Surgery Treatment and Pathological Results of Patients of Malignant Hematological Disorders Complicated with Lung Diseases.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4107-4107
Author(s):  
Xiaowen Tang ◽  
Haoyue Huang ◽  
Shenghua Zhan ◽  
Xingwei Sun ◽  
Xiaolan Shi ◽  
...  
Keyword(s):  
Lung Diseases ◽  
Pulmonary Infection ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Granulomatous Inflammation ◽  
Antifungal Prophylaxis ◽  
Pulmonary Complications ◽  
Pathological Examination ◽  
Pathological Changes ◽  
Hematopoietic Stem

Abstract Abstract 4107 Objectives To determine the pulmonary pathological changes in patients of hematological malignancies with pulmonary complications using surgical or thoracoscopic technologie. Methods 17 hematological malignant patients who underwent surgical treatment were evaluated retrospectively in our study. Pulmonary infection was presented in 14 cases following chemotherapy, and lesions can not be completely absorbed after a broad-spectrum anti-bacterial and anti-fungal treatment. Furthermore, computerized tomographic scanning showed that there remained several kinds of localized lesions. Subsequently, all the 17 patients underwent open lung or thoracoscopic biopsies (lobar, partial, or wedge resection). The pathological changes of all the surgical specimens were examined postoperatively by standard hematoxylin and eosin staining. Results Pathological examination confirmed: Aspergillus infection in 9 patients, sub-acute inflammation (fibrosis and hematoma formation) in 3 patients, pulmonary infarction with granulomatous tissue in the periphery in 1 patient, granulomatous inflammation with calcified tubercle in 1 patient, alveolar dilation and hemorrhage, interstitial fibrosis and focal vasculitis in 1 patient, intercostal neurilemmoma in 1 patient, and moderate-differentiated adenocarcinoma accompanied by intrapulmonary metastasis in 1 patient. And several operative complications (1 case of fungal implantation, 3 cases of pleural effusion and adhesions and 2 cases of pulmonary hematoma) were occurred. The coincidence rate of pre- and post-operative diagnosis was 9/14 (64.3%). After surgery, 8 patients were received hematopoietic stem cell transplantation (HSCT, allo-gene or autologous), in which 7 cases were succeeded. Following the effective secondary antifungal prophylaxis,4 of 5 patients of aspergillosis were succeeded in transplantation free from mycotic relapse,just one patient was dead from fungal relapse. Conclusion Hematological malignancies with certain pulmonary complications, that is, persistent and/or medical-management-resistant pulmonary infection, hemoptysis, or lung diseases of diagnosis unknown, should be treated in time by surgical resection to effectively eliminate the residual disease and to achieve definitive diagnosis, so as to create a prerequisite condition for the following treatments. Moreover, the secondary antifungal prophylaxis could provide positive roles in protecting patients scheduled for chemotherapy and/or HSCT. Keywords hematological malignancies; immunocompromise; pulmonary aspergillosis; pulmonary resection; histopathology ; secondary antifungal prophylaxis Disclosures: No relevant conflicts of interest to declare.

scholarly journals Invasive Fungal Disease Following Myeloablative Cord Blood Transplantation for Patients with Hematological Malignancies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5653-5653
Author(s):  
Duihong Li ◽  
Huang Jiafu ◽  
Xiaofan Li ◽  
Zheng Jing ◽  
Haiying Fu ◽  
...  
Keyword(s):  
Cord Blood ◽  
Incidence Rate ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Stem ◽  
Blood Transplantation

Objective: Invasive fungal disease (IFD) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, limited data is available on its clinical features after cord blood transplantation (CBT) for patients with hematological malignancies. Method: We retrospectively reviewed 63 patients who underwent myeloablative CBT at our institution between July 2013 and June 2019 with a median follow-up of 14 months. Micafungin, Voriconzole or Posaconazole was used for IFD prophylaxis. Results: Eight patients were identified as having an IFD, including 2 with proven IFD, 1 with probable IFD, and 5 with possible IFD. The most common prophylaxis regimen is micafungin (68.2%, 43/63). The incidence rate of IFD in the primary antifungal prophylaxis (PAP) and secondary antifungal prophylaxis (SAP) groups were 11.3% and 25% (P=0.488). The OS of day at +100, six months and +200 in the IFD and No IFD groups were 62.5% vs. 86.9% (P=0.1), 50 % vs.78.2% (P=0.07), and 50% vs.75.9% (P=0.094), respectively. The 3-year probabilities of overall survival (OS) in the IFD and No IFD groups were 50% and 60.5%, respectively (p=0.316). The incidence rate of Non-relapse Mortality in the IFD and No IFD groups were 42.9% and 30%, respectively (p=0.319). Conclusion: Antifungal prophylaxis could help to reduce the incidence of IFD after CBT for patients with hematological malignancies. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals ANTIFUNGAL PROPHYLAXIS IN IMMUNOCOMPROMISED PATIENTS

2016 ◽  
Vol 8 ◽  
pp. e2016040 ◽  
Author(s):  
Lourdes Vazquez
Keyword(s):  
Gold Standard ◽  
Concomitant Medication ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Antifungal Drugs ◽  
Risk Of Infection ◽  
Scientific Societies ◽  
Hematopoietic Stem ◽  
Poor Efficacy

Invasive fungal infections (IFIs) represent significant complications in patients with hematological malignancies. Chemoprevention of IFIs may be important in this setting, but most antifungal drugs have demonstrated poor efficacy, particularly in the prevention of invasive aspergillosis. Antifungal prophylaxis in hematological patients is currently regarded as the gold standard in situations with a high risk of infection, such as acute leukemia, myelodysplastic syndromes, and autologous or allogeneic hematopoietic stem cell transplantation. Over the years, various scientific societies have established a series of recommendations for antifungal prophylaxis based on prospective studies performed with different drugs. However, the prescription of each agent must be personalized, adapting its administration to the characteristics of individual patients and taking into account possible interactions with concomitant medication.

Low Density Granulocytes in Patients after Allogeneic Hematopoietic Stem Cells Transplantation (allo-HSCT): A Distinct Class of Neutrophils in Systemic Alloimmunity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4614-4614
Author(s):  
Ekaterina Mikhaltsova ◽  
Valeri G. Savchenko ◽  
Larisa A. Kuzmina ◽  
Mikhail Drokov ◽  
Vera Vasilyeva ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Human Peripheral Blood ◽  
Unrelated Donor ◽  
Low Density ◽  
Hematopoietic Stem

Abstract Introduction It's generally considered that all alloimmune process such as acute graft-versus host disease (aGVHD) after allo-HSCT are mostly controlled by lymphocytes. The role of neutrophils in systemic alloimmunity after allo-HSCT is still illusive. In 1987 a distinct subset of proinflammatory, low-density granulocytes (LDGs) isolated from the peripheral blood mononuclear cell fractions of patients with system lupus erythematosus has been described. There is no LDG's in healthy donors. While the origin and role of LDGs still needs to be fully characterized, we try to describe this population in patients with hematological malignancies after allo-HSCT Patients and methods. Peripheral blood samples were collected in EDTA-tubes before allo-HSCT, on day +30,+60,+90 after allo-HSCT and at day of aGVHD from 47 patients with hematological malignancies (AML=22, ALL n=17, LPD=3, MDS =2; CML=2; 17 with active disease, 30 - in CR) after allo-HSCT (from matched unrelated donor n=34, from matched related donor n=13; MAC = 13, RIC=34). Isolation of mononuclear cells from human peripheral blood was made by standard protocol using Lympholyte®-M Cell Separation Media (Cedarlane Labs). The anti-CD66b-PE (Biolegend, USA) antibodies and FSC/SSC were used to determine LDGs cells as FSChigh \SSChigh \CD66b+. 100000 of cells were analyzed on a BD FACSCanto II (Becton Dickinson, USA). Results. Results of blood evaluation of 47 patients with hematological malignancies, whose blood was examined after allo-HSCT presented in table 1. Conclusion Despite the fact that we don't get significant differences. LDG's detection in allo-HSCT patients need further investigation. Table 1. Incidence of LDG after allo-HSCT in patients with and without aGVHD Table 1. Incidence of LDG after allo-HSCT in patients with and without aGVHD Disclosures No relevant conflicts of interest to declare.

A 5-Day Cytoreductive Chemotherapy Followed By Haplo-Identical HSCT (FA5-Bucy) As a Tumor-Ablative Regimen Improved the Survival of Patients with Advanced Hematological Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4674-4674
Author(s):  
Ting Yang ◽  
Jinhua Ren ◽  
Qiaoxian Lin ◽  
Xiaohong Yuan ◽  
Xiaofeng Luo ◽  
...  
Keyword(s):  
Complete Remission ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Severe Infection ◽  
Salvage Chemotherapy ◽  
Tumor Burden ◽  
Hematopoietic Stem ◽  
Entire Study ◽  
Gvhd Prophylaxis ◽  
Reduce Tumor Burden

Abstract Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. Patients and Interventions: We report the outcome of haplo-HSCT in 63 consecutive patients (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC), followed at our Center from 2/2013 to 12/2015. Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not (7%-98% BM blasts). No patient had severe infection or organ failure before HSCT. Patients received FA5-BUCY registered on http:// ClinicalTrials.gov (NCT02328950), i.e., 5-day salvage chemotherapy (Fludarabine/Ara-C) and conditioning (Busulfan/Cyclophosphamide). GvHD prophylaxis included ATG, CsA, MMF and short-term MTX. Results: All patients received stem cells from bone marrow and peripheral blood, and achieved successful engraftment, except two who died before. With a median follow-up of 269 days (120-1081), 42/63 patients are still alive and disease-free. Two-year OS and RFS were similar in patients not in remission and in those in complete remission (61.3% vs 56.3%, p=0.88; 58.3% vs 56.3%, p=0.991). Non-relapse mortality and relapse incidence were 22.2% and 11.1%, respectively. Severe acute-GvHD occurred in 4/63 patients. Transplant-related mortality was low at day+100 (17.5%) and for the entire study period (20.6%). Unexpectedly, few patients experienced mild-to-moderate toxicity, and main causes of death were infection and GvHD. BM blast counts, age,and donor-recipient gender-pairs did not affect the outcome. Less chemotherapy cycles prior to HSCT might result in more favorable outcome. Conclusions: Thus, haplo-HSCT with FA5-BUCY appears promising for advanced disease, especially when TBI and amsacrine, used for FLAMSA, are not available and in pediatric patients for whom TBI is not recommended. Two-year OS and RFS in patients not in remission prior to HSCT compared to those in complete remission. The two-year OS and RFS in patients not in remission were similar to those from patients in complete remission (61.3% vs 56.3%, p=0.88; 58.3% vs 56.3%, p=0.991). Two-year OS and RFS in patients not in remission prior to HSCT compared to those in complete remission. / The two-year OS and RFS in patients not in remission were similar to those from patients in complete remission (61.3% vs 56.3%, p=0.88; 58.3% vs 56.3%, p=0.991). Disclosures No relevant conflicts of interest to declare.

scholarly journals Palmitoyl Acyltransferase DHHC9 Is Required for Efficient Induction of Leukemia By Oncogenic NRAS

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 893-893
Author(s):  
Ping Liu ◽  
Bo Jiao ◽  
Ruihong Zhang ◽  
Huanbin Zhao ◽  
Chun Zhang ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Human Cancer ◽  
Lymphoblastic Leukemia ◽  
Myeloproliferative Disease ◽  
Ras Proteins ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Palmitoyl Acyltransferase

Abstract Hyperactivation of RAS is common in human cancer, including hematological malignancies. Since RAS proteins are difficult to target, identification of alternative means to block RAS oncogenic signaling is critical for developing therapies against RAS-driven cancer. The biological activity of RAS proteins relies upon post-translational modifications (PTMs) that anchor RAS to cellular membranes. Among RAS PTMs, palmitoylation is required for the high-affinity plasma membrane binding of NRAS, HRAS and KRAS4A. NRAS mutations are common in human hematological malignancies. We have previously shown that palmitoylation is essential for NRAS leukemogenesis, suggesting that targeting RAS palmitoylation may be an effective therapy for RAS related cancers. In previous studies, we blocked NRAS palmitoylation by mutating the palmitoylation site in NRAS. Therapeutic intervention of RAS palmitoylation requires targeting enzymes that mediate the modification reaction. Protein S-palmitoylation is catalyzed by the DHHC family of palmitoyl acyltransferases (PATs). Thus far 24 mammalian PATs have been identified. It has been shown that DHHC9 (a 364-amino acid protein encoded by ZDHHC9) is the ortholog of yeast Ras2 PAT and constitutes a mammalian PAT with specificity for H- and NRAS in vitro. Increased expression of DHHC9 has been found in various cancers. In this study we investigated the role of DHHC9 in normal hematopoiesis and NRAS leukemogenesis in vivo. We found that DHHC9 is not the only PATs for RAS palmitoylation in vivo and the Zdhhc9 knockout mice were born and grew similarly as the wild type mice. The frequency of lineage-specific populations and hematopoietic stem cell phenotypes were also similar in mice with knockout alleles of Zdhhc9 as that of wild type mice. However, loss of DHHC9 prolonged the survival of mice with myeloproliferative disease or T-cell acute lymphoblastic leukemia evoked by oncogenic NRAS expressed either from the endogenous locus or from retroviral promoter. These results demonstrate that DHHC9 is dispensable for normal hematopoiesis, but plays an important role in the pathogenesis of NRAS-induced leukemias. The findings suggest that palmitoyl acyltransferase DHHC9 may serve as a safe and effective target for developing therapies against NRAS-related cancers. Disclosures No relevant conflicts of interest to declare.

scholarly journals LB-ARHGDIB-1R As Novel Minor Histocompatibility Antigen For Therapeutic Application

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4465-4465
Author(s):  
Margot J Pont ◽  
Willemijn Hobo ◽  
M. Willy Honders ◽  
Simone A.P. van Luxemburg-Heijs ◽  
Michel G.D. Kester ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Hematopoietic Cells ◽  
Specific Lysis ◽  
Hematopoietic Stem ◽  
Therapeutic Relevance

Patients with hematological malignancies can be successfully treated with allogeneic hematopoietic stem cell transplantation (alloSCT). Beneficial Graft-versus-Leukemia (GvL) reactivity, however, is often accompanied with undesired Graft-versus-Host Disease (GvHD). In HLA-matched alloSCT, donor T-cells can mediate GvL reactivity by recognition of minor histocompatibility antigens (MiHA) on malignant cells, but also GvHD when MiHA are recognized on non-hematopoietic tissues. To decrease the incidence and severity of GvHD, T-cells can be (partially) depleted from the graft and re-administered later as donor lymphocyte infusion (DLI). MiHA are polymorphic peptides that are presented in HLA-molecules and can be recognized as non-self by donor-derived T-cells. Only a minority of MiHA have therapeutic relevance based on hematopoietic-restricted expression and only 25% and 40% of recipients transplanted with sibling and unrelated donors, respectively, are eligible for T-cell therapies in which one of the known hematopoietic-restricted MiHA is targeted. Therefore, to increase the efficacy and limit the toxicity of T-cell therapy, more therapeutic MiHA are needed. Recently, we identified a MiHA encoded by ARHGDIB, a gene that has been described to be highly expressed on hematopoietic cells, and we here studied the therapeutic relevance of LB-ARHGDIB-1R in detail. First, we confirmed hematopoietic-restricted expression of ARHGDIB by microarray gene expression analysis and demonstrated >10-fold overexpression in the majority of malignant and healthy hematopoietic versus non-hematopoietic cells. In line with its hematopoietic-restricted gene expression profile, LB-ARHGDIB-1R in the context of HLA-B* 07:02 was specifically recognized on different hematological malignancies, but not on non-hematopoietic fibroblasts and keratinocytes cultured in the absence or presence of IFN-γ, which was added to mimick the pro-inflammatory cytokine milieu of the early post-transplantation period. Next, we investigated the cytolytic capacity of LB-ARHGDIB-1R specific T-cells, and demonstrated specific lysis of patient, but not donor, EBV-B cells and specific lysis of an ALL sample in a 10 hrs 51Cr-release assay. Specific lysis of additional ALL and AML samples could be measured after 48 hrs of co-incubation in a flowcytometry-based cytotoxicity assay. To determine the in vivo immunogenicity of LB-ARHGDIB-1R, 11 MiHA-disparate HLA-B* 07:02 positive patient-donor pairs were screened for specific CD8+ T-cells by dual color tetramer analysis. All patients received partial T-cell depleted alloSCT and sampling was done at different time points after alloSCT (and DLI). In 4 out of 11 patients, LB-ARHGDIB-1R-specific T-cells (>0.01%) could be detected directly ex vivo and in 4 additional patients after 7 days of in vitro peptide stimulation, indicating that LB-ARHGDIB-1R is highly immunogenic. High frequencies of LB-ARHGDIB-1R specific T-cells were measured ex vivo in a patient whose hematological relapse was successfully treated with DLI, without development of GvHD, further supporting the therapeutic relevance of LB-ARHGDIB-1R. In summary, we confirmed hematopoietic-restricted expression of LB-ARHGDIB-1R and demonstrated T-cell mediated lysis of primary leukemic cells in long-term co-incubation assays. Furthermore, we showed that LB-ARHGDIB-1R is highly immunogenic and that specific T-cells could be detected in a patient who responded to DLI in the absence of GvHD. Altogether, our data support the clinical relevance of LB-ARHGDIB-1R as therapeutic MiHA with the potential to shift the delicate balance between GvL and GvHD in favor of a desired anti-tumor effect. Disclosures: No relevant conflicts of interest to declare.

Morbidity and Mortality Later Than 2 Years After HSCT. A Sinle Institution Experience.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4508-4508
Author(s):  
Hideki Akiyama ◽  
Wataru Munakata ◽  
Takeshi Kobayashi ◽  
Kazuhiko Kakihana ◽  
Takuya Yamashita ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Laboratory Data ◽  
Regular Insulin ◽  
Pulmonary Complications ◽  
Secondary Malignancy ◽  
Hematopoietic Stem ◽  
Renal Complication ◽  
Long Term Follow Up

Abstract Abstract 4508 Long-term follow-up data of the patients who underwent HSCT more than 2 years ago at a single institution in Japan was presented. The patients who received first allogeneic hematopoietic stem cell transplantation (HSCT) at Tokyo Metropolitan Komagome Hospital between January, 1990 and December, 2007 under hematology division were included. Follow-up data were obtained annually from the medical records if the patients visited our institution regularly. If the patients were not followed in our institution, follow-up data were requested to the hospitals where the patients had been followed or questionnaires were sent directly to the patients unless their addresses are not known. These letters were sent annually. The most recent laboratory data and any kind of complications under treatment including hypertension, hyperlipidemia, diabetes including usage of insulin, renal failure, dialysis, and any kind of malignancies were requested to be reported. Survival was the most primitive data and the reason of death was defined by one of the authors, HA. Chronic GVHD was excluded from the independent etiology of death. Progression of the disease or complications of the treatment for the progressive disease were considered to be due to relapse. The incidence of each complication was calculated using the number of the patients whose data are available. In total, 622 patients had received transplantation and 370 patients survived more than 2 years. During last two years, 211 patients had been followed in our institution while 74 patients by the institutions outside. Letters were sent directly to rest of surviving patients. As the result, 6 patients could not be reached by any method. Letters had been received without response in 15 patients. 72 patients died later than 2 years after transplantation. Relapse was the most important reason of death even more than 2 years after the transplantation. Although the incidence declined annually, the latest relapse was observed in the patient with CML almost 15 years after the transplantation. Pulmonary complications including bronchiolitis obliterans and infections followed. Secondary malignancy was the reason of death in 7 patients. Chronic kidney disease was already observed in 27 % of the patients who survived 2 years after transplantation and one of the devastating complications. In total of 7 patients needed to start regular dialysis or kidney transplantation and another 2 patients showed eGFR level of less than 15 ml/min/m2. Nephrotic syndrome was another renal complication observed in 4 patients. Hypertension was reported on 46/244 (19%) of the patients. Diabetes was reported on 27/241 (11.2%) and 13 of them were on regular insulin treatment. Definitive diagnostic criteria of diabetes were not indicated on this analysis suggesting higher incidence of glucose intolerance in these patients. There were 14 patients developed secondary malignancies diagnosed later than 2 years after transplantation and oral mucosa, tongue, esophagus and colon were the main organs involved. Physicians taking care of those patients were recommended to check kidney function and gastrointestinal tract including head/neck, esophagus and colon for secondary malignancy, as well as hematological status. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Extended Dosing Regimens for Fungal Prophylaxis

2019 ◽  
Vol 32 (3) ◽  
Author(s):  
Thomas Lehrnbecher ◽  
Konrad Bochennek ◽  
Thomas Klingebiel ◽  
Silke Gastine ◽  
Georg Hempel ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Hematological Malignancies ◽  
Antifungal Prophylaxis ◽  
Therapeutic Window ◽  
High Morbidity ◽  
Hematopoietic Stem ◽  
Invasive Fungal Diseases ◽  
Elimination Half ◽  
Dosing Regimens ◽  
Life Threatening

SUMMARY Invasive fungal diseases carry high morbidity and mortality in patients undergoing chemotherapy for hematological malignancies or allogeneic hematopoietic stem cell transplantation. In order to prevent these life-threatening infections, antifungal chemoprophylaxis plays an important role in daily clinical practice. Broad-spectrum antifungal triazoles are widely used but exhibit disadvantages such as relevant drug-drug interactions. Therefore, amphotericin B products or echinocandins can be an alternative in selected patient populations. As these compounds are available as intravenous formulations only, there is growing interest in extended dosing regimens. Although not approved for these agents, this strategy is a rational option, as these compounds have properties suitable for this strategy, including dose-proportional pharmacokinetics, prolonged elimination half-life, and a large therapeutic window. As the use of extended dosing regimens in antifungal prophylaxis is expanding in clinical practice, we reviewed the pharmacokinetic and pharmacodynamic rationale for this strategy, animal model data, dose escalation studies, and clinical trials supporting this concept.

scholarly journals Daratumumab and Venetoclax-Containing Regimens in the Management of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Hematological Malignancies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-9
Author(s):  
Fan Yang ◽  
Zhihui Li ◽  
Changwei Dong ◽  
Yang LEI ◽  
YanPing Geng ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Lymphoblastic Lymphoma ◽  
Hematopoietic Stem

Background: The prognosis of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies is poor with conventional therapies such as immunosuppressant withdrawal, interferon, chemotherapy, donor lymphocyte infusion and second allo-HSCT. Immunotherapy and targeted therapy may bring new hope for this setting. Objective: In current study, the safety and efficacy of daratumumab and venetoclax-containing regimens in the management of relapse after allo-HSCT in hematological malignancies were evaluated. Methods: From August 2019 to May 2020, 12 patients with hematological malignancies who relapsed after allo-HSCT were included. The median age was 26 (5-49) years old. The diagnosis included acute myeloid leukemia (AML, n=3), acute lymphoblastic leukemia (B-ALL, n=2), T lymphoblastic lymphoma/leukemia (T-LBL, n=6) and B lymphoblastic lymphoma/leukemia (B-LBL, n=1). The disease status before transplant was complete remission (CR) in 8 cases (minimal residual disease (MRD)+ in 4, MRD- in 4), partial remission (PR) in 1 case and recurrence in 3 cases. The types of transplant were haploidentical in 6 cases (50%), unrelated in 5 cases (41.7%) and matched sibling in 1 case (8.3%). Myeloablative conditioning regimens were used and GVHD prophylaxis was with cyclosporine, short-term methotrexate and mycophenolate mofetil. Anti-thymocyte globulin was applied in haploidentical and unrelated transplants. The median relapse time was 4 (1-10) months after HSCT and the pattern of relapse included hematologic relapse in 11 cases (91.7%), and MRD+ in 1 case (8.3%). The expression of CD38 antigen was detected by flow cytometry. Daratumumab (400mg for children, 800mg for adults at day 0 and 14) and venetoclax (50mg/d, gradually increased to 100-400mg/d, d1-28) were administrated for induction and consolidation therapies. Results After 1 cycle of induction therapy, 5 cases achieved CR (41.7%) (4/6 T-LBL, 1/3 AML), 1 case in PR (T-LBL, 8.3%), and 6 cases in non-remission (NR) (2/2 B-ALL, 2/3 AML, 1/1 B-LBL, 1/6 T-LBL, 50%). The median time to achieve CR was 26 (18-42) days. Three of 5 CR patients were treated with daratumumab and venetoclax only, and rest 2 CR patients were treated with daratumumab and venetoclax plus cytarabine (100mg/d for 3-5d) and etoposide (100mg/d for 3-5d). Four patients in CR were consolidated with daratumumab and venetoclax for continuous MRD- CR with the median 263 days(210,335) , while the rest 1 patient in CR underwent the second allo-HSCT.The median consolidation therapies was 2 (1-4) cycles and the interval was 8 weeks. With the median follow-up 236 (138-365) days, eight of 12 patients (66.7%) survived and DFS was 41.7%. Seven patients developed treatment-related neutropenia (58.3%) and 4 patients had infections (33.3%). No severe side effects were noted. No GVHD occurred during treatment with above regimens. Conclusion: Our pilot clinical study has shown that daratumumab and venetoclax-containing regimens are safe and effective in the management of relapse after allo-HSCT in patients with hematological malignancies. It seems that better response are in T-LBL. It may provide an option for the patients their leukemic cells expressing CD38 with or without chemotherapy-resistant diseases. [Key words] relapse; allogeneic hematopoietic stem cell transplantation; hematological malignancy; daratumumab; venetoclax Disclosures No relevant conflicts of interest to declare.

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