Red Blood Cell Deformability and Distribution Width in Patients with Hematologic Neoplasms.

BACKGROUND: Despite increasing evidence that red blood cell (RBC) deformability is impaired in pathologic conditions, little research has been done on RBC deformability in hematologic diseases. The authors measured RBC deformability in patients with various hematologic diseases, including hematologic malignancies. METHODS: A total of 568 patients who underwent bone marrow (BM) examination for initial diagnosis were enrolled. We collected the subjects' age, gender, diagnosis of BM examination, and complete blood count results. The RBC deformability, which was quantified by an elongation index, was measured by a microfluidic ektacytometer. RESULTS: RBC deformability was lower in primary myelofibrosis, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) from least to greatest. When the correlation between red blood cell distribution width (RDW) and RBC deformability was analyzed for 370 subjects in hematologic neoplasms, the correlation coefficient of RDW was -0.2974 (p < 0.01). When comparing MDS and aplastic anemia (AA), the deformability of MDS was significantly lower than that of AA. CONCLUSIONS: RBC deformability was decreased in leukemic diseases such as AML, MDS, CML, and ALL compared to control, and RDW showed a negative correlation with deformability. RBC deformability may be used as a complementary differential diagnostic test for MDS and AA.

COVID-19 transmission and blood transfusion: A case report.

The recent outbreak of the novel coronavirus disease 2019 (COVID-19) has been labelled as a pandemic by the World Health Organization. Although person-to-person transmission of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been confirmed, it is not known whether COVID-19 may be transmitted by blood transfusion. Notwithstanding the urgent requirement of blood, it is critical to know whether the SARS-CoV-2 virus can be transmitted by blood transfusion because many individuals may be asymptomatic carriers and may donate blood. Several cases in which specific viral RNA could be detected in the serum from patients with COVID-19 have already been reported; these findings suggest that blood donation may be an unexplored route of transmission. However, the American Association of Blood Banks and Centers for Disease Control and Prevention have not recommended any specific SARS-CoV-2-related actions to be taken at blood collection centres at this time. In this report, we describe a case of a 21-year-old man with very severe aplastic anaemia who received apheresis platelet transfusion from an individual who was subsequently diagnosed with COVID-19. Our patient tested negative for COVID-19 and is awaiting allogeneic stem cell transplantation.

Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type NPM1 without FLT3-ITD.

BACKGROUND: The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1 wt/FLT3-ITDneg/low) has not yet been elucidated. METHODS: In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. RESULTS: According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1 wt/FLT3-ITDneg/low, complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1 wt/FLT3-ITDneg/low group (P=0.233). Among the intermediate-risk NPM1 wt/FLT3-ITDneg/low patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. CONCLUSION: Among the AML patients, intermediate-risk NPM1 wt/FLT3-ITDneg/low patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1 wt/FLT3-ITDneg/low patients. Well controlled studies are needed to confirm the current results.

Impact of Consolidation Cycles Before Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission.

BACKGROUND: The optimal number of high-dose cytarabine (HDAC) consolidation cycles before allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia is not fully standardized. PATIENTS AND METHODS: This study evaluated the impact of HDAC consolidation cycles before allogeneic HCT in 194 patients with acute myeloid leukemia in first complete remission between 1998 and 2014. The patients were reclassified into 3 groups-no consolidation (C0, n = 20), 1 consolidation (C1, n = 115), and ≥ 2 consolidations (C2, n = 59)-by pre-HCT consolidation cycle. RESULTS: The 3-year relapse-free survival rates was 45.9%, 66.9%, and 73.3% for the C0, C1, and C2 groups, respectively (P = .064), while the 3-year overall survival rates were 35.0%, 55.2%, and 67.5%, respectively (P = .106). The cumulative incidence of acute graft-versus-host disease (GVHD) was higher in the C2 group (38.7%) than in the C0 (22.2%) or C1 (17.7%) group (P = .018). However, the incidence of chronic GVHD showed no difference between the groups. Multivariate analysis for overall survival revealed the following independent factors: adverse cytogenetic risk (hazard ratio [HR] = 1.84, P = .046), C2 versus C0 (HR = 0.41, P = .037), pre-HCT status beyond CR1 versus CR1 (HR = 5.78, P < .001), and presence of chronic GVHD (HR = 0.45, P = .004). CONCLUSION: One or two cycles of HDAC consolidation therapy led to better subsequent HCT outcomes compared to the no-consolidation therapy group.

Adipose-Derived Regenerative Cell Injection Therapy for Postprostatectomy Incontinence: A Phase I Clinical Study.

PURPOSE: We report our initial experience with transurethral injection of autologous adipose-derived regenerative cells (ADRCs) for the treatment of urinary incontinence after radical prostatectomy. MATERIALS AND METHODS: After providing written informed consent, six men with persistent urinary incontinence after radical prostatectomy were enrolled in the study. Under general anesthesia, about 50 mL of adipose tissue was obtained from the patients by liposuction. ADRCs were obtained by separation with centrifugation using the Celution cell-processing device. A mixture of ADRCs and adipose tissue were transurethrally injected into the submucosal space of the membranous urethra. Functional and anatomical improvement was assessed using a 24-h pad test, validated patient questionnaire, urethral pressure profile, and magnetic resonance imaging (MRI) during 12-week follow-up. RESULTS: Urine leakage volume was improved with time in all patients in the 24-h pad test, with the exemption of temporal deterioration at the first 2 weeks post-injection in 2 patients. Subjective symptoms and quality of life assessed on the basis of questionnaire results showed similar improvement. The mean maximum urethral closing pressure increased from 44.0 to 63.5 cm H2O at 12 weeks after injection. MRI showed an increase in functional urethral length (from 6.1 to 8.3 mm) between the lower rim of the pubic bone and the bladder neck. Adverse events, such as pelvic pain, inflammation, or de novo urgency, were not observed in any case during follow-up. CONCLUSION: This study demonstrated that transurethral injection of autologous ADRCs can be a safe and effective treatment modality for postprostatectomy incontinence.

POEMS Syndrome with IgG-λ/IgA-κ Biclonal Gammopathy and Abnormal Serum Free Light Chain Ratio: a Case Report.

BACKGROUND: POEMS syndrome is a rare paraneoplastic disorder with atypical plasma cell proliferation. Cases of POEMS syndrome presented with either biclonal gammopathy or an abnormal serum free light chain ratio are considered uncommon. The present authors encountered a case of POEMS syndrome with IgG-λ/IgA-κ biclonal gammopathy with dominant κ free light chain and abnormal serum free light chain ratio. CASE: A 56-year-old man with a history of Castleman disease was suspected with POEMS syndrome and admitted for further evaluation for B-cell proliferative disease to rule out multiple myeloma. He also had a sustained tingling sensation on both feet and gait disturbance, which were compatible with diffuse peripheral sensorimotor polyneuropathy with demyelinating features. His laboratory findings revealed hyperlipidemia and hypothyroidism, and he had hypertrichosis. The results of the serum and urine protein electrophoresis seemed normal, except a very weak band at the end of the serum gamma region. Serum immunofixation electrophoresis confirmed IgG-λ and IgA-κ biclonal gammopathy, with an increased serum IgA concentration and normal levels of IgG, IgM, and IgD. Both serum free light chain κ and λ values were increased, and the κ/λ ratio was higher than normal. CONCLUSIONS: The finding of IgG-λ/IgA-κ biclonal gammopathy and abnormal serum free light chain ratio with dominant κ clonality in our case was definitely rare. However, a primary pathogenic role of the different paraproteinemia in POEMS syndrome remains unclear. Further studies to identify better management modalities for POEMS syndrome is needed.

Benefits of fresh-frozen plasma as a replacement fluid to neutralize ABO antibodies.

BACKGROUND: ABO-incompatible organ transplantation requires pre-transplant conditioning to reduce ABO antibody levels in the recipients. With respect to replacement fluids used in plasma exchange, we intended to verify whether fresh-frozen plasma (FFP) containing soluble ABO substance (SAS) is more effective than albumin solution in reducing ABO IgG antibody levels. METHODS: Apheresis data were retrospectively studied for in vivo effects, and in vitro plasma mixing studies were prospectively performed. The amount of ABO IgG antibodies bound to red cells was measured as the mean fluorescence intensity (MFI) using flow cytometry. Neutralization of ABO antibodies in the recipientst plasma by an ABO-incompatible donornc plasma was measured using the inhibition assay principle. The MFI value of the unneutralized control tube was divided by that of the neutralized test tube (neutralizing-capacity index, NCI). RESULTS: The plasma exchange procedures replaced with group AB FFP showed a significantly greater decreased titer than those replaced with albumin (P = 0.010). The in vitro plasma mixing study simulating plasma exchange also produced consistent results. When the pooled group O plasma was neutralized for anti-A by individual group AB plasmas (AB-to-O, N = 30), the NCI was 12.8 ± 5.4 (6.5-29.5). When this group O plasma was neutralized by pooled group AB or A plasma, the repeatedly measured NCI (N = 5) of A-to-O (11.4 ± 1.4) was not significantly different from that of AB-to-O (9.7 ± 1.3, P = 0.074). CONCLUSIONS: ABO antibody levels are reduced more effectively by group AB FFP than by albumin. Either group AB or donor type (group A or B) FFP can be infused to group O recipients. FFP units with higher SAS levels can be selected from multiple available candidate units using our protocol for measuring the neutralizing-capacity.

Outcomes of allogeneic hematopoietic cell transplantation in acute myeloid leukemia patients with monosomal karyotypes.

This study investigated the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) patients with monosomal karyotypes (MK). A total of 114 AML patients who received allo-HCT were retrospectively analyzed. At the time of diagnosis, 13 patients were categorized with a favorable cytogenetic risk, 78 with an intermediate risk, and 23 with an adverse risk. MK was found in 12 patients among 23 with adverse cytogenetic risk. Pretransplant disease status was active disease in 5 cases (45.5%) in the adverse-risk without MK group, and 8 cases (66.7%) in the corresponding group with MK, 15 (19.2%) in the intermediate group and 4 (30.8%) in the favorable group. In multivariate analysis, active disease before transplant (hazard ratio, HR 3.913, p < 0.001), acute graft-versus-host disease (GVHD) ≥grade 2 (HR 1.908, p = 0.048) and chronic GVHD (HR 0.364, p = 0.001) affected overall survival (OS). The initial cytogenetic risk groups were not a significant risk factor for OS in allogeneic settings. The 2-year OS rate was 44.0 ± 15.9% without MK and 20.7 ± 17.9% with MK (p = 0.246). However, the OS rate was better for patients with chronic GVHD (p = 0.025). In conclusion, a survival benefit was observed for MK-positive patients with chronic GVHD in an allogeneic setting. However, the prognosis still remained poor for patients with MK.

Analysis of the Ten-Eleven Translocation 2 (TET2) gene mutation in myeloproliferative neoplasms.

Loss-of-function mutations in the putative tumor suppressor gene, Ten-Eleven Ttranslocation 2(TET2), have been identified recently in myeloproliferative neoplasms (MPNs). The present study analyzed the TET2 gene in 99 MPNs patients. The overall TET2 mutational frequency was 12.1% (22.2% in polycythemia vera (PV), 9.7% in essential thrombocythemia (ET), 18.2% in primary myelofibrosis (PMF,) and 0% in unclassified MPNs), and 11 mutations (p.Lys95Asnfs*18, p.Gln967Asnfs*40, p.Lys1022Glufs*4, p.Asp1314Metfs*49, p.Gln1534Alafs*43, p.Tyr1618Leufs*4, p.Leu1609Glufs*45, p.Gly1735*, Q599R, c.3409+1G>T, c.4044+2insT) were identified. All the patients with TET2 mutation were accompanied by the JAK2 V617F mutation. The existence of the TET2 mutation was not related to the patient's age, hematologic indices, JAK2 V617F allele burden, frequencies of organomegaly, marrow fibrosis, or thrombotic/hemorrhagic complications in entire MPN patients. However, tendencies toward higher JAK2 V617F allele burdens (88.0±4.3% vs. 19.1±28.7%, P=0.034) and higher Hct (47.4±5.4% vs. 25.5±6.2%, P=0.037) were detected in PMF patients harboring TET2 mutations. Moreover, a significantly higher frequency of organomegaly was identified in ET patients harboring the TET2 mutation (50% vs. 19.6%, P=0.018). The TET2 mutation most likely contributes to clinical phenotypes and shows a high accompanying rate with JAK2 V617F; larger scale studies involving more MPN patients are needed.

Feasibility of non-TBI conditioning with busulfan and fludarabine for allogeneic stem cell transplantation in lymphoid malignancy.

BACKGROUND/AIMS: This retrospective study evaluated the transplantation outcomes of patients with adult lymphoid malignancies who received chemotherapy-based conditioning with busulfan and fludarabine (BuFlu) and busulfan and cyclophosphamide (BuCy2). METHODS: Thirty-eight patients (34 with acute lymphoblastic leukemia and 4 with lymphoblastic lymphoma) were included in the current study. The conditioning regimen was BuCy2 for 14 patients and BuFlu for the remaining 24 patients. Eight and 13 patients were high risk disease in the BuCy2 and BuFlu groups, respectively. RESULTS: The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 56.5% and 55.2% and that of extensive chronic GVHD 17.0% and 55.6% (p = 0.018) for the BuFlu and BuCy2 groups, respectively. The 3-year relapse rate was 27.8% and 31.4% and 3-year overall survival 34.3% and 46.8% for the BuFlu and BuCy2 groups, respectively. Treatment-related mortality (TRM) was significantly lower in the BuFlu group (16.9%) than in the BuCy2 group (57.1%, p = 0.010). In multivariate analyses, the BuFlu regimen was identified as an independent favorable risk factor for TRM (hazard ratio [HR], 0.036; p = 0.017) and extensive chronic GVHD (HR, 0.168; p = 0.034). CONCLUSIONS: Our BuFlu regimen would appear to be an acceptable conditioning option for lymphoid malignancies, including high-risk diseases. It was safely administered with a lower TRM rate than BuCy2 conditioning.

Pilot study on combination of azacitidine and low-dose cytarabine for patients with refractory anemia with excess blast.

This study analyzed the outcomes of the combination of azacitidine and low-dose cytarabine in patients newly diagnosed with refractory anemia with excess blast (RAEB). Patients were treated with azacitidine 75 mg/m(2) for 7 days subcutaneously and cytarabine 20 mg/m(2) intravenously for 7 days every 28 days. The assigned regimen was repeated for two cycles, then the patients treated with azacytidine alone until progression or allogeneic stem cell transplantation (allo-SCT). Eighteen patients with 5 RAEB-1 and 13 RAEB-2 were enrolled in the current study. After two cycles of the combination therapy, responses were achieved in nine patients (50.0%): four complete response (CR) (22.2%), one partial response (5.6%), two marrow-CR (11.1%), and two hematologic improvement (11.1%). Four patients (22.2%) progressed to acute leukemia during two cycles of the combination therapy. The 1-year overall survival (OS) was 87.5% for the early response group (responses at two cycles) and 0% for the late response group (responses at four cycles, p = 0.042). Plus, the median survival time was 476 days (range, 37-718 days) for the early response group and 221 days (range, 193-249 days) for the late response group. The 1-year OS was 100% for the patients who underwent allo-SCT and 73.4% for those without allo-SCT. In summary, the combination therapy showed promising response rate when compared to treatment with azacitidine alone. However, it was limited in terms of preventing leukemic transformation. Allo-SCT would seem to be the only available treatment that can alter disease progression.

Novel ELANE gene mutation in a Korean girl with severe congenital neutropenia.

Severe congenital neutropenia is a heterozygous group of bone marrow failure syndromes that cause lifelong infections. Mutation of the ELANE gene encoding human neutrophil elastase is the most common genetic alteration. A Korean female pediatric patient was admitted because of recurrent cervical lymphadenitis without abscess formation. She had a past history of omphalitis and isolated neutropenia at birth. The peripheral blood showed a markedly decreased absolute neutrophil count, and the bone marrow findings revealed maturation arrest of myeloid precursors at the promyelocyte to myelocyte stage. Her direct DNA sequencing analysis demonstrated an ELANE gene mutation (c.607G > C; p.Gly203Arg), but her parents were negative for it. She showed only transient response after subcutaneous 15 µg/kg/day of granulocyte colony stimulating factor administration for six consecutive days. During the follow-up observation period, she suffered from subsequent seven febrile illnesses including urinary tract infection, septicemia, and cellulitis.

Genome-wide high density single-nucleotide polymorphism array-based karyotyping improves detection of clonal aberrations including der(9) deletion, but does not predict treatment outcomes after imatinib therapy in chronic myeloid leukemia.

The current study investigated molecular cytogenetic characteristics of chronic myeloid leukemia (CML) using genome-wide, single nucleotide polymorphism arrays (SNP-A) capable of detecting cryptic submicroscopic genomic aberrations. Genome-Wide Human SNP 6.0 Array (Affymetrix, CA, USA) was performed in 118 patients having CML, chronic phase. Thirty-nine clonal aberrations (CAs) were identified (35 losses, two gains, two copy neutral loss of heterozygosity) that were not detected by metaphase cytogenetics in 25 patients (21%). The 9q34 deletions were found in 10% of cases, while 22q11.2 deletions were observed in 12% of cases. Seven patients (6%) harbored both 5'-ABL and 3'-BCR deletions adjacent to the t(9;22) breakpoint. Copy number gains were identified at 8p and 9p, and losses at 2q, 7q, 8q, 9q, 11q, 13q, 16p, and 22q. When we compared the treatment outcome of imatinib therapy between patients with and without CAs identified by SNP-A, treatment failure and progression to advanced disease were not significantly different (p > 0.05). In addition, according to the presence of deletions of 9q34 and/or 22q11.2 identified by SNP-A, the treatment outcome did not show any significant differences (p > 0.05). Our data suggests that SNP-A analysis is a useful tool for detection of clonal aberrations including deletions adjacent to the t(9;22) breakpoint in the CML cancer genome. However, clonal aberrations detected by SNP-A could not improve a prognostic stratification in CML patients with chronic phase.

Mobilization effects of G-CSF, GM-CSF, and darbepoetin-alpha for allogeneic peripheral blood stem cell transplantation.

The effects of GM-/G-CSF and darbepoetin-alpha on stem cell mobilization were investigated. From February 2005 to March 2007, 30 allogeneic sibling donors were randomly assigned to a G-CSF group (5 microg/kg/day for 5-7 days) or triple group (GM-CSF 10 microg/kg/day on 1st and 2nd day, G-CSF 5 microg/kg/day for 5-7 days, and darbepoetin-alpha 40 mg on 1st day). The MNCs and CD34(+) cells were not different between the two groups, although the doses (x10(8)/kg of recipient body weight) of CD3(+) cells (3.64 +/- 1.75 vs. 2.63 +/- 1.36, P = 0.089) and CD8(+) cells (1.07 +/- 0.53 vs. 0.60 +/- 0.30, P = 0.006) were lower in the triple group. The engraftments, frequency of RBC transfusions, and hemoglobin recovery were not different between the two groups. The cumulative incidence of overall and Grades II-IV aGVHD was 64.3% vs. 61.1% and 25.9% vs. 27.1% in the G-CSF and triple regimen group, respectively, whereas the cumulative incidence of cGVHD was 20.8 +/- 1.3% and 24.4 +/- 1.7%, respectively. In conclusion, the triple regimen did not seem to be superior to G-CSF alone in terms of the CD34+ cell dose, hemoglobin recovery, and GVHD. However, the CD8+ cell count was significantly lower in the triple regimen group. The role of a lower CD8+ cell count in the graft may need to be elucidated in the future.

Clinical significance of autoantibody expression in allogeneic stem-cell recipients.

BACKGROUND: The occurrence of autoantibodies has been reported in allogeneic stem-cell recipients, but the association of this occurrence with chronic graft-versus-host disease (cGVHD) or survival remains uncertain. METHODS: A total of 121 consecutive patients who underwent allogeneic stem-cell transplantation from November 2001 to March 2008 and survived at least 3 months after transplantation were included in this study. RESULTS: Forty-seven patients (38.8%) expressed at least one of various autoantibodies after transplantation. Antinuclear antibody was positive in 22 patients (18.2%), antidouble stranded DNA in seven (5.8%), antismooth muscle antibody in six (5%), rheumatoid factor in 17 (14.0%), and a positive Coombs test recorded for 12 patients (9.9%). cGVHD was more commonly diagnosed in the patients with autoantibody expression (61.7% vs. 43.2%, P=0.048). The patients expressing autoantibodies had a better 5-year overall survival than those without any autoantibody expression: 70.2% and 47.9% for the autoantibody-positive and autoantibody-negative patients, respectively (P=0.002). The cumulative incidence of relapse was 21.5% and 39.3% for the autoantibody-positive and autoantibody-negative patients, respectively (P=0.023). In particular, the patients expressing autoantibodies without cGVHD had a better overall survival (100%) than the patients in the other groups: 63.1% for the autoantibody- and cGVHD-positive patients, 59.6% for the autoantibody-negative and cGVHD-positive patients, and 36.6% for the autoantibody- and cGVHD-negative patients. The multivariate analysis identified autoantibody expression as a good prognostic factor regarding survival (hazard ratio=0.378, 95% confidence interval=0.185-0.775, P=0.008). CONCLUSION: The occurrence of autoantibodies after allogeneic stem-cell transplantation was found to be related to cGVHD, and patients expressing autoantibodies had a better survival.

Flow cytometric assessment of platelet aspirin resistance using light scattering.

BACKGROUND: A simple and reliable assay is needed for the prediction of the clinical efficacy of antiplatelet aspirin therapy. We have devised another method for the evaluation of platelet function and aspirin resistance (AR), via conventional flow cytometry (FCM). METHODS: To devise an optimized protocol for the assessment of platelet AR, various analytic variables of FCM were investigated. Using this devised protocol, AR was assessed in healthy subjects as an example. RESULTS: The protocol utilized herein is as follows: citrate-anticoagulated platelet-rich plasma was mixed 1:1 with HEPES-buffered saline in two tubes, one of which is treated with aspirin. During the acquisition of FCM, arachidonate is added to the tube. The response of the aspirin-treated platelets is then compared with those of nontreated ones on a time/forward scatter plot. In the 61 total subjects, none was identified as aspirin resistant by this assay. CONCLUSIONS: Using light scattering, platelet aggregation and aspirin's antiplatelet effects can be readily and cost-effectively detected. According to this assay, biochemical AR appears to be rare. This new protocol may prove useful in a clinical setting or as a research tool.

The association between multidrug resistance-1 gene polymorphisms and outcomes of allogeneic HLA-identical stem cell transplantation.

The impact of single nucleotide polymorphisms of two loci (C3435T and G2677T/A) of the multidrug resistance-1 gene (MDR1) was investigated in 82 patients undergoing allogeneic stem cell transplantation (SCT). The GG genotype on G2677T/A loci was associated with higher non-relapse mortality than was the non-GG genotype (67% vs. 32%, p=0.0073), but not the C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival was significantly correlated with the G2677T/A genotype (p=0.0048). Multivariate analysis also showed that the GG genotype at G2677T/A had an unfavorable prognosis in terms of overall survival (p=0.003) and non-relapse mortality (p=0.031). In conclusion, the G2677T/A genotype seems to be associated with transplantation outcomes, especially non-relapse mortality.

Non-CD34+ cells, especially CD8+ cytotoxic T cells and CD56+ natural killer cells, rather than CD34 cells, predict early engraftment and better transplantation outcomes in patients with hematologic malignancies after allogeneic peripheral stem cell transplantation.

The effect of the transplant dose of each cell subset on engraftment kinetics and transplantation outcomes was evaluated in HLA-identical allogeneic peripheral blood stem cell transplantation (PBSCT). Sixty-nine patients were included in this retrospective study. Engraftment kinetics, transplantation outcomes, and immune reconstitution up to 1 year after transplantation were analyzed according to the transplant dose of CD34+ and non-CD34+ cells, including natural killer (NK) cells and CD8+ cytotoxic T (Tc) cells. An accelerated neutrophil engraftment was strongly associated with a higher transplant dose of NK cells (12 versus 16 days, P < .001) and Tc cells (13 versus 16 days, P < .001) but not CD34+ cells (P = .442). Survival analyses revealed a favorable prognosis for patients who received a higher dose of non-CD34+ cell subsets, rather than CD34+ cells, in terms of overall survival (OS; P = .024 for NK cells and .050 for Tc cells) and nonrelapse mortality (NRM; P = .005 for NK cells, .060 for Tc cells). In addition, a higher transplant dose of NK and Tc cells was correlated with a faster lymphoid reconstitution. In multivariate analyses, rapid neutrophil engraftment was correlated with a higher transplant dose of NK cells (P = .001) and Tc cells (P = .004). Moreover, an increased OS was associated with the NK cell dose (P = .007) and chronic graft-versus-host disease (P = .009), whereas a decreased NRM was associated with the NK dose (P = .024). In conclusion, in a PBSCT setting, a higher transplant dose of NK and Tc cells accelerated neutrophil engraftment, improved the immune reconstitution, and decreased NRM, thereby increasing OS after allogeneic PBSCT.