Changing to a New Donor for Second Hematopoietic Stem Cell Transplantation in Fanconi Anemia Seems to Improve Survival.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2294-2294
Author(s):  
Korthof Elisabeth ◽  
Marlieke Ridder ◽  
Rosi Oneto ◽  
Andrea Bacigalupo ◽  
Johannes R Rischewski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Fanconi Anemia ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Study Population

Abstract Abstract 2294 Poster Board II-271 This retrospective analysis of the EBMT ProMISe database was designed to investigate the role of donor choice for second hematopoietic stem cell transplantation (HSCT) in Fanconi Anemia (FA). Our hypothesis was that using a different donor for the second HSCT would increase the probability of survival, the patient not being sensitized to donor antigens as a result of the first HSCT. We conducted a survey of the EBMT ProMISe database in order to identify FA patients transplanted more than once for bone marrow failure and retrospectively analyzed their data to determine overall survival and presence of acute GvHD. A donor for the second HSCT was defined as the “same” as for the first if both donors had identical: birth date, relation to patient (identical sibling or not), gender and family relation or donor number. A donor was “different” when this information indicated that a different person donated for second HSCT. One hundred and three patients were eligible for the study by the following criteria: diagnosis of Fanconi Anemia (confirmed by chromosome breakage test), presentation with aplastic anemia (AA) and having undergone two HSCTs between August, 1980 and December, 2007. FA patients with myelodysplasia or acute leukemia were excluded. After retracing data in the database, additional questionnaires were sent out to 44 EBMT centers that had performed second HSCTs for FA-AA, asking for supplementary data. In 80 cases (study population), enough information was collected to identify first and second donors. Forty four subjects (25 males and 19 females) received a second HSCT from the “same donor” (SD) and 36 patients (15 males and 21 females) from a “different donor” (DD). The mean age of the study population at second HSCT was 10.7 years (range, 1.8-34.5). Median interval between first and second HSCT was 63 days. At first HSCT patient gender, age at HSCT, use of cyclophosphamide and irradiation in the conditioning regimen and type of rejection were not differently distributed in the SD and DD group whereas significantly more HLA identical sibling donors were used in the SD (31%) vs. DD (11%) group (p=0.027). In 68.2% of the SD group bone marrow was used vs. in 52.7% of the DD group (p=0.002). Median cell dose in SD group was 9×106 CD34+/kg and in DD group 1.8×106 CD 34+/kg (p=0.002). At second HSCT age at HSCT, use of cyclophosphamide and irradiation in the conditioning regimen, dose of CD34+ cells and cell source were not differently distributed between SD and DD groups whereas significantly more HLA identical sibling donors were used in SD (31%) vs. DD (11%) group (p=0.027). Overall survival of all 80 patients at one year from second transplant is 36%. Probability of overall survival after 7 years is 35%. An interval between first and second HSCT of >80 days resulted in better survival (p=0.007). Overall survival at 7 years is 41% in DD and 26% in SD patients (Cox regression, HR 0.483, p=0.017). This difference remained significant after correction for the confounding effects of irradiation in first HSCT and relation donor/patient (identical sibling or not). Rejection rate after second HSCT was similar in SD and DD group (54.5%). Death occurred in 73% of SD vs. 56% of DD. Causes of death included infections (70% in SD vs. 48% in DD) and rejection (39% in SD and 38% in DD). Noteworthy more than one major cause of death was often found in the same patient. Only 2 secondary tumors were reported in the whole group. Acute GvHD gr II-IV was not significantly different in SD vs DD groups (multivariate logistic regression models, OR 1.642, p=0.47). Our data suggest that after having failed a first transplant, using the same or a different donor does not affect the occurrence of aGVHD, whereas change of donor would improve the survival of FA patients in need of a second HSCT for AA. Mechanisms underlying rejection of a first HSCT should be studied more in depth. International centers should collaborate in finding the most appropriate regimen for first and second transplants in FA. Disclosures: No relevant conflicts of interest to declare.

Successful Hematopoietic Stem Cell Transplantation Using an Immunosuppressive Conditioning Regimen in Ten Patients with Severe Congenital Neutropenia: A Single-Institute Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3688-3688
Author(s):  
Yoko Mizoguchi ◽  
Mizuka Miki ◽  
Aya Furue ◽  
Shiho Nishimura ◽  
Maiko Shimomura ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Hematopoietic Stem ◽  
Engraftment Failure

Abstract Severe congenital neutropenia (SCN) is a rare heterogeneous genetic disorder characterized by severe chronic neutropenia, with absolute neutrophil counts below 0.5×109/L, and by recurrent bacterial infections from early infancy. Granulocyte colony-stimulating factor (G-CSF) is widely used for the treatment of neutropenia in patients with SCN. However, the long-term G-CSF therapy has a relative risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The only curative treatment available for SCN patients is hematopoietic stem cell transplantation (HSCT). Recently, HSCTs with reduced intensity conditioning (RIC) regimens have been applied to the treatment of SCN patients without malignant transformation who have become G-CSF refractory. However, the optimal conditions of HSCT for SCN patients have not been established. In this study, we conducted bone marrow cell transplantations (BMT) in ten patients with SCN using an immunosuppressive conditioning regimen to minimize early and late transplant-related morbidity in Hiroshima University Hospital. Ten patients with a total of 11 HSCT procedures in our institution (performed from 2007 to 2015) were enrolled in this study. Four of the ten patients had experienced engraftment failure of the initial HSCT and three of them were referred to our hospital for re-transplantation. Heterozygous mutation inthe ELANE gene was identified in nine of ten patients. These nine patients received BMT less than 10 years of age. All ten patients had recurrently experienced moderate to severe bacterial or fungal infection before HSCT and received temporal or regular administration of G-CSF. Bone marrow cells (BM) were obtained from five HLA-matched related (MRD), three HLA-matched unrelated (MUD), and three HLA-mismatched unrelated (7/8) donors (MMUD), respectively. The conditioning regimen basically consisted of fludarabine (100 to 125 mg/m2), cyclophosphamide (100 to 150 mg/kg), melphalan (70 to 90 mg/m2), total body irradiation (3 to 3.6 Gy), and/or anti-thymocyte globulin (10 to 12 mg/kg). Short-term methotrexate and tacrolimus were administered for the prophylaxis of graft-versus-host disease (GVHD). Engraftment of neutrophils was successfully observed within 24 days of post-transplantation in all patients. All patients achieved complete chimerism at the time of engraftment. Two patients who underwent BMT from MRD and one patient who underwent BMT from MUD showed the gradual decrease of donor-derived cells. Donor lymphocyte infusion treatment successfully achieved the complete chimerism or stable mixed chimerism in these 3 patients. Although 3 patients experienced the acute GVHD (Grade I-II), the addition of glucocorticoids to tacrolimus prevented the extension of acute GVHD. Only one patient developed mild chronic GVHD presenting limited type of skin involvement. All patients are alive for 9 months to 9 years after HSCT with no signs of severe infections or transplantation-related morbidity. Our results demonstrate that BMT together with a sufficient immunosuppressive conditioning regimen may be a feasible and effective treatment for SCN patients, irrespective of initial engraftment failure. Although our results through the small number of cohort is limited to conclude, the BMT with the optimal donors may lead to the increased opportunity for lower risk of SCN patients especially at younger age as a curative treatment. The further analyses of accumulated cases are necessary to assess the efficacy, safety, and less late adverse effects related to HSCT including fertility. Disclosures No relevant conflicts of interest to declare.

scholarly journals ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN FANCONI ANEMIA; A SINGLE CENTRE EXPERIENCE

2021 ◽  
Vol 71 (1) ◽  
pp. 190-95
Author(s):  
Tariq Azam Khattak ◽  
Muhammad Farhan ◽  
Tariq Ghafoor ◽  
Tariq Mehmood Satti ◽  
Qamar Un Nisa Chaudhry ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Bone Marrow Transplant ◽  
Fanconi Anemia ◽  
Marrow Transplant ◽  
Hematopoietic Stem

Objective: To determine the treatment outcome of Hematopoietic stem cell transplantation in Fanconi Anemia. Study Design: Case series. Place and Duration of Study: Armed Forces Bone Marrow Transplant Center, Rawalpindi, from Jan 2001 to Jun 2018. Methodology: Data of all Fanconi anemia patients who had fully HLA matched bone marrow transplant during this period was analysed for variables affecting the outcome in terms of overall survival. Those fanconi anemia patients who had myelodysplastic changes or acute myeloid leukemia were excluded. Results: Total 27 patients underwent fully HLA matched allogeneic bone marrow transplant for Fanconi Anemia. Mean age of patients at transplant was 12.12 ± 5.16 years. All patients at transplant were in aplastic phase. Conditioning was done with fludarabine 120mg/m2 , ATG 20 mg/kg and Cyclophosphamide at a dose of 20-40 mg/kg. Mean time to neutrophil engraftment was 12.3 ± 2.92days and for platelets 20 ± 10.3 days. Major posttransplant complications were neutropenic fever in 26 (96%), hypertension in 18 (66.6%), mucositis in 12 (44.4%), azotaemia in 8 (29.6%), gut toxicity in 7 (25.9%) and haemorrhagic cystitis in 5 (18.5%) patients. Four patients (14.8%) had acute graft versus host disease while 7 (26%) patients had chronic GVHD. Overall survival at 6 months, 1, 5 and 8 years was 67%, 63%, 59% and 55% respectively. While overall survival in patients transplanted at younger age (<11 years) was 81.8% compared to 37.5% in older age group (>11years) and was statistically significant (p-value = 0.03). Conclusion: Our study demonstrated...................

scholarly journals ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR ADULT PATIENTS WITH FANCONI ANEMIA.

2016 ◽  
Vol 8 ◽  
pp. 2016054 ◽  
Author(s):  
Hosein Kamranzadeh fumani ◽  
Mohammad Zokaasadi ◽  
Amir Kasaeian ◽  
Kamran Alimoghaddam ◽  
Asadollah Mousavi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Fanconi Anemia ◽  
Bone Marrow Failure ◽  
Term Survival ◽  
Hematopoietic Stem

Background & objectives: Fanconi anemia (FA) is a rare genetic disorder caused by an impaired DNA repair mechanism which leads to an increased tendency toward malignancies and progressive bone marrow failure. The only curative management available for hematologic abnormalities in FA patients is hematopoietic stem cell transplantation (HSCT). This study aimed to evaluate the role of HSCT in FA patients.Methods: Twenty FA patients with ages of 16 or more who underwent HSCT between 2002 and 2015 enrolled in this study. All transplants were allogeneic and the stem cell source was peripheral blood and all patients had a full HLA-matched donor.Results: Eleven patients were female and 9 male (55% and 45%). Mean age was 24.05 years. Mortality rate was 50% (n=10) and the main cause of death was GVHD. Survival analysis showed an overall 5-year survival of 53.63% and 13 year survival of 45.96 % among patients.Conclusion: HSCT is the only curative management for bone marrow failure in FA patients and despite high rate of mortality and morbidity it seems to be an appropriate treatment with an acceptable long term survival rate for adolescent and adult group.

Pregnancy after Allogeneic Hematopoietic Stem Cell Transplantation in Fanconi Anemia Patients: Multi-Institution Cases Report of Female Fertility Recovery

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 456-456
Author(s):  
Samir Kanaan Nabhan ◽  
Marco Bittencourt ◽  
Michel Duval ◽  
Manuel Abecasis ◽  
Carlo Dufour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Fertility Recovery

Abstract Introduction. Fanconi anemia (FA) is a rare autosomal recessive syndrome characterized by chromosome instability. Main clinical features include progressive bone marrow failure, skeletal defects, increased susceptibility to malignancy and reduced fertility. Moreover, most recipients of allogeneic hematopoietic stem cell transplantation (HSCT) suffer from secondary infertility owing to gonadal damage from myeloablative conditioning. We report a rare clinical situation of FA patients pregnancy after allogeneic HSCT. Methods. Retrospective analysis of transplanted FA female patients from 1982 to 2008. Five centers participated in this study on behalf of Aplastic Anaemia Working Party-EBMT. Medical records were reviewed and data collected on a standard case report form including detailed information on diagnosis, transplant procedure, gynecological and obstetrics follow-up. Results. Among 387 transplanted FA patients we identified 202 females who performed a HSCT with a median age of 10,5 years. Five patients became pregnant after the procedure and one of them, twice. They all had their FA diagnosis confirmed by chromosomal breakage test and a bone marrow aspirate with severe hypoplasia/aplasia. Median age at transplantation was 12 years (range 5–17 years). All patients received myeloablative conditioning regimens (cyclophosphamide with or without thoraco-abdominal irradiation) before a bone marrow transplantation, 4 patients from HLA matched sibling donors and 1 from unrelated donor. During follow-up, 4 patients presented signs of ovarian failure (amenorrhea, low levels of FSH/LH and high levels of estradiol). Apart from 1 patient who spontaneously recovered regular menses, the other three received hormonal replacement therapy (HRT) for this purpose. Pregnancy occurred from 3,5 to 17 years after transplant. One patient had an early interruption with a caesarian section at 27 weeks because of an imminent HELLP syndrome. Other pregnancies were uneventful. Among the newborns, there were no FA positive tests, no congenital anomalies and all of them had normal growth and development. Patients remain alive with a median follow-up of 12 years after transplantation with normal hematological status. Conclusion. Fertility recovery after HSCT can result from incomplete depletion of the ovarian follicle reserve. HRT should begin promptly to prevent the early and late unwanted effects related to oestrogen deficiency after HSCT. Recovery of normal ovarian function and a viable pregnancy, is a realistic possibility even in Fanconi anemia patients following allogeneic SCT.

scholarly journals Donor-Derived Myeloid Heme Oxygenase-1 Controls the Development of Graft-Versus-Host Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Chloé Spilleboudt ◽  
Virginie De Wilde ◽  
Philippe Lewalle ◽  
Ludovic Cabanne ◽  
Mathieu Leclerc ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Heme Oxygenase ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Heme Oxygenase 1 ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Graft-versus-host disease (GVHD) remains a major clinical drawback of allogeneic hematopoietic stem cell transplantation (HSCT). Here, we investigated how the stress responsive heme catabolizing enzyme heme oxygenase-1 (HO-1, encoded by HMOX1) regulates GVHD in response to allogeneic hematopoietic stem cell transplantation in mice and humans. We found that deletion of the Hmox1 allele, specifically in the myeloid compartment of mouse donor bone marrow, promotes the development of aggressive GVHD after allogeneic transplantation. The mechanism driving GVHD in mice transplanted with allogeneic bone marrow lacking HO-1 expression in the myeloid compartment involves enhanced T cell alloreactivity. The clinical relevance of these observations was validated in two independent cohorts of HSCT patients. Individuals transplanted with hematopoietic stem cells from donors carrying a long homozygous (GT)n repeat polymorphism (L/L) in the HMOX1 promoter, which is associated with lower HO-1 expression, were at higher risk of developing severe acute GVHD as compared to donors carrying a short (GT)n repeat (S/L or S/S) polymorphism associated with higher HO-1 expression. In this study, we showed the unique importance of donor-derived myeloid HO-1 in the prevention of lethal experimental GVHD and we corroborated this observation by demonstrating the association between human HMOX1 (GT)n microsatellite polymorphisms and the incidence of severe acute GVHD in two independent HSCT patient cohorts. Donor-derived myeloid HO-1 constitutes a potential therapeutic target for HSCT patients and large-scale prospective studies in HSCT patients are necessary to validate the HO-1 L/L genotype as an independent risk factor for developing severe acute GVHD.

ASXL1 mutations in GATA2-Deficiency Correlate with Leukemic Transformation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 405-405
Author(s):  
Robert R. West ◽  
Amy Hsu ◽  
Katherine R. Calvo ◽  
Jennifer Cuellar-Rodriguez ◽  
Steven M. Holland ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Poor Overall Survival ◽  
Hematopoietic Stem ◽  
Gata2 Deficiency ◽  
Primer Sets

Abstract Abstract 405 Background: Recently, monoallelic mutations in the zinc-finger transcription factor GATA2 have been shown to be responsible for GATA2-deficiency, a syndrome characterized by opportunistic infections, frequently atypical mycobacterial infections or MAC, and a hypocellular myelodysplastic syndrome (MDS) that transforms into acute myelogenous leukemia (AML). GATA2-deficiency was previously known by several other names: MonoMAC (Monocytopenia and Atypical Mycobacterial Infection), DCML (Dendritic Cell Monocyte, Lymphoid Deficiency), Familial MDS/AML, or Emberger syndrome (lymphedema with monosomy 7). Heterogeneous genetic defects in GATA2 result in haploinsufficiency in both spontaneous and familial forms of the disease. Predicting the transformation from MDS to AML in GATA2-deficiency has clinical implications for both prognosis and the timing of hematopoietic stem cell transplantation. ASXL1, a gene related to the Drosophilia additional sex combs gene, encodes a chromatin binding/transcription repressor protein that is frequently mutated in MDS/AML. Mutations in ASXL1 are associated with reduced time to progression to AML and poor overall survival, independent of IPSS score. Methods: We sequenced the critical region of the ASXL1 gene in 20 patients with GATA2- deficiency to determine the frequency of ASXL1 mutations, and to correlate the presence of ASXL1 mutations with hematopoietic transformation. Since the ASXL1 mutations described in hematopoietic malignancies are located within the coding sequence of the two 3Õ-terminal exons (COSMIC: Catalogue of Somatic Mutations in Cancer), this ∼4.3kb region of ASLX1 was amplified by PCR and sequenced using five overlapping primer sets with substrate DNA isolated from mononuclear cell and granulocyte cell preparations from peripheral blood or bone marrow aspirates, or from extracts prepared from unfixed, unstained bone marrow aspirates. Mutations were confirmed with at least two independent PCR reactions with two unique primer sets. Results: Somatic ASXL1 mutations were detected in 8 of 20 patients with GATA2 mutations, 19/20 of whom had MDS. Five of these ASXL1 mutations have been previously associated with MDS/AML, including four independent cases of the most frequently described ASXL1 mutation (G646fs*12insG). The other four mutations were found once each; two of these were previously unreported (G652S(G>A) and L817fs*1delT). The patient cohort included two sisters with the same germline GATA2R398W mutation, but different somatic ASXL1 mutations (G464fs*12insG and R693X(C>T)). ASXL1 mutations were found in 4/5 GATA2- deficiency patients whose MDS had transformed into chronic myelomonocytic leukemia (CMML). Overall survival was lower for GATA2-deficiency patients with ASXL1 mutation (50% survival) compared to patients without ASXL1 mutation (83% survival), and was independent of IPSS score. Conclusions: ASXL1 is frequently mutated in patients with GATA2-deficiency with at least 40% of patients having a mutation in ASXL1 compared to a 10–15% mutation rate reported for all MDS/AML patients. ASXL1 mutation correlates with the development of CMML and with poor overall survival, as reported previously for MDS/AML patients. There was no correlation between the presence and type of ASXL1 mutation and the specific GATA2 mutation: the eight different ASXL1 mutation events were found in six different GATA2 mutant backgrounds. These results are directly relevant to the prognosis and the timing of hematopoietic stem cell transplantation for GATA2-deficiency. Disclosures: No relevant conflicts of interest to declare.

Low Counts Of Natural Killer Cells CD56 bright CD16 negative After Engraftment Are Associated With Worse Survival In Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4625-4625
Author(s):  
Matheus Vescovi Gonçalves ◽  
Mihoko Yamamoto ◽  
Eliza Y. S. Kimura ◽  
Vergilio Antonio Renzi Colturato ◽  
Maura Valerio Ikoma ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Natural Killer Cells ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Natural Killer ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Hematopoietic Stem ◽  
Related Mortality

Background Natural Killer Cells are innate immune system cells important in host defenses against viruses and tumor cells. Two subpopulations are well described: NK CD56bright CD16neg (NK56++16-, lower frequency on peripheral blood-PB, high cytokine production) and NK56dim16pos (NK56+16+, higher frequency on PB, high cytotoxic activity). They are activated through a balance between signals given from activating and inhibitory receptors (KAR and KIR, respectively). The ligands of KIRs are the MHC molecules and in the absence of compatible MHC, NK cells are activated. In the allogeneic hematopoietic stem cell transplantation (HSCT), recent studies showed that NK cells recovery is important on infection control and, in the presence of a KIR-MHC mismatch, they may be important on graft versus host disease (GVHD) and graft versus leukemia effects. However few studies evaluated NK subpopulations recovery and HSCT endpoints. Objectives To evaluate the impact of NK subpopulations recovery on HSCT endpoints: relapse, GVHD, non-relapse mortality and overall survival. Patients and Methods NK (CD3-, CD56+) subpopulations (NK56++16- and NK56+16+) were quantified by multiparametric flow cytometry at 9 sequential time points (before conditioning, at engraftment, and at days 3, 7, 14, 21, 60, 100 and 180 after engraftment). Overall, 111 patients, from 4 HSCT centers (65% male, median age 17 years, range 1-74), receiving bone marrow (BM, 46%), umbilical cord (UCB, 32%) or peripheral blood (PB, 22%) from unrelated (n=90) or related donors (n=21) were studied. The most common diagnosis was acute leukemia (AML 36%, ALL 31%, MDS 9%, CML 9%, Aplastic anemia 8%). Most patients received myeloablative conditioning (MAC) regimens (60%). Antithymocyte globulin (ATG) was used in 44 patients (40%) and total body irradiation (TBI) in 56 (51%). Median follow up time was 14 months (range 4-35). Results Eighty-six patients presented sustained allogeneic recovery (no differences among sources). Of these, median time to neutrophil engraftment was 18 days (range: 8-52). The cumulative incidence (CI) of non-relapse-related mortality (NRM) was significantly higher in those with lower counts of NK56++16– during first 3 weeks after HSCT (34% at 1 year for patients with less than 30 cells/uL at day 21 vs 11% for patients with higher counts, p=0.03). Overall survival was significantly worse in patients with lower counts of NK56++16- subpopulations in the day 21 after engraftment (86% at 1 year vs 54% for patients with less than 30 cells/uL – p=0.003). CI of grade II-IV acute GVHD and relapse were not significantly affected by NK counts. The number of NK56+16+ cells did not affect any endpoint studied. Cell source, age and conditioning regimen did not affect any of the NK subpopulations counts. In multivariate analysis, NK56++16- counts lower than 30 cells/uL at 21 and 60 days after engraftment remain an independent risk factor for non relapse mortality [HR: 4.8, CI (95%): 1.2-18.8]. Conclusions Low NK56++16- counts in the first weeks after HSCT are associated with increased non relapse related mortality, but not acute GVHD or relapse. The mechanisms that rules the NK56++16- role on immunity deserve further investigations. Disclosures: No relevant conflicts of interest to declare.

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