristics are detailed in Table 1. Results After HSCT, engraftment was significantly lower in the 9/10 HLA group (90%) than in the 10/10 HLA group (95%) than in the sibling group (99%), (p=0.03); the cumulative incidence of acute GVHD ≥2 at 3 months was 32% (23–41), 20% (15–26) and 27% (23–32) respectively; the cumulative incidence of extensive chronic GVHD at one year was 21% (13–30), 9% (5–13) and 17% (14–21) for the 3 groups respectively. After a median follow-up of 8 months (0–54) in the 9/10 HLA group, 10 months (0–60) in the 10/10 HLA group and 18 months in the siblings group, the median overall survival (OS) was 10 months (5–21), 18 months (11-NR) and 60 months (31-NR) respectively with a 2-years probability of 19% (8–44), 43% (31–59) and 63% (54–74) respectively. There was a higher but not significant relapse incidence at one year in the 9/10 HLA group compared to other groups while the transplant related mortality was significantly higher with a cumulative incidence at 1 year of 45% (35–55), (p<0.001) (Table1-results). In multivariate analysis, OS was negatively affected by unrelated donors [9/10 HR=5 (2.7–10), p=0.0001; 10/10 HR=2 (1.2–4), p=0.01], female donors [HR=2 (1.4–4), p=0.03] and disease status < CR1 or <chronic phase (CP) 1 [HR=3 (1.4–6), p=0.003]; while the TRM was negatively affected by unrelated donors [9/10 HR=9 (4–20), p<0.001; 10/10 HR=4 (1.2–10), p=0.03], female donors [HR=3 (1.2–7); p=0.01] and ABO minor incompatibility [HR=2.5 (1.2–5), p=0.01]. The funnel plot showing the adjusted TRM according to all covariates and comparing to the global population death rate, shows that the 9/10 HLA group has the worse TRM independently of any other factor. Conclusion We showed that allo-HSCT from 9/10 HLA mismatched unrelated donors have a significantly worse OS than those from matched unrelated donors and siblings; this was mainly due to an increased TRM in this group. Patients in first CR or CP could benefit the more from matched or 9/10 unrelated allo-HSCT while the use of transplants from 9/10 HLA unrelated donors in patients not in CR1 or CP1 should be limited to clinical trials. In view of these results, we should consider and evaluate the use of cord blood as an alternative source of transplant according to patient and disease conditions. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Excellent Outcomes of the Second Allogeneic Hematopoietic Stem Cell Transplantation in Hematological Malignancies with Reduced Toxicity Conditioning and Donor Change

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4891-4891
Author(s):  
Yongqiang Zhao ◽  
Yanzhi Song ◽  
Zhihui Li ◽  
Fan Yang ◽  
Feifei Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Relapse Rate ◽  
Tp53 Mutation ◽  
Hematological Malignancies ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
One Year ◽  
Reduced Toxicity

Abstract Introduction: High relapse rate and transplant-related mortality (TRM) are the major obstacles for the second allogeneic hematopoietic stem cell transplantation (allo-HSCT). Reduced-toxicity conditioning (RTC) can decrease TRM and healthier donor may provide stronger anti-leukemia and anti-infection effects. Objective:In current clinical study, the safety and efficacy of the second allo-HSCT with RTC and donor change were examined. Methods: Between April 2018 and June 2021, total 48 patients with hematological malignancies (B-ALL 26, T-ALL/LBL 4,AML16,MDS 2) who failed to the first allo-HSCT(relapsed 47, secondary rejection 1) and underwent the second allo-HSCT in our hospital were enrolled. The median age was 25(5-55) years old. Male to female was 25:23. Before the second allo-HSCT, 35 (72.9%) patients were in complete remission (CR) (minimal residual disease (MRD) negative in 28, MRD positive in 7), and 13 (27.1%) cases (B-ALL7,T-ALL/LBL2,AML3,MDS1) in non-remission(NR). The median interval between twoallo-HSCTs was 19.5 (8-77) months. For better donor selection, the functions of hematopoiesis and immune (subsets of lymphocyte, immune globulin,and granzyme and perforin of NK cell) as well as hematological and immunological hereditary predisposition gene variants for potential donors were tested. The types of the first allo-HSCT included haploidentical (n=33), unrelated (n=8), identical sibling (n=5), and unrelated cord blood (n=2). All donors were changed for the second allo-HSCT(haploidentical 35, unrelated 13)except one recipient no other donor available. RTC regimens were mainly total body irradiation(TBI)/fludarabine (FLU)-based(n=39) or busulfan (BU)/FLU-based (n=7).Two patients were with total marrow irradiation (TMI)/FLU-basedregimen. For TBI/FLU regimen, fractionated TBI (8Gy in 32, 10Gy in 7), cytarabine 1-2g/m 2 for 3 days,FLU 30mg/m 2 for 5 days, Me-CCNU 250mg/m 2 for 1 day, and ATG were used. For BU/FLU regimen, BU 0.8mg/kg q6h for 3 days, cytarabine 1-2g/m 2 for 3 days,FLU 30mg/m 2 for 5 days, Me-CCNU 250mg/m 2 for 1 day, and ATG were used. For TMI/FLU regimen, the same conditioning as TBI/FLU was used except fractionated TMI 10-12Gy instead of TBI. Decitabine (20mg/m 2, 3 days) or etoposide (200mg/m 2, 2 days) were administrated in some patients in NR or MRD positive. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for graft-versus-host disease (GVHD) prophylaxis. Some patients received maintenance therapy post-transplant with targeted medicine based on their fusion genes or gene mutations. Results: ALL patients became full donor chimerism. The median time for neutrophil and platelet recovery was 15 (11-22) days and 16 (10-240) days. The incidences of grade II-IV acute GVHD (aGVHD) and chronic GVHD(cGVHD) were 18.8%, 47.5% (limited 25%, extensive 22.5%), respectively. The incidences of CMV and EBV reactivation were 31.3% and 6.3%. No severe hemorrhagic cystitis occurred. The median follow-up was 13(1-38) months. One-year disease-free survival (DFS) and overall survival (OS) of all patients were 68.7% (95% CI:0.511;0.811) and 78.9% (95% CI:0.62;0.889) . Nine patients died(relapse 7,GVHD and infection 2).The relapse rate was 22.9%.TRM was only 4.2%. NR before transplant and TP53 mutation were high risk for disease recurrence post-HSCT. Relapse rates were 53.8% vs. 11.4% in NR and CR patients, and 50% vs. 17.5% in the patients with or without TP53 mutation. Disease status before transplant was key impact factor for survival after the second allo-HSCT. One-year OS in CR and NR settings were81.4 % and 70%, respectively, p=0.13. One-year DFS in CR and NR settingswere79.6%, and 41.9%, respectively, p=0.005. No significant difference of DFS was seen in haploidentical and unrelated transplants(68.1% vs.71.8%, p=0.627). Conclusions: With our strategy of RTC regimens and donor change, excellent outcomes of the second allo-HSCT in hematological malignancies have been achieved. One-year DFS and OS are 68.7% and 78.9%. Both TRM and relapse rate are low (4.2%, 22.9%). The most important factor on prognosis of the second allo-HSCT is disease status before transplant but not donor type. TP53 mutation also has negative impact on DFS after the second allo-HSCT. Disclosures No relevant conflicts of interest to declare.

Haploidentical Hematopoietic Stem Cell Transplantation of Sex-Matched Donor-Recipient Pair Has Survival Advantage: A Single-Center Study of 440 Cases

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 228-228 ◽  
Author(s):  
Tong Wu ◽  
Yan-Li Zhao ◽  
Jing-Bo Wang ◽  
Xing-Yu Cao ◽  
Yu-Ming Yin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematological Malignancies ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Male Donor ◽  
Female Donor ◽  
Matched Donor

Abstract Abstract 228 Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an important alternative option for patients with hematological malignancies who need urgent transplant but without HLA matched either sibling or unrelated donor (Dao-Pei Lu et al., Blood 2006; 107:3065). Each patient usually has several haploidentical family members who could be selected as a donor. To determine the principal of donor selection among all available related haploidentical candidates, the clinical outcomes of a large series of haplo-HSCT in our hospital are analyzed. From April 2002 to April 2010, consecutive 440 patients with hematological malignancies who underwent haplo-HSCT were included. The median age of patients was 23 (3-59) years old. The diagnosis included AML (39.8%), ALL (35.9%), MDS (3.6%), CML (16.1%), and others (4.6%). Transplants at CR1 or CML-CP1, ≥CR2 or CML-CP2/AP, and advanced disease (refractory/relapsed acute leukemia or CML-BC) were 33.4%, 40.9% and 25.7%. HLA mismatched at 1, 2, 3 loci was 13.2 %, 27.5%, 59.3%, respectively. Transplants in sex-matched donor-recipient pair, female donor to male recipient, and male donor to female recipient were 55.1%, 33.0% and 13.9%. Major clinical characteristics among these three arms were similar. All patients received unmanipulated combined marrow and peripheral blood stem cells for transplant after BUCy2/CyTBI plus ATG conditioning. Fludarabine was substituted for cyclophosphamide in some patients due to impaired organ function. Prophylaxis and treatment of GVHD were reported previously. Steady hematopoietic reconstitution was seen in 98.6% of recipients. The cumulative incidences of grade II to IV acute GVHD and chronic GVHD were 32.6%, 61.3%, respectively. 100-day mortality was 10.5%. With the median follow-up of 32 (3-99) months, 2-year and 5-year overall survival (OS) rates for patients who were in different disease status were 57.9% and 52.9%. Univariate and multivariate analysis all showed that disease status before transplant, CD34+ cell dosage infused and sex-matched or not between donor and recipient but not HLA disparity and age were pivotal impact factors on survival. Two-year OS of transplants in sex-matched donor-recipient pair, female donor to male recipient, male donor to female recipient were 65.5%, 55.3%, 37.6, respectively (p=0.000). No significant differences were found on OS of transplants among haploidentical donors from sibling or parent or offspring or other relatives. In conclusion, our clinical results from a large series of transplants demonstrate that haplo-HSCT in sex-matched donor-recipient pair has survival advantage. Therefore, in haplo-HSCT, sex-matched donor should be the first choice, if not available, then female donor to male recipient could be the second option. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Cellular Therapy with Haploidentical Peripheral Hematopoietic STEM CELL Transplantation MAY be a Therapeutic Option in Patients with Relapsed Lymphoma with Chemorefractory Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2189-2189
Author(s):  
Simona Sammassimo ◽  
Daniele Avenoso ◽  
Federica Gigli ◽  
Daniele Laszlo ◽  
Francesco Bertolini ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cumulative Incidence ◽  
Cellular Therapy ◽  
Disease Status ◽  
Haematological Malignancies ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Background: haploidentical hematopoietic stem cell transplant (HSCT) with post-transplant cyclophosphamide (Cy) is a procedure for patients with advanced haematological malignancies lacking an HLA identical donor. Even if several groups reported interesting results about allograft in lymphoma, the current clinical practice doesn't include routinely allogeneic stem cell transplantation in patients with suboptimal response to salvage strategies. A prospective study based on the use of peripheral blood stem cells (PBSC) as graft source was launched at European Institute of Oncology in 2010. The aim of this paper is to report the results of haplo-HSCT in patients with relapsed and refractory lymphoma with detectable disease before transplant. Patients and Methods: between June 2010 and May 2018, 64 have been enrolled in the study at our institute; the updated experience of 35 patients affected by high risk lymphomas is reported.Haploidentical HSCT was performed with G-CSF mobilized PBSC. Conditioning regimen was either non-myeloablative (31 patients) (Cy 14.5 mg/kg/die days -6,-5, fludarabine 30 mg/m2/die days -6 to -2, and 200 cGy Total Body Irradiation day -1), or myeloablative (treosulfane 14 mg/m2/die days -6 to -3 and fludarabine 30 mg/m2/die days -6 to -2). GVHD prophylaxis consisted of post-transplant cyclophosphamide (50 mg/kg day +3 and +4) and mycophenolate and tacrolimus as previously described.Among 35 evaluable patients, 28 (80%) performed haplo-HSCT for refractory/relapsed non-Hodgkin lymphoma; the remaining patients included 7 relapsed and refractory Hodgkin lymphoma. Median age was 52 (19-73), disease status included 13 (37%) complete remission (2 CR1, 11 CR≥2), 9 (26%) partial response (PR), 4 (11%) stable disease (SD), 9 (25%) progressive disease (PD). A median of 5.5 x106(range 2.45 -13.4) CD34+ cells/kg was infused, with a median of 2.8x108(range 0.3-5.4) CD3+ cells/kg. Median lines of previous treatment: 3 (0-7). Results: four deaths due to infections have been recorded before engraftment. Among all 64 evaluable patients, median time to absolute neutrophils ≥500/µL was 18 days (range 12-29), and 23 days (range 11-65) to platelets ≥20.000/µL. Incidence of grade I-II acute GVHD was 22%, with grade III of 2%. Mild chronic GvHD was observed in 7/60 evaluable patients (1-year cumulative incidence: 13 %). Mixed donor chimerism was achieved in all 60 evaluable patients, with CD3+ chimerism >50% at day +28, >90% at day + 84. No graft failure has been recorded. CMV reactivation occurred in 77% of lymphoma patients (27/35 subjects at risk), at a median of 35 days (range 5-50) post-HSCT; pre-emptive therapy was effective in all patients. Regarding the lymphoma population, with a median follow-up of 360 days (6-2,460), 19 patients are alive (54%), 18 of them (51% of the whole series) in CR, while the cumulative incidence of relapse is 25%; when disease status at transplant is considered, the incidence of relapse at 2 years is 4% and 54% for chemo-sensitive and chemo-refractory, respectively (see graphic 2 in figure 1). Overall, 16 patients (45%) died; causes of death were PD in 8 patients (50%), infections in 8 (50%) with a cumulative transplant related mortality of 45%. The 3-year PFS and OS for the all lymphoma patients is 58% and 54%, respectively, with 81% and 66% for patients transplanted in CR/PR and 32 % and 31% for those transplanted in SD/PD (p-value 0,001 Log-rank - graphic 1 in figure 1). Conclusions: Haploidentical T-cell replete PBSC transplantation with high-dose post-transplant Cy is a feasible procedure for high-risk haematological malignancies, with an overall toxicity analogous to HSCT with HLA-identical donors. Despite the small study population, haplo-HSCT seems to be an effective strategy even in patients with active lymphoma before transplant. As previously reported, chemosensitive (CR/PR) patients have a better outcome compared to chemo-refractory cases. However, the latter population still may have a benefit from haplo-HSCT as suggested by our data, thus the cellular therapy strategy should not be discouraged in presence of disease (SD/PD). Our future purpose is to enhance the graft versus lymphoma effect with Natural Killer cells infusions. This option will be soon developed at our hospital within a prospective trial. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Hematopoietic Stem Cell Transplantation Phase III Clinical Trials for Patients with Hematological Malignancies in the US: Lessons To Be Learned from the European Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 229-229
Author(s):  
Sejal S. Kuthiala ◽  
Gary H. Lyman ◽  
Oscar F. Ballester
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematological Malignancies ◽  
Care Delivery ◽  
Physician Attitudes ◽  
Phase Iii ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
The Us

Introduction: Evidence-based medicine defines standard therapies primarily from Phase III randomized controlled trials (RCT), when available. In this report we examined trends in ther number and characteristics of phase III RCT addressing the management of adult patients with hematological malignancies, comparing the patterns of activity in the US and Europe. Materials and Methods: We attempted to identify all phase III RCT published in the English medical literature from 1/1992 to 12/2003. A systematic search of Medline and published references was conducted using multiple keywords for each malignancy as well as for hematopoeitic stem cell transplant (HSCT). We cross-referenced the data by searching individual journals, as well as the ASH education books from 1998–2003. Studies published in abstract form only were not included. Results: We identified 306 published RCT that accrued a total of 4899 patients. Eighty-three of these studies included HSCT with a total accrual of 2081 patients. Country of origin included: US (n= 25), Europe (n=54), other (n=4). Four European countries (France, Italy, Germany and UK: FIGU) with a combined population similar to that of the US produced 32 studies. This figure for FIGU does not include their contributions to 12 separate European cooperative trials. There were no significant trends in the number of trials published per year during the study period. However, significant differences emerged when the focus of the studies and the accrual numbers were analyzed. RCTs comparing HSCT to standard dose therapy represented 34.9% of the 83 trials and 59.4% of FIGU trials, but only 4% (1 out of 25) of US studies (p <.001). US trials accrued a mean of 110.2 patients per study, as compared to 205.3 in other countries and 222.6 in FIGU studies (p= .006). In multivariate analysis, only focus of study was independently related to greater study size (p<.001). Among the remaining 223 trials not involving HSCT (US produced 68 and FIGU 77), a significant trend for increasing numbers of trials published per year during the study period was documented (p=.015). No significant differences in the mean number of patients accrued per trial (US= 279.5, other countries= 302.8 and FIGU= 347.8), or in the focus of the studies were observed in univariate or multivariate analysis. Conclusions: While there has been an increase in the number of Phase III RTCs in patients with hematological malignancies published during 1992–2003, the activity for HSCT trials has remained stationary. US HSCT trials have focused on issues other than the comparison of HSCT to standard therapies, such as graft manipulation, growth factors and graft versus host disease. US HSCT have accrued significantly fewer patients per study. The reasons for these differences are not apparent from our data, and may include patient and/or physician attitudes/biases toward phase III trials, issues of financial coverage for the HSCT procedure and/or health care delivery policies. There is a serious paucity of US trials defining the role of HSCT in the management of hematological malignancies.

Clostridium Difficile Infections After Allogenic Hematopoietic Stem Cell Transplantation: Comparison of Cord Blood to Other Grafts

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4573-4573
Author(s):  
Kohei Hosokawa ◽  
Masanori Tsuji ◽  
Hideki Araoka ◽  
Kazuya Ishiwata ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Clostridium Difficile ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Cumulative Incidence ◽  
Hematopoietic Stem

Abstract Abstract 4573 Background: Clostridium difficile, a gram-positive sprore-forming anaerobic bacillus, associated diarrhea (CDAD) is a major cause of nosocomial antibiotic-associated diarrhea. Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of developing CDAD during the early posttransplant period due to prolonged exposure to broad-spectrum antibiotics and immunosuppressive agents. The incidence of CDAD has been increasing up to as high as 20% in allogeneic bone marrow (BMT) and peripheral blood stem cell transplantation (PBSCT). Although cord blood transplant (CBT) recipients are subjected to delayed immune constitution and high incidence of infectious complications to be risk factors for CDAD, the frequency of CDAD after CBT is unclear. We therefore retrospectively investigated the incidence and clinical features of CDAD in patients receiving CBT. Objectives/Methods: During the 2-yr retrospective period (2007–2008), 201 allogeneic HSCT were performed at the Department of Hematology of Toranomon Hospital: 135 CBT, 39 BMT and 27 PBSCT. The median age of the patients was 56 yr (range, 19–82 yr). All patients with diarrhea had a minimum of one diarrheal stool sample evaluated for the presence of toxin A. A patient found to have toxigenic Clostridium difficile by ELISA was diagnosed as CDAD. The cumulative incidence of CDAD was calculated using the Gray method considering death without CDAD as a competing risk. Overall survival (OS) was estimated by the Kaplan-Meier method. The time-dependent Fine and Gray proportional hazards model was used for multivariate analysis. Results: CDAD developed within 100 days in 11 out of 135 CBT recipients at a median onset of day 18 (range, 3–56 days). The cumulative incidence of CDAD after CBT was 9% at day 100 (Fig 1), which was similar to that after BMT (6%, P= 0.55) and to that after PBSCT (16%, P=0.27). All 17 patients who developed CDAD were successfully treated with using oral metronidazole or oral vancomysin. Of the 17 patients with CDAD, 7 (41%) died within 100 days after transplant, and the direct cause of death was irrelevant to CDAD in the 7 patients. The 1-yr survival after diagnosis of CDAD was 58%, which was comparable to that in patients without developing CDAD (59%, P=0.98). The univariate analysis failed to identify any significant risk factors for CDAD as well as the multivariate analysis. Conclusions: The current study showed that CDAD developed early after CBT at the incidence similar to BMT or PBSCT, and that prompt treatment for CDAD may work in improving its prognosis. It is therefore essential to recognize CDAD as one of the differential diagnosis of diarrhea because it is treatable complication after HSCT. Disclosures: No relevant conflicts of interest to declare.

The Clinical Significance Of Diastolic Dysfunction On The Outcome After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4550-4550
Author(s):  
Naoki Shingai ◽  
Kazuhiko Kakihana ◽  
Shuntaro Ikegawa ◽  
Yukie Takahashi ◽  
Jun Aoki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Diastolic Dysfunction ◽  
Disease Status ◽  
Cardiac Complications ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Hla Compatibility

Introduction Cardiac diastolic dysfunction plays a crucial role in the development of heart failure. The ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e') reflects left ventricular end-diastolic pressure and is used in the diagnosis of diastolic heart failure. Although cardiac complication is one of the most serious problems in hematopoietic stem cell transplantation (HSCT), the impact of diastolic dysfunction on clinical outcomes after allogeneic HSCT is unclear. Thus, we investigated the effects of diastolic dysfunction on HSCT using E/e'. Patients and Methods We retrospectively reviewed the records of 102 evaluable patients who underwent their first allogeneic HSCT at our hospital between November 2010 and July 2012, and investigated whether elevated E/e' would affect the clinical outcomes such as incidence of cardiac complications, overall survival (OS) and non-relapse mortality (NRM). Patients were classified into high- E/e' group if E/e' was ≥9 and classified into low- E/e' group if E/e' was <9. In multivariable analysis, the hazard ratio of E/e' was adjusted for variables with a P -value ≤ 0.2 in a univariable analysis, with stepwise deletions. Results This study analyzed 58 males and 44 females with a median age of 47 years (range: 15-71). Forty one patients were classified into the high- E/e' group and 61 classified into the low- E/e' group. High- E/e' patients were older than low- E/e' patients (median: 57 years in E/e'-high vs. 41 years in E/e'-low, P=0.027). Reduced intensity regimen was more frequent in the high- E/e' group (39% vs. 16%, P=0.019) and there were also more men in the high- E/e' group compared with patients in the low- E/e' group (68% vs. 49%, P=0.07). Twelve patients developed cardiac complications during the first 100 days after HSCT (Day100) and its cumulative incidence was11.9%. Of them, 6 patients developed heart failure, 5 developed arrhythmia, and 1 developed both myocardial ischemia and heart failure. The cumulative incidence of cardiac complications at Day 100 was significantly higher in the high- E/e' group (22.4%) than that in the low- E/e' group (22.4% vs. 5%, P=0.0087, Figure 1a). Non-relapse death occurred in 17 patients within 1 year after HSCT. Nine patients died of infection, 3 died of hemorrhage, 2 died of graft-versus-host disease, 1 died of heart failure, 1 died of thrombotic microangiopathy, and 1 died of veno-occlusive disease/sinusoidal obstruction disease. NRM was higher in the high- E/e' group than in the low- E/e' group (28.8% vs. 10.5% at 1year, P=0.0165, Figure 1b). A multivariate analysis revealed that high- E/e' and high disease status were significant risk factors for high NRM (other co-variates were HLA compatibility and HCT-CI). Conversely, the relapse rate did not significantly differ in both groups (23% in the high- E/e' vs. 17% in the low- E/e' at 1 year, P=0.44). The OS was significantly poorer in the high- E/e' group than in the low- E/e' group (55.2% vs. 75.6% at 1 year, P=0.0085, Figure 1c). On multivariate analysis, E/e', disease status, and donor source were defined as independent prognostic factors for OS (other co-variates were HLA compatibility, preparative regimens, disease status, and QTc). Conclusions Diastolic dysfunction is associated with iron overload, anemia, diabetes, kidney disease, heart failure, cardiomyopathy, aging, and hypertension. Thus, pre-transplat E/e' value might reflect the potential risk of these diseases in transplant candidates and be associated with poor outcomes. Our results suggest that pre-transplant E/e' value would be an early predictor of cardiac complications and survival after HSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effect of Graft Source on Alternative Unrelated Donor Reduced Intensity Conditioning Hematopoietic Stem Cell Transplantation in Adults with Acute Myeloid Leukaemia after: A Study from the SFGM-TC

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2541-2541
Author(s):  
Florent Malard ◽  
Noel Milpied ◽  
Didier Blaise ◽  
Patrice Chevallier ◽  
Mauricette Michallet ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Disease Status ◽  
Reduced Intensity Conditioning ◽  
Transplant Patients ◽  
Significant Difference ◽  
Reduced Intensity ◽  
Acute Myeloid

Abstract Background. Allogeneic stem cell transplantation (allo-SCT) is a well-established therapy for adult patients with acute myeloid leukemia (AML), however many patients will not have a suitable matched sibling donor. The use of alternative stem cell sources has been investigated, especially the use of unrelated umbilical cord blood cells. Previous studies found a similar outcome between HLA 4-6/6 matched UCB, 7/8 mismatched unrelated donors (URD) and 8/8 matched URD. However, it is more common practice in many centers worldwide to search for 10/10 or 9/10 URD. Patients and methods. This retrospective analysis assessed the outcome of 651 patients over 18 years at time of transplant with an AML who received a reduced intensity conditioning (RIC) or non myeloablative conditioning (NMA) allo-SCT from UCB (n=205) or G-CSF mobilized peripheral blood stem cell (PBSC) 9/10 URD (n=99) or 10/10 URD (n=347) between 2002 and 2010 and who were reported to the registry Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). AML cytogenetic risk was favorable in 77 patients, intermediate in 373 and high risk in 113 cases; and unknown in 88 patients. Cytogenetic risk groups were comparable between all three subsets of patients. At time of transplant, patients’ median age was 55 years (19-70), 540 patients (83%) were in CR and 97 (17%) were in relapse/progression. In UCB, 99 patients received a single UCB unit and 106 patients received 2 UCB units. We analyzed engraftment, NRM, relapse/progression, GVHD, LFS and OS using the cumulative incidence procedure and Kaplan-Meyer estimates and multivariate Cox regression modeling. The most important parameters associated with outcome were analyzed and we included in the final multivariate analysis, along with graft source, parameters with a p value over 0.20 (patients age, disease status at transplant, cytogenetic risk, use of ATG, use of TBI, CMV status and conditioning regimen (RIC versus NMA)). Results. With a median follow-up of 43, 43 and 49 months in the 10/10 URD, 9/10 URD and UCB, hematopoietic recovery was slower in UCB compared to URD recipient: the cumulative incidence of neutrophils recovery at day 28 and platelet recovery >50×109/L at day 180 were respectively 76% and 68% in UCB against 95% and 91% in 10/10 URD and 93% and 81% in 9/10 URD (P<0.0001). While there was no significant difference in the day 100 cumulative incidence of grade 2-4 aGVHD: 32% in 10/10 URD, 39% in 9/10 URD and 33% in UCB, the 2 years cumulative incidence of cGVHD was significantly lower in UCB recipients: 16% against 37% in 10/10 URD (p<0.0001) and 29% in 9/10 URD (P=0.004). In multivariate analysis, the cumulative incidence of NRM was significantly lower in UCB recipients compared to 9/10 recipients (HR 1.83, P=0.03), there was no statistically significant difference with 10/10 recipients (HR 1.35, P=0.25). In multivariate analysis, the cumulative incidence of relapse/progression was significantly increased in UCB recipients compared to 10/10 URD recipients (HR 0.64, P=0.04) and there was also a trend towards an increased incidence of relapse compared to the 9/10 URD recipients (HR 0.62, P=0.07). Compared to UCB transplants there was no significant difference in LFS after 9/10 URD (HR 1.17, P=0.33) and 10/10 URD (HR 1.09, P=0.51). For OS, there was no significant difference between the 9/10 URD group and UCB transplants (HR 0.98, P=0.90), but there was a trend toward a better OS in the 10/10 URD group (HR 0.74, P=0.08). In multivariate analysis, relapse/progression risk was greater and LFS was lower in patients with intermediate or adverse risk cytogenetic and in patients who were not in CR at time of transplantation. Disease status at transplant (patients not in CR versus CR) was the only parameter with a significant impact on OS in multivariate analysis (HR 3.2, P<0.0001). Conclusion. These data suggest that UCB is a valid alternative graft source compared to 9/10 URD in patients who lack a 10/10 URD. The increased incidence of relapse/progression in UCB transplant was counterbalance by a decreased NRM incidence. Furthermore this study highlighted the significantly lower cumulative incidence of cGVHD in UCB transplant recipients, an important factor for patients’ quality of life after transplant. This should encourage us to pursue our effort to use UCB RIC/NMA allo-SCT with the development of new strategies to prevent relapse after transplant. Disclosures No relevant conflicts of interest to declare.

Risk Factor of Hepatic Veno-Occlusive Disease: Analysis of Clinical Data of 5024 Patients Extracted from the Database of the Japan Marrow Donor Program.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2970-2970
Author(s):  
Miwa Sakai ◽  
Kazuteru Ohashi ◽  
Takuya Yamashita ◽  
Hideki Akiyama ◽  
Hisashi Sakamaki
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Clinical Data ◽  
Univariate Analysis ◽  
Disease Status ◽  
Occlusive Disease ◽  
Blood Type ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Hepatic veno-occlusive disease (VOD) is one of the most serious complication of hematopoietic stem cell transplantation (HSCT). Various factors have been identified as increasing the risk of hepatic VOD, but few of them have been associated with a significantly increased risk. We retrospectively analyzed the clinical data of 5024 transplant recipients (median age28, range 0–68) which extracted from the Japan Marrow Donar Program. The diagnosis of VOD was made according to the McDonald’s criteria, and 324 out of 4833 patients (6.7%) were eventually diagnosed with VOD. The possible risk factors based on the previous studies were counted on an initial univariate analysis, and cumulated significant factors were further analyzed for their potential value for VOD development in multivariate analysis. Variables correlated with an increased risk of VOD were: time of transplant >2 times (relative risk (RR) 2.7; p=0.006), pretransplant disease status (RR 2.3; p=0.000), prior liver disease (RR 2.1; p=0.017), ABO blood type mismatch (RR1.7; p=0.000). In patients receiving either busulfan or melphalan for conditioning increased VOD risk (RR 1.5 and 1.8; p=0.007 and 0.002, respectively). In our multivariate analysis, stem cell source, and prophylactic use of heparin and Ursodiol had no significant effect on VOD development. This analysis might contribute to revise the previously reported risk factors for VOD and the data could be used to know which patients might be suitable subjects for new trials for VOD prevention.

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