scholarly journals Preemptive interferon-α treatment could protect against relapse and improve long-term survival of ALL patients after allo-HSCT

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sining Liu ◽  
Xueyi Luo ◽  
Xiaohui Zhang ◽  
Lanping Xu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Multiparameter Flow Cytometry ◽  
Interferon Α ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival

AbstractRelapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Multiparameter flow cytometry and polymerase chain reaction assays were applied for MRD monitoring. Recombinant human IFN-α-2b injections were administered subcutaneously twice weekly in every 4 weeks cycle. Twenty-four (35.3%), 5 (7.4%), 6 (8.8%), and 13 (19.1%) patients achieved MRD negativity at 1, 2, 3, and > 3 months, respectively, after treatment. Seven patients showed grade ≥ 3 toxicities after IFN-α treatment. The 4-year cumulative incidence of total acute graft-versus-host disease (aGVHD), severe aGVHD, total chronic GVHD (cGVHD), and severe cGVHD after treatment was 14.7%, 2.9%, 40.0%, and 7.5%, respectively. The 4-year cumulative incidences of relapse and non-relapse mortality after treatment was 31.9% and 6.0%, respectively. The 4-year probabilities of disease-free survival and overall survival after IFN-α treatment were 62.1% and 71.1%, respectively. Thus, preemptive IFN-α treatment could protect against relapse and improve long-term survival for ALL patients who had MRD after allo-HSCT. The study was registered at https://clinicaltrials.gov as #NCT02185261 (09/07/2014).

Long-Term Survival In Patients With Acute Steroid Refractory Graft-Versus-Host-Disease (SR-GVHD) Treated With Infliximab Combined With Daclizumab

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4624-4624
Author(s):  
Sanaz Nicky Soltani ◽  
Ramaprasad Srinivasan ◽  
Theresa Jerussi ◽  
A. John Barrett ◽  
Thomas E Hughes ◽  
...  
Keyword(s):  
High Probability ◽  
Chronic Gvhd ◽  
Complete Response ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival ◽  
Post Transplant

Acute SR-GVHD occurs in approximately 15% of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), and is associated with a 70-90% long-term mortality rate. We previously reported that concomitant blockade of TNF-α and IL-2 pathways with infliximab combined with daclizumab have a synergistic therapeutic effect, with a high probability of complete resolution of SR-GVHD. Although various treatment modalities are effective in the treatment of SR-GVHD, minimal long-term follow up data exists for complete responders to second line treatments. Here we report long-term outcomes in a cohort of 23 subjects developing SR-GVHD treated with infliximab/daclizumab. A consecutive series of 141 patients with a variety of hematological and non-hematological malignancies as well as nonmalignant hematological disorders including severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria and pure red cells aplasia, underwent a reduced intensity allogeneic HSCT from an HLA identical or single antigen mismatched relative at a single institution between 2/2001 and 12/2008. Transplant conditioning consisted of cyclophosphamide (60 mg/kg days -7, -6) and fludarabine (25 mg/m2days -5 to -1) with or without equine ATG or 6-12 Gy of total body irradiation. GVHD prophylaxis was with cyclosporine with or without additional MMF or MTX. Twenty three patients (median age 35 years, range 13-65 years) developed SR-GVHD at a median of 28 days post transplant. SR-GVHD was defined as absence of response to at least 6 days of high dose methylprednisolone therapy. Following a diagnosis of SR-GVHD, patients received a combination of daclizumab (1mg/kg given on days 1, 4, 8, 15, 22), infliximab (10mg/kg given on days 1, 8, 15, 22), broad spectrum bacterial and anti-fungal prophylaxis, and had their methylprednisolone tapered to 1mg/kg/day. Combined cytokine blockade was highly active against SR-GVHD, with 21/23 (87.5%) patients achieving a complete response (CR), defined as total resolution of GVHD in all involved organ systems. All complete responders survived to hospital discharge. With a median follow-up of 9 years (range 5-10 years), 9/23 (39%) survive, including 6 patients without chronic GVHD whose immunosuppressive therapy (IST) has been discontinued and 3 patients with chronic GVHD (2 limited and 1 extensive) who continue to be tapered off IST. Fourteen of 21 patients with resolution of SR-GVHD died a median 173 days post transplant (range 67-1039 days), including 1 from complications related to recurrent SR-GVHD, 6 from progression of malignancy (all solid tumors), 2 from bleeding related to peptic ulcer disease and 5 from infectious complications including invasive fungal infection and CMV disease. A subgroup analysis showed 5/6 patients with SAA developing SR-GVHD had a complete response to combined infliximab/daclizimab. Remarkably, at a median 6 years follow up, 67% (4/6) of these SAA patients were long-term survivors. All these survivors have maintained normal blood counts and remained transfusion independent with 100% donor chimerism in myeloid and T-cell lineages. Conclusion Patients with SR-GVHD treated with infliximab combined with daclizumab had a high probability of achieving a complete response with nearly 40% of patients having long-term survival. This is the first report to show that long-term survival can be achieved in a substantial proportion of patients receiving combined IL-2 and TNF blockade for SR-GVHD. Disclosures: Off Label Use: Infliximab is FDA approved for the treatment of psoriasis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and ulcerative colitis. Daclizumab gained FDA approval for use in transplant rejection.

Achievement of Minimal Residual Disease Negativity By Multiparameter Flow Cytometry Is an Important Therapeutic Endpoint in Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia Receiving Salvage Treatment

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2916-2916 ◽  
Author(s):  
Nicholas J. Short ◽  
Hagop M. Kantarjian ◽  
Jeffrey L. Jorgensen ◽  
Farhad Ravandi ◽  
Musa Yilmaz ◽  
...  
Keyword(s):  
Research Funding ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Advisory Board ◽  
Multiparameter Flow Cytometry ◽  
Inotuzumab Ozogamicin ◽  
Term Survival ◽  
Minimal Residual

Abstract Background: Minimal residual disease (MRD) assessment by multiparameter flow cytometry (MFC) is prognostic for survival in newly diagnosed patients (pts) with acute lymphoblastic leukemia (ALL). The significance of achieving MRD negativity in the relapsed/refractory setting is less clear. Methods: Between 6/2010 and 5/2015, we identified 130 adult pts with relapsed/refractory B-cell ALL treated at our institution with either inotuzumab ozogamicin (n=75), blinatumomab (n=20) or mini-hyper-CVD plus inotuzumab ozogamicin (HCVD+InO; n=35) in either salvage 1 (S1; n=68) or salvage 2 (S2; n=62). MRD by MFC was assessed on remission bone marrow specimens at the time of achievement of CR/CRp/CRi. The MRD assay used a 15-marker, 6-color panel with a sensitivity of ≤0.01%. Results: Of the initial 130 pts, 78 (60%) achieved morphological response with a median time to response of 30 days (range, 13-99 days) and are the subject of this analysis. Of the 78 responding pts, 41 (53%) received inotuzumab, 11 (14%) blinatumomab, and 26 (33%) HCVD+ino. 46 pts (59%) were in S1 and 32 (41%) in S2. The median number of cycles to best response was 1 (range, 1-3). MRD negativity was achieved in 41 pts (53%). MRD negativity rates for pts in CR, CRp, and CRi were 57%, 53%, and 16%, respectively. Among pts who achieved remission, MRD negativity was achieved in 17 pts (41%) with inotuzumab, 8 (73%) with blinatumomab, and 16 (62%) with HCVD+InO (P=0.10). 26 pts (57%) in S1 and 15 (47%) in S2 became MRD-negative (P=0.40). The median follow-up duration was 27 months (range, 6-55 months). The median event-free survival (EFS) was 12 months in pts who achieved MRD negativity vs. 6 months in those who remained MRD-positive (P=0.09). The median overall survival (OS) was 17 months versus 9 months, respectively (P=0.18). Among pts in S1, achieving MRD negativity was associated with a longer EFS (median 18 months versus 7 months; 2-year EFS rate 46% versus 17%; P=0.06; Figure 1A) and OS (median 27 months versus 9 months; 2-year OS 52% versus 36%; P=0.15; Figure 1B). EFS and OS were similar in S2 regardless of MRD response. As expected, among pts who achieved MRD negativity, those in S1 had longer EFS (median 18 months vs. 5 months; P=0.001) and OS (median 27 months vs. 7 months; P=0.01) compared to those in S2. In contrast, for pts who remained MRD-positive, EFS and OS were similar regardless of salvage status (P=0.41 and P=0.39, respectively). In a 2-month landmark analysis of 64 pts, survival >2 years was observed in all groups of pts regardless of salvage treatment, salvage status or MRD status. 42 (66%) of the pts in this analysis underwent allogeneic stem cell transplantation (alloSCT). EFS and OS did not significantly differ between pts who did or did not undergo alloSCT, although a clear trend for improved long-term survival with alloSCT was observed. Among pts who achieved MRD negativity, the median EFS was 17 months and 12 months, and 2-year EFS rates were 46% and 28% for pts who underwent alloSCT vs. those who did not (P=0.24). The median OS was 24 months and 23 months, and 2-year OS rates were 55% and 46%, respectively (P=0.41). Pts who achieved MRD negativity after S1 treatment and then underwent alloSCT had the best outcomes. Of the 22 pts who achieved MRD negativity after S1 treatment, the median EFS for pts who underwent alloSCT (n=14) compared to those who did not (n=8) was not reached vs. 18 months, and the median OS was not reached vs. 27 months, respectively (P=0.28 for both). Among the 14 pts who achieved MRD negativity after S1 treatment and subsequently underwent alloSCT, 10 (71%) are still alive with a median follow-up of 24 months (range, 5-55 months). Conclusions: In patients with relapsed/refractory ALL, achievement of MRD negativity is associated with improved outcomes. Patients with relapsed/refractory ALL who achieve MRD negativity in S1 can achieve excellent long-term survival, especially if alloSCT is performed. Disclosures O'Brien: Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. DiNardo:Daiichi Sankyo: Other: advisory board, Research Funding; Novartis: Other: advisory board, Research Funding; Abbvie: Research Funding; Celgene: Research Funding; Agios: Other: advisory board, Research Funding. Jain:Genentech: Research Funding; Incyte: Research Funding; BMS: Research Funding; Celgene: Research Funding; Infinity: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Novimmune: Consultancy, Honoraria; Abbvie: Research Funding; Seattle Genetics: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Konopleva:Cellectis: Research Funding; Calithera: Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy.

Long-term survival in a randomized study of nonplatinum therapy versus platinum in advanced epithelial ovarian cancer

2007 ◽  
Vol 17 (5) ◽  
pp. 986-992 ◽  
Author(s):  
M. O. Nicoletto ◽  
S. Tumolo ◽  
R. Sorio ◽  
G. Cima ◽  
L. Endrizzi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Residual Disease ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Term Survival ◽  
Long Term Survival ◽  
Disease Free

The purpose of this study was to compare long-term survival in first-line chemotherapy with and without platinum in advanced-stage ovarian cancer. From July 1987 to November 1992, 161 untreated patients with FIGO stage III–IV epithelial ovarian cancer were randomized: 81 patients received no platinum and 80 received platinum combination. Residual disease after surgery was <2 cm in 61 patients without platinum, 59 with platinum. Median age was 58 years in nonplatinum arm and 55 years in platinum arm (range: 15–73). Complete and partial responses were 51% and 10% for nonplatinum arm and 51% and 8% for platinum arm, respectively (P= 0.7960). Stable disease was observed in 18% of patients in nonplatinum arm and 15% of patients in platinum arm and progression in 20% of nonplatinum- and 21% of platinum-treated cases. Ten-year disease-free survival was 37% for therapy without platinum and 31% for platinum combination (P= 0.5679); 10-year overall survival was 23% without platinum and 31% with platinum combination (P= 0.2545). Fifteen-year overall survival showed a trend of short duration in favor of platinum (P= 0.0678). Relapses occurred after 60 months in ten patients (seven with and three without platinum). The overall and disease-free survivals at 5, 10, and 15 years show no statistically significant long-term advantage from the addition of cisplatin; however, there is a slight trend in its favor.

scholarly journals Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment

Blood ◽  
2015 ◽  
Vol 126 (24) ◽  
pp. 2578-2584 ◽  
Author(s):  
Gerhard Zugmaier ◽  
Nicola Gökbuget ◽  
Matthias Klinger ◽  
Andreas Viardot ◽  
Matthias Stelljes ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Kinetics ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Term Survival ◽  
Long Term Survival ◽  
Disease Response ◽  
Key Points ◽  
Minimal Residual

Key Points Ten of 36 patients (28%) achieved an OS ≥30 months in a blinatumomab study in relapsed/refractory acute lymphoblastic leukemia. Long-term survival may be associated with T-cell expansion, B-cell depletion, and a minimal residual disease response.

Durable Engraftment and Long-Term Survival Following Fludarabine-Based Nonmyeloablative Hematopoietic Cell Transplantation (HCT) in Patients with ATG-Refractory Severe Aplastic Anemia (SAA) and Other Nonmalignant Hematological Disorders.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 252-252 ◽  
Author(s):  
Sakti Chakrabarti ◽  
Y. Takahashi ◽  
R. Srinivasan ◽  
I. Espinoza ◽  
T. Igarashi ◽  
...  
Keyword(s):  
T Cell ◽  
Hematopoietic Cell Transplantation ◽  
Bone Marrow Failure ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Term Survival ◽  
Long Term Survival ◽  
Hematological Disorders ◽  
Post Transplant

Abstract We evaluated the toxicity-profile, engraftment potential, and efficacy of fludarabine-based nonmyeloablative allogeneic HCT in patients with a variety of nonmalignant hematological disorders. Twenty three patients (median age 29 years; range 11–52) with nonmalignant hematological disorders including ATG refractory SAA (n=13), severe paroxysmal nocturnal hemoglobinuria (PNH: n=9), and pure red cell aplasia (PRCA; n=1) were transplanted from 5/99 – 8/2004 at the NHLBI. The majority of patients had an extensive transfusion history including 11/23 who had HLA allo-antibodies and 4/23 with allo-antibodies to RBCs. Conditioning with fludarabine (25 mg/m2 x 5 days), ATG (40mg/kg x 4 days) and cyclophosphamide (60mg/kg x 2 days) was followed by infusion of an un-manipulated G-CSF mobilized allograft from an HLA matched sibling (n=18), parent (n=2), or single antigen mismatched sibling (n=3). GVHD prophylaxis consisted of cyclosporine (CSA) either alone (n=2) or combined with mycophenolate mofetil (n=10) or mini-dose methotrexate (n=11). Despite a high prevalence of pre-transplant allo-immunization, all patients achieved sustained donor engraftment in both myeloid and T-cell lineages. Myeloid recovery (neutrophils >500cells/uL) occurred at a median 14 days post transplant (range 8–18 days). Conversion from mixed to full donor myeloid and T-cell chimerism occurred in all patients by 110 days post-transplant. CMV reactivation occurred in 11/21 patients at risk (KM probability 52%) without any cases of CMV disease. Grade II–IV and III–IV acute GVHD was the major transplant complication occurring in 13/23 (KM probability 60%) and 8/23 (KM probability 38%) patients respectively. Fourteen of 21 evaluable patients developed chronic GVHD (limited in 11 cases), which resolved completely with low-dose alternate day steroids and/or CSA in all but 1 case. One patient who received an allograft from his HLA matched father died 16 months post-transplant from complications related to chronic GVHD. With a median follow up of 25 months (range 1–64 months), 20/21 patients evaluable more than 100 days post-transplant survive in complete remission with full donor chimerism in all lymphohematopoietic lineages (KM probability of long-term survival 92.8 %-see figure ). Conclusion: Fludarabine-based nonmyeloablative transplantation achieves excellent donor engraftment and long-term disease free survival in heavily transfused and allo-immunized patients with ATG refractory SAA and other nonmalignant hematological disorders associated with bone marrow failure.

Comparative Survival of Haploidentical and Matched Related Hematopoietic Stem Cell Transplantation for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2591-2591
Author(s):  
Chen Huan ◽  
Kai-Yan Liu ◽  
Xu Lan-ping ◽  
Liu Dai-hong ◽  
Yu-hong Chen ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Transcript Levels ◽  
Long Term Survival ◽  
Imatinib Resistant ◽  
Donor Type ◽  
Related Group

Abstract Purpose The role of haploidentical related allogeneic hematopoietic stem cell transplantation (allo-HSCT) for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia( Ph+ ALL) is still not clear in the imatinib era, and limited data are available from the literature. We aimed to investigate the long-term survival between the haploidentical and matched related transplant in Ph+ ALL patients, and to analyze factors affecting relapse rate in different donor-type with maintenance therapy of imatinib post-transplant. Patients and methods The study population included Ph+ ALL patients receiving allo-HSCT from either haploidentical or matched related donor, and with maintenance therapy of imatinib post-HSCT. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were&gt;1.0 ± 109/L and platelet counts were&gt;50.0 ± 109/L, or if they displayed a high BCR-ABL transcript levels (∼10-2 after initial engraftment) or elevated BCR-ABL transcript levels in two consecutive tests. The imatinib treatment was scheduled for 3-12 months, or BCR-ABL transcript levels were negative at least for three consecutive tests and complete molecular remission was sustained for at least 3 months). Imatinib-resistant defined as: (1) transcript levels of BCR-ABL increased in two consecutive tests at least one-month interval; or (2) detection of point mutations in the BCR-ABL kinase domain (KD) after transplant. Results The total 120 consecutive Ph+ ALL patients received allo-HSCT and maintenance therapy of imatinib post-HSCT in our center between May 2005 to September 2012. Of these, 115 patients receiving a haploidentical (n=81) and matched related (n=34) graft were analyzed. 24 patients were identified as imatinib-resistant during post-transplant period, 13 in haploidentical group and 11 in matched related group. The 5-year cumulative incidence of relapse£¨CIR£©and non-relapse mortality (NRM) among the haploidentical group and matched related group were no different ( 18.2% vs.26.0%, p=0.212; 9.4% vs.7.2%, p=0.687). At a median follow-up of 37.5 months, the 5-year DFS and OS were 72.2% and 81.5% for the haploidentical group, compared with 68.5% and 79.5% for matched related group (p = 0.265, 0.419, respectively). Multivariate analysis showed that RT-PCR-BCR-ABL positive pre-transplant was significant factor for OS in haploidentical transplant (P=0.046). Remission status (&gt;CR1) at HCT was a significant predictor to CIR in matched related group (p=0.020), but it wasn't a significant factor to impact on CIR in haploidentical transplant group. Imatinib-resistant was a significant factor to affect DFS, OS and CIR in both donor-type groups. Conclusion In the imatinib era, haploidentical HSCT for Ph+ALL achieves identical long-term survival compared with matched related HCT. Remission status (&gt;CR1) at the transplant does not significantly impact on relapse in haploidentical transplant. Imatinib-resistant is a worse predictor to long-term survival and relapse rate in both donor-type group after HCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Colony-Stimulating Factor 3 Receptor M696T Mutated in a Patient with Ph+ Acute Lymphoblastic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Xin Chen ◽  
Bichen Wang ◽  
Aiming Pang ◽  
Erlie Jiang ◽  
Yajing Chu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Colony Stimulating Factor ◽  
Term Survival ◽  
Long Term Survival ◽  
Tumor Transformation ◽  
Stimulating Factor

Purpose: Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in a variety of myeloid disorders, such as severe congenital neutropenia (SCN), chronic neutrophilic leukemia (CNL), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and atypical chronic myelogenous leukemia (aCML). Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. We report a case of philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) with the M696T mutation in CSF3R gene and assess the pathogenicity of the CSF3R M696T mutation in Ph+ ALL. Experimental Design: Here we report on a 32-year-old female who presented with asthenia. The initial hematological workup revealed white blood cell (WBC) count of 97 x 109/L (normal range 4-10 x 109/L). There was 84% prolymphocyte in the bone marrow. The immunophenotype of the blasts as judged from flow cytometry was in accordance with a B-ALL. The fusion gene for BCR-ABL P210 was positive. Hot mutation closely related to diseases was: CSF3R (nucleotide change c.2087 T&gt;C, amino acid change p.M696T, mutation frequency 50.4%). Cytogenetic analysis showed 46, XX, t (9;22) (q34;q11). The patient was diagnosed as Ph+ ALL with the CSF3R M696T mutation and achieved Long-term survival after unrelated donor hematopoietic stem cell transplantation. Meanwhile we performed a series of experiments using murine interleukin 3 (IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T mutation. The phosphorylation of STAT3 was analyzed by G-CSF dependence assays and immunoblot analysis to evaluate the CSF3R M696T mutation contribution to the tumor transformation ability of Ba/F3 cells. Results: This patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor (TKI) and long-term survival by unrelated donor transplantation. We confirmed the presence of a CSF3R M696T germline mutation in this patient, and the mutation was inherited from her mother. The experiments in vitro result showed the CSF3R M696T mutation harbors marginal contribution to the tumor transformation ability of Ba/F3 cells. CSF3R M696T mutation was neutral in tumor transformation ability. Conclusions: We believe that TKI is still effective in patients with the CSF3R M696T mutation in Ph+ ALL. Donor with CSF3R M696T mutation might still be selected. Disclosures No relevant conflicts of interest to declare.

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