The Clinical Significance of Matching for Alleles at the Low Expression HLA Loci DP, DQ and DRB3/4/5 in Unrelated Hematopoietic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 561-561 ◽  
Author(s):  
Marcelo Fernandez-Vina ◽  
John Klein ◽  
Michael D Haagenson ◽  
Stephen R Spellman ◽  
Stephanie J. Lee ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Hla Class I ◽  
Cell Types ◽  
Hematopoietic Stem ◽  
Minimal Impact ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Conditioning Regimens ◽  
The Difference

Abstract Single or multiple mismatches at HLA-A, B, C, and DRB1 have a detrimental effect on outcome of bone marrow transplantation using unrelated donors. Most of these loci encode for products that are expressed with high density on the surface of many cell types. In contrast, HLA-DRB3, DRB4, DRB5, DQ, DP encode for class II products that are expressed at low levels (LEL); some investigations suggest that mismatches in some of these loci have a minimal impact on outcome. We hypothesized that the influence of the LEL is weak and cumulative and only demonstrable in combination with mismatches (MM) in other loci. National Marrow Donor Program data from 3853 US transplants performed from 1988–2003 were analyzed to investigate this hypothesis. Patients had AML, ALL, CML or MDS and received myeloablative conditioning regimens. Most patients received calcineurin-based GvHD prophylaxis with T-replete grafts (79%). Nearly all received marrow grafts (94%). Median follow-up was 6 years. HLA loci were typed retrospectively by high resolution methods. MM was defined as the difference in the antigen recognition site of the HLA molecule of the patient and donor and computed in GvH and HvG vector, the highest vector mismatch was assigned as overall mismatch for a locus. Because multiple comparisons were made, only p-values <0.01 were considered significant. All analyses were adjusted for patient and transplant characteristics. Transplants were stratified according to match grade in the high expression loci (HEL) as 8/8, 7/8 and <7/8; the MM in LEL were computed as 0, 1, 2 and 3 or more MM. A greater degree of mismatch in the HEL was associated with a greater degree of MM in the LEL (p<0.0001); 3 or more MM in the LEL were found in 6, 11 and 21 percent of the patients receiving transplants matched in 8/8, 7/8 and <7/8 HEL groups, respectively. In the 7/8 group, multiple mismatches in the LEL loci were significantly more common in the patients presenting a mismatch in HLA-DRB1 than in the HLA class I loci (p <0.0001); 3 or more MM in the LEL loci were found in 33 percent of the patients presenting one mismatch in HLA-DRB1 while only 8 percent of the patients with one mismatch in either HLA-A, B or C loci presented 3 or more MM in the LEL loci. RESULTS: In the 8/8 HEL group, mismatches in LEL did not significantly associate with mortality. In the 7/8 HEL group, patients with 3 or more MM in LEL in the GvH vector had a significantly higher risk for mortality and treatment related mortality than the subgroups with 0MM (RR=1.44; 95% Confidence Interval (CI):1.07–1.94; p=0.015; and RR=1.63; CI:1.17–2.28; p=0.004) and 1MM (RR=1.46; CI:1.12–1.90; p=0.005; and RR=1.50; CI:1.12–2.01; p=0.006) in LEL, and a similar but not significant trend was observed when compared to the 2MM subgroup. No single LEL appeared to have a more pronounced effect on clinical outcome, when mismatched, versus the other LEL. CONCLUSION: The presence of 3 or more mismatches at LEL may adversely affect clinical outcome after 7/8 matched transplantation. Mismatches at HLA-DRB1 were associated with the occurrence of additional LEL mismatches. Prospective evaluation of matching for HLA-DRB3, 4, 5, DQ and DP loci may be warranted to reduce post-transplant risks in donor recipient pairs matched for 7/8 HEL.

Administration of Rituximab 375 Mg/m2 on Days +1 and +8 after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT) Regimens for Patients with Advanced CD20+ Lymphoid Malignancies

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4323-4323
Author(s):  
Mohamed A Kharfan-Dabaja ◽  
Cheryl Tate ◽  
Janelle Perkins ◽  
Teresa Field ◽  
Hugo F. Fernandez ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Response Rates ◽  
Hematopoietic Stem ◽  
Lymphoid Malignancies ◽  
Gvhd Prophylaxis ◽  
Mantle Cell ◽  
Conditioning Regimens ◽  
Nih Consensus Criteria ◽  
Time To Onset

Abstract We evaluated the safety of adding rituximab 375 mg/m2 only on days +1 and +8 following allo-HCT in 18 patients (M=12, F=6), median age 56 (41–66) years, with advanced CD20+ lymphoid malignancies [CLL=9 (CR2=3, PR2=3; ≥PR3=3); Mantle cell lymphoma (MCL)= 5 (CR1=1, PR2=2, ≥PR3=2); follicular (FL)=3 (CR3=2, ≥PR3=1); DLBC NHL=1 (≥PR3=1). Source of stem cells consisted of matched-related (MRD)=11 (61%), matched-unrelated (MUD)=5 (28%), or mismatched-unrelated (MMUD)=2 (11%) donors. Conditioning regimens consisted of fludarabine plus targeted doses of IV busulfan (FLU-BU) (N=11) or 200 cGy TBI (N=4), or cyclophosphamide (FLU-CY) (N=1). ATG was administered on days −3 and −1 in 2 MMUD cases (FLU-BU-ATG). Fifteen patients received rituximab on day +1 (±3) and all on day +8 (±3). GVHD prophylaxis was tacrolimus plus mycophenolate mofetil (N=11) or methotrexate (N=7). Non-relapse mortality at 100 days was 6%. Median time to neutrophils and platelets engraftment was 15 (6–27) days and 12.5 (9–18) days, respectively. Eight patients never dropped platelets below 20,000/uL. Median CD3 and CD33 chimerisms at day +90 (±10) were 89% (50%–100%) and 100% (15%–100%), respectively. DLI was required in 2 patients (FLU-BU=1, FLU-TBI=1) due to poor CD3 engraftment. Response rates after 90 days post allo-HCT, according to diagnosis, were as follows: CLL (evaluable=8/9; CR=7/8; PR=1/8); MCL (evaluable=4/5; CR=4/4); FL (CR=3/3); DLBC (PD=1/1). Twelve (67%) patients remain alive in remission at a median follow up of 9.4 (2.3–42.3) months. The incidence of grade 0,I, II, and III–IV acute GVHD (aGVHD) was 6%, 33%, 50%, and 11%, respectively. Time to onset of aGVHD was 29 (16–77) days. The incidence of chronic GVHD (cGVHD), per NIH consensus criteria, was as follows in 15 evaluable patients: no cGVHD= 27%, mild= 33%, moderate= 13%, and severe=27%. These findings suggest that administration of rituximab 375 mg/m2 only on days +1 and +8 is safe. Response rates are encouraging; but controlled studies will be needed to conclusively determine the effect of post-transplant rituximab on efficacy.

Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Survival for Patients with Chronic Myelomonocytic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4347-4347 ◽  
Author(s):  
Piyanuch Kongtim ◽  
Uday R. Popat ◽  
Antonio M. Jimenez ◽  
Sameh Gabella ◽  
Riad O. El Fakih ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Hypomethylating Agents ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Unrelated Donors ◽  
Conditioning Regimens

Abstract Introduction Allogeneic hematopoietic stem cell transplant (allo-SCT) is the only curative treatment modality for patients with CMML. Here we retrospectively reviewed the data for patients with CMML who received an all-SCT at our institution to identify factors associated with improved survival and determine whether treatment with hypomethylating agents (HMA) before transplant improves survival for these patients. Methods All 83 patients 18 years of age or older with a diagnosis of CMML confirmed at The University of Texas MD Anderson Cancer Center who underwent allo-SCT between April 1991 and December 2013 were identified through review of the institutionÕs medical records and included in this analysis. Forty, 7, and 36 patients had CMML-1, CMML-2 and CMML that had progressed to AML (CMML/AML) respectively. The median age was 57 years. CMML specific cytogenetic risk at diagnosis (Such E, hematologica, 2011) was good, intermediate, and high risk in 46, 19, and 18 patients respectively. Seventy-eight patients received induction treatment before transplant, 37 receiving HMA (either 5-azacytidine or decitabine) for at least 3 courses and 41 receiving 1-2 courses of cytotoxic chemotherapy. Among the patients who received induction therapy, 15 patients in HMA group and 9 patients in convention chemotherapy group achieved a complete remission before transplant. Thirty, 47 and 6 patients received transplants from matched related donors (MRD), matched unrelated donors (MUD), and mismatched related or unrelated donors (MMD), respectively. The sources of hematopoietic stem cells were peripheral blood for 48 patients (57.8%) and bone marrow for 35 patients (42.2%). Conditioning regimens varied; most patients received either fludarabine in combination with busulfan or fludarabine combined with melphalan. Sixty-four patients received myeloablative and 19 patients received reduced intensity conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. Patient and transplant characteristics did not significantly differ between the patients treated with HMA and the patients treated with conventional chemotherapy or given supportive care alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), Treatment related mortality (TRM), relapse incidence through last follow-up and incidences of acute GVHD and chronic GVHD. All of these outcomes were measured from the time of allo-SCT. Results Median follow up duration for 29 survivors was 48 months. Seventy-five patients engrafted (90.4%) with median time to neutrophil and platelet engraftment of 13 and 15 days respectively. Patients treated with a HMA had a significantly lower cumulative incidence (CI) of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplantdid not significantly differ between the groups (27% and 30%, respectively; p=0.84). Acute GVHD all grades and grade 2-4 were seen in 28.2% versus 35.8% (p=0.05) and 12.8% versus 11.3% (p=0.72) in patients who received a HMA compared to those who treated with other agents respectively. CI of chronic GVHD was 35% in patients treated with a HMA versus 19.2% in those treated with other agents (p=0.36) while CI of chronic extensive GVHD was seen in only 26.7% versus 19.2% respectively (p=0.64). The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a HMA (43%) than in those who received other treatments (27%; p=0.04) (Figure 1). However, therapy with HMA before transplant did not significantly influence the 3-year OS rate (45% in those treated with HMA and 39% in those treated with other agents; p=0.22). The independent prognostic factors for PFS were a blast count of < 5% before transplant (HR 0.36, 95%CI 0.14-0.78), treatment with a HMA (HR 0.44, 95% CI 0.23-0.86), a transplant from an MRD (HR 0.41, 95% CI 0.22-0.94), development of grade 2-4 acute GVHD (HR 2.7, 95% CI 1.27-5.77), and development of chronic GVHD (HR 0.15, 95% CI 0.05-0.45). Conclusion We conclude that treatment with hypomethylating agents before allo-SCT may improve survival in patients with CMML. Figure 1. Progression free survival Figure 1. Progression free survival Disclosures Alousi: Therakos, Inc: Research Funding. Andersson:Otsuka Research and Development, Inc.: Consultancy.

scholarly journals Clinical Outcome of Children With Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia Treated Between 1995 and 2005

2010 ◽  
Vol 28 (31) ◽  
pp. 4755-4761 ◽  
Author(s):  
Maurizio Aricò ◽  
Martin Schrappe ◽  
Stephen P. Hunger ◽  
William L. Carroll ◽  
Valentino Conter ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Clinical Outcome ◽  
Tyrosine Kinase ◽  
Leukocyte Count ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
The Impact

Purpose In a previous analysis of 326 children with Philadelphia chromosome (Ph) –positive acute lymphoblastic leukemia (ALL) treated between 1986 and 1996, hematopoietic stem-cell transplantation from HLA-matched related donors, but not from unrelated donors, offered a superior outcome than chemotherapy alone. To evaluate the impact of recent improvements in chemotherapy and transplantation, we performed a similar analysis on patients treated in the following decade. Patients and Methods We analyzed 610 patients with Ph-positive ALL treated between 1995 and 2005 without tyrosine kinase inhibitor therapy. The median follow-up duration was 6.3 years. Results Complete remission was achieved in 89% of patients. The 7-year event-free survival and overall survival rates were superior in the present cohort compared with the previous cohort (32.0% ± 2.0% v 25.0% ± 3.0, respectively, P = .007; and 44.9% ± 2.2% v 36.0% ± 3.0%, respectively, P = .017). Compared with chemotherapy alone, transplantation with matched related donors or unrelated donors in first remission (325 patients) showed an advantage with increasing follow-up, suggesting greater protection against late relapses (hazard ratio at 5 years, 0.37; P < .001). In the multivariate Cox regression analysis accounting for treatment (transplantation v no transplantation), age, leukocyte count, and early response had independent impact on treatment outcome. Conclusion Clinical outcome of children and adolescents with Ph-positive ALL has improved with advances in transplantation and chemotherapy. Transplantations with matched related donors and unrelated donors were equivalent and offered better disease control compared with chemotherapy alone. Age, leukocyte count, and early treatment response were independent prognostic indicators. The results of this study will serve as a historical reference to evaluate the therapeutic impact of tyrosine kinase inhibitors on the outcome of Ph-positive ALL.

Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen

Blood ◽  
2002 ◽  
Vol 99 (3) ◽  
pp. 1071-1078 ◽  
Author(s):  
Ronjon Chakraverty ◽  
Karl Peggs ◽  
Rajesh Chopra ◽  
Donald W. Milligan ◽  
Panagiotis D. Kottaridis ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Hla Class I ◽  
Unrelated Donor ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Primary Graft Failure ◽  
Related Mortality

Abstract A nonmyeloablative conditioning regimen was investigated in 47 patients with hematological malignancy receiving allogeneic progenitor cells from matched, unrelated donors. The median patient age was 44 years. The majority of patients had high-risk features, including having failed a prior transplantation (29 individuals). Twenty of the transplants were mismatched for HLA class I and/or class II alleles. Recipient conditioning consisted of 20 mg CAMPATH-1H on days −8 to −4, 30 mg/m2fludarabine on days −7 to −3, and 140 mg/m2 melphalan on day −2. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine A alone. Primary graft failure occurred in only 2 of 44 evaluable patients (4.5%). Chimerism studies in 34 patients indicated that the majority (85.3%) attained initial full donor chimerism. Only 3 patients developed grade III to IV acute GVHD, and no patients have yet developed chronic extensive GVHD. The estimated probability of nonrelapse mortality at day 100 was 14.9% (95% confidence interval [CI], 4.7%-25.1%). With a median follow-up of 344 days (range, 79-830), overall and progression-free survivals at 1 year were 75.5% (95% CI, 62.8%-88.2%) and 61.5% (95% CI, 46.1%-76.8%), respectively. In summary, a nonmyeloablative regimen incorporating in vivo CAMPATH-1H is effective in promoting durable engraftment in most patients and in reducing the risk of severe GVHD following matched unrelated donor transplantation.

"Prophylactic" Platelet (PLT) Transfusions in the Setting of Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT): Similar Clinical Efficacy of Single Donor (SDP) and Random Donor Pooled (RDP) Platelet Products.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 597-597
Author(s):  
Poliana A. Patah ◽  
Emel Gurkan ◽  
Rima Saliba ◽  
Marcos de Lima ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Median Time ◽  
Clinical Efficacy ◽  
Hemorrhagic Cystitis ◽  
Median Number ◽  
Hematopoietic Stem ◽  
Single Donor ◽  
Gvhd Prophylaxis ◽  
Conditioning Regimens ◽  
Related Donor ◽  
The Difference

Abstract Superiority of SDP over RDP for PLT transfusions is largely assumed, but unproven. We hypothesized that SDP and RDP used for prophylactic transfusions are clinically equivalent. Methods: In order to minimize the biases imposed by a heterogeneous population, we studied 33 patients (median age 47 years, range, 22–66), which underwent alloHSCT for AML or high-risk MDS with ABO-identical donors. All received intravenous busulfan (BU)-based myeloablative conditioning regimens: 30 patients received BU 130mg/m2 and fludarabine 40mg/m2 for 4 days, and 4 patients were given BU 0.8mg/kg every 6 hours for 4 days with cyclophosphamide 60mg/kg for 2 days. GvHD prophylaxis consisted of tacrolimus and mini-methotrexate. Recipients of unrelated (UD) or one antigen-mismatch related donor transplants received antithymocyte globulin (ATG). Source of stem cells was peripheral blood (n=23) and bone marrow (n=10). Donors were related (n=28) and UD (n=5). Only 3 patients were identified as alloimunized for RBC antigens before tranplant. Transfusions administered for active bleeding were excluded from this analysis. Prophylactic PLT transfusions were administered for PLT counts below 15 x 10e9/l. The corrected increment (CCI) was calculated according to standard formula, using PLT counts performed in samples collected following transfusions. As all patients received both types of products, each transfusion administered during the first 100 days after alloHSCT was evaluated individually. The RDP and SDP were labeled as ’ineffective’, according to the CCI: cut-offs of 5.5 for the samples collected in the first hour post transfusion, 5.0 for the samples between 1 and 18 hours and 4.5 for the samples collected 18 hours or later. Results: Median time to PLT engraftment was 13 days (range, 8–51, n=30). Patients received 105 RDP and 41 SDP transfusions. All RDP transfusions were ABO compatible, while 4 out of the 41 SDP (9.75%) were ABO-incompatible (p = 0.006). Median PLT and Hb level before transfusion were similar for both SDP and RDP. Frequency of amphotericin and vancomycin use, and presence of fever on transfusion day was similar on both groups. Median post-transfusion platelet count was 51K/μL (range, 5K-118K) after SDP and 36K/μL (range, 3K–115K) after RDP (p = 0.0004). Median CCI was 14.178 for SDP transfusions versus 7.793 after RDP (p = 0.0001). The difference in post-transfusion PLT counts and CCI favoring the SDP group did not translate into superior clinical efficacy. Median time to another PLT transfusion was 3 days (range, 0–10) after SDP and 2 days (range, 0–10) after RDP (p = 0.3). The median number of new transfusions needed in the following week was similar for both groups (2 transfusions, range 0–7). In the week following any given transfusion, 24% versus 16% of the patients receiving SDP versus RDP did not need other transfusion (p = 0.2); 17% of SDP and 30% of RDP transfusions were labeled ’ineffective’ according to CCI (p = 0.1). There were two episodes (6%) of hemorrhage during the study period (none lethal): gastro-intestinal and hemorrhagic cystitis. Conclusion: SDP transfusions produced a greater increment in PLT counts after transfusion, but SDP and RDP were equally effective in preventing hemorrhage.

Comparison Of Intravenous With Oral Busulfan In Allogeneic Hematopoietic Stem Cell Transplantation With Myeloablative Conditioning Regimens For Pediatric Acute Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3397-3397
Author(s):  
Motohiro Kato ◽  
Yoshiyuki Takahashi ◽  
Daisuke Tomizawa ◽  
Yasuhiro Okamoto ◽  
Jiro Inagaki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Outcome ◽  
Acute Leukemia ◽  
Pediatric Patients ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Significant Survival ◽  
The Difference

Abstract Recently, intravenous busulfan (iv-BU) has replaced oral-BU, which can suppress variety of bioavailability. Also, iv-BU showed less hepatic toxicity by avoiding the hepatic first-pass effect of oral-BU. Previous reports showed that the use of iv-BU reduced early complications and decreased early non-relapse mortality (NRM). Some reports demonstrated that iv-BU may provide better overall survival (OS) in adult with malignant diseases. Although several reports have been published on pediatric patients using iv-BU, the number of patients included was small, and the reports mainly focused on acute toxicity or early clinical outcome because of a short follow-up period. Thus, the role of iv-BU in HSCT for pediatric patients with acute leukemia is yet to be determined. In this study, to compare clinical outcome of HSCT with iv-BU and oral-BU, we retrospectively analyzed HSCT based on data reported to the Japan Society for Hematopoietic Cell Transplantation (JSHCT) registry. The patients were selected according to the following criteria: (1) patients diagnosed with either acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML), (2) aged 15 years or younger when receiving HSCT, (3) BU-based myeloablative (more than 8 mg/kg) preconditioning regimens, and (4) HSCT performed between 2000 and 2010. Therefore, we analyzed 460 children with iv-BU (n = 198) or oral busulfan (BU) (n = 262) receiving hematopoietic stem cell conditioning transplantation (HSCT) with BU-based myeloablative conditioning for acute leukemia. The median age at HSCT was 4 years (range, 0–15 years). The median follow-up period was 1,828 days (range, 85–4,619 days) after HSCT in all the surviving patients, and 1,185 days (range, 100–3,759 days) after HSCT in the iv-BU patients. Although OS with iv-BU and oral-BU at day 100 after HSCT was 72.5 ± 3.2% and 66.9 ± 2.9%, respectively, OS at 3 years after HSCT was similar (iv-BU, 53.4 ± 3.7%; oral-BU, 55.1 ± 3.1% ), and the log-rank test for OS did not show statistically significant difference (p = 0.77) (Figure 1a). The result was concordant even when an analysis was limited to patients with ALL or AML. OS at 3 years for patients with ALL using iv-BU (n = 90) and oral-BU (n = 151) was 56.4 ± 5.5% and 54.6 ± 4.1, respectively (p = 0.51) (Figure 1b). OS at 3 years for patients with AML using iv-BU (n = 108) and oral-BU (n = 111) was 51.0 ± 5.0% and 55.8 ± 4.8%, respectively (p = 0.83) (Figure 1c). The similarity of OS was reproduced even with the limited cohort of 247 patients who received HSCT after 1st CR or 2nd CR without prior HSCT. OS at 3 years was 78.3 ± 4.2% for iv-BU patients (n = 98) and 78.7 ± 3.4% for oral-BU patients (n = 149) and the difference was not statistically significant (p = 0.66). Multivariate analysis also showed no significant survival advantage with iv-BU. Cumulative incidence of relapse at 3 years with iv-BU was similar with that of oral-BU (39.0 ± 3.6% and 36.4 ± 3.1%, respectively) (p = 0.67). Cumulative incidence of NRM at 3 years was 16.6 ± 2.7% with iv-BU and 18.3 ± 2.5% with oral-BU (p = 0.51). The iv-BU group showed a tendency toward higher engraftment probability at day 60 (96.0 ± 1.5%) compared with the oral-BU group (89.3 ± 2.0%), but the difference was not statistically significant (p = 0.22) This study was a retrospective study using registry data, and there are some limitations of our data. For example, as selection of iv-BU or oral-BU was strongly associated with the transplantation period, which may have introduced bias. Further prospective studies are required to establish an optimal allogeneic HSCT treatment strategy for pediatric patients with acute leukemia. In conclusion, our study provides valuable information on the role of iv-BU in myeloablative HSCT for pediatric acute leukemia. In children, iv-BU could not show significant survival improvement in outcome of acute leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals THE DISCRIMINATE ABILITY OF THE PEDIATRIC ADOLESCENT SHOULDER SURVEY (PASS)

2019 ◽  
Vol 7 (3_suppl) ◽  
pp. 2325967119S0018
Author(s):  
Tracey Bastrom ◽  
Andrew Pennock ◽  
Eric W. Edmonds
Keyword(s):  
Surgical Treatment ◽  
Shoulder Instability ◽  
Shoulder Function ◽  
Compensatory Mechanisms ◽  
Minimal Impact ◽  
Shoulder Dysfunction ◽  
Operative Outcomes ◽  
The Difference

Purpose: The purpose of this study was to examine whether improvements in the Pediatric and Adolescent Shoulder Survey (PASS) are seen at 3 months following surgical treatment for shoulder instability and whether the PASS can discriminate between patients with differing outcomes based on clinical exam and the single assessment numeric evaluation (SANE). Performance of the PASS was contrasted with an adult validated tool, the quickDASH. Methods: Patients who underwent surgical treatment for shoulder instability with completed PASS forms available at pre-operative and 3 months post-operative (range 2.5-4.5mos) were included in this review. The PASS consists of 13 questions that assess (in child friendly language) symptoms, limitations, need for compensatory mechanisms, and emotional distress related to shoulder dysfunction. Responses are on a 0-5 or 0-10 scale with a score calculation based on percentage of total possible points (100% indicates no/minimal impact on quality of life from shoulder dysfunction). Patients were grouped based on range of motion or strength (within 10 degrees to contralateral extremity or no discrepancy in strength score was considered no deficit) and SANE score (=80% vs <80%) at the 3-month visit. Alpha was set at p<0.05 to declare significance. Results: 50 patients with a mean age of 16 years (range 13.5-18 yrs) were identified in this review with a mean post-operative follow-up of 3.2 ± 0.5 months. Scores on the PASS improved significantly from pre-operative (57 ± 16%) to post-operative (74 ± 16%, p<0.001). The quickDASH similarly showed improvement (27 ± 16 pre vs 18 ± 16 post, p=0.003) although the magnitude of the effect for the PASS was larger (f=0.84 for PASS vs f=0.48 for quickDASH). Ceiling effect (>15% reporting the highest score) was observed at 3 months with the quickDASH (16% with top score), but not with the PASS (4%, p=0.03). While both tools were able to discriminate between patients with SANE score =80% vs <80%, the difference in quickDASH score between patients with/without diminished motion did not reach significance (p=0.07, Table). Conclusion: The PASS shows anticipated improvements in shoulder function following surgical intervention for instability without ceiling effects. The PASS is able to discriminate between patients with differing post-operative outcomes at 3 months following surgery. [Table: see text]

scholarly journals Nonmyeloablative Allogeneic Stem-Cell Transplantation for Hematologic Malignancies: A Systematic Review

2003 ◽  
Vol 10 (1) ◽  
pp. 17-41 ◽  
Author(s):  
Benjamin Djulbegovic ◽  
Jerome Seidenfeld ◽  
Claudia Bonnell ◽  
Ambuj Kumar
Keyword(s):  
Stem Cell ◽  
Case Series ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Cell Transplants ◽  
Unrelated Donors ◽  
Conditioning Regimens ◽  
Prospective Case Series ◽  
Patient Selection Criteria

Background Increasingly, clinicians advocate the use of nonmyeloablative allogeneic stem-cell transplants (NM-allo-SCTs, “mini-transplants”) to manage hematologic malignancies. They hypothesize that NM-allo-SCT is equally efficacious to standard allo-SCT but produces less regimen-related toxicity. Methods To analyze available evidence on the benefits and harms of “mini-transplants,” we identified 23 manuscripts, 1 abstract, and 1 letter that reported the outcome of mini-transplants in hematologic malignancies. Results Data were compiled on 603 treated patients, with 118 transplants using stem cells from matched unrelated donors. All studies were small prospective case series, and most lacked concurrent or historical controls. Outcomes of interest were not uniformly reported. The studies were heterogeneous and used different patient selection criteria, conditioning regimens, and timing of transplant with respect to disease status. The transplant-related mortality rate was 32%, the relapse rate was 15%, and toxicities included acute and chronic graft-vs-host disease and veno-occlusive disease. The aggregate rate of complete remission was 45%. Survival at 1 year or longer ranged from 30% to 60% at 1 to 5 years of follow-up. All studies reported successful chimerism. Conclusions Disease-specific studies with longer follow-up are needed to evaluate this potentially promising therapy.

Impact of HLA Class I Typing-Resolution and Mismatches on Survival and Graft-Versus-Host Disease in Patients after Hematopoietic Stem Cell Transplantations from Unrelated Donors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2060-2060
Author(s):  
Miroslaw Markiewicz ◽  
Jerzy Wojnar ◽  
Malgorzata Krawczyk-Kulis ◽  
Iwona Wylezol ◽  
Sebastian Giebel ◽  
...  
Keyword(s):  
High Resolution ◽  
Relapse Rate ◽  
Graft Failure ◽  
Statistical Significance ◽  
Chronic Gvhd ◽  
Hla Class I ◽  
Class I ◽  
Hematopoietic Stem ◽  
Unrelated Donors ◽  
Grade 3

Abstract We analyzed 150 consecutive patients (pts) transplanted from unrelated donors (URD) at single institution- Silesian Medical Academy in Katowice- with use of the same standard operating procedure from February 1997 until December 2004 for CML (74 pts), AML (28), ALL (27), SAA (9), MDS (7), MM (1), NHL (1), PNH (1), OMF (1), bi-phenotypic AL (1). 92 pts were transplanted from matched donors, including 59 with complete 10 alleles (HLA-A,B,C,DRB1,DQB1) high resolution (HR) DNA-typing; and 33 with first class match established on base of low-resolution (LR) (13), serological (7) or un-complete typing without HLA-C (13) and second class HR typing. 58 pts were transplanted from mismatched donors (first class typing was HR in 43, LR in 14 and serological in 1 pt): 22 with single allelic mismatch (2 HLA-A, 7-B, 6-C, 7-DQB1), 33 with single HLA-C antigen mismatch and 3 with double mismatches (2 B+C, 1 C+C). Survival advantage at 4 years, although without statistical significance (p=0.16), was observed in the group of pts transplanted from 10/10 alleles matched donors (36+/− 11%) over those with mismatched donors (24+/− 11%). Oppositely, pts transplanted from matched donors who were not completely typed in HR did not achieve better survival (23+/− 17%). Poorest survival (13+/− 12%, p=0.007) was observed in patients transplanted from mismatched homozygous donors (n=10). The risk of acute GVHD grade 3–4 was increased (p=0.007) in pts with mismatched donors (31+/− 6%) when compared to matched completely typed in HR (10+/− 4%). Also the rate of graft failure tended to be lower in pts with matched than mismatched donors (5.1% versus 10.2%, p=0.25). In contrast, relapse rate was lower in mismatched (23+/− 10%) than in HR matched pts (34+/− 12%, p=0.55) what may reflect better GVL effect in mismatched transplant recipients. Unexpectedly, the rate of chronic GVHD was similar in pts with 10/10 alleles matched and mismatched donors (40+/− 10% versus 42+/− 9%, p=0.75). These results indicate that complete high resolution HLA class I typing is necessary for adequate selection of unrelated donors. Class I HLA-B and -C mismatches influence both survival and serious a-GVHD incidence. 10/10 alleles matched mismatched p survival at 4 years 36+/− 11% 24+/− 11% 0.16 aGVHD grade 3–4 10+/− 4% 31+/− 6% 0.007 graft failure rate 5.1% 10.2% 0.25 relapse rate 34+/− 12% 23+/− 10% 0.55 cGVHD 40+/− 10% 42+/− 9% 0.75 10/10 alleles matched mismatched homozygous donors p survival at 4 years 36+/− 11% 13+/− 12% 0.007

Results of T Cell Depleted (TCD) Myeloablative Hematopoietic Stem Cell Transplants (HSCT) in Patients with Hematologic Malignancies ≥ 55 yrs of Age.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3660-3660
Author(s):  
Ann A. Jakubowski ◽  
Esperanza B. Papadopoulos ◽  
Hugo R. Castro-Malaspina ◽  
Katharine Hsu ◽  
Miguel-Angel Perales ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
High Risk Patient ◽  
Disease Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Conditioning Regimens ◽  
Good Risk

Abstract Allogeneic HSCT remains the only curative therapy for many patients(pts) with hematologic diseases. Studies have suggested that older pts experience greater toxicity from the intensive chemo-radiotherapy used in myeloablative conditioning regimens. As a consequence, many older pts are now offered non-myeloablative transplants (NMAT) for malignant conditions where a graft vs. tumor effect (GvT) is expected to provide the antitumor effect in place of the chemo-radiotherapy. Unfortunately, graft vs. host disease (GvHD) remains a common occurrence after conventional transplants, occurring more frequently in older pts and unrelated donor transplant recipients, resulting in significant morbidity and mortality. Furthermore, the efficacy of NMAT is limited by the disease status at time of transplant and by the susceptibility of the hematologic disease to a GvT effect. TCD of hematopoietic stem cell grafts offers an alternative to older pts, in particular those requiring unrelated donor transplants (URD), with the advantage of a reduced incidence of GvHD. From 1995–2005, 57 patients ≥55 yrs received myeloablative TCD transplants at our institution. The median age was 58.2 (range 55–69.2) yrs. Stem cell sources were TCD bone marrow, PBSC or both. Thirty-seven received transplants from related donors (RD), including two mismatched, and 20 received transplants from unrelated donors (URD), 9 of whom were mismatched. In addition to their advanced age, many of these pts were considered high risk based on the status of disease, HLA mismatch, and history of previous therapy. Twenty-three pts were considered “good risk” by disease status (CML-CP1, AML-CR1, CR2) and 34 pts were considered poor risk (&gt;CML-CP1, &gt;AML CR2, MDS, NHL, &gt;ALL CR1, ABL.) BM was TCD by soybean agglutination followed by sheep red blood cell rosetting (E), and PBSCs by CD34+ selection and E-rosetting. Conditioning regimens included total body irradiation (TBI) in addition to thiotepa and cyclophosphamide, or thiotepa and fludarabine. The non-TBI preparative regimen consisted of busulphan, melphalan and fludarabine. Anti-thymocyte globulin was used as rejection prophylaxis for all TCD transplants until 2001 when it was eliminated from the TBI containing regimen for matched RD transplants. A total of 25 pts (15 matched RD and 10 URD, 6 of whom were mismatched) are alive following TCD transplants with a median follow up of 24 mos. for RDs and 12 for URDs. Of the survivors, 2/10 URD and 14/15 RD recipients received TBI containing regimens based on the triage system at our center. Three pts with CML-CP1, one with CML-acc and one with AML-CR1 showed evidence of minimal residual disease, received donor leukocyte infusions and subsequently achieved longterm continued CR. The incidence of post-transplant GvHD was low despite the high number of mismatched URD transplants - 1 Grade IV (RD), 2 Grade 3 and 1 Grade 1 (URD). The 100 day mortality was 15%. Overall and current disease free survival for ‘good risk’ patients based on disease status is 58% for RD and 60% for URD. Although longer follow up is necessary to confirm these results, the promising DFS rates in association with a low incidence of GvHD in this older and relatively high risk patient population support further investigation of myeloablative TCD HSCT in these patients.

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