A novel risk model for predicting early relapse in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem-cell transplantation.

Relapse remains the leading cause of death in acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem-cell transplantation (allo-HSCT), limiting the efficacy of allo-HSCT. Thus, the ability to identify high-risk patients in a manner that permits early intervention has the potential to improve survival outcomes. We retrospectively enrolled 414 younger patients (aged 14-60 years) with AML who received allo-HSCT between January 2014 and May 2020. From June 2020 to June 2021, 110 consecutive patients were included prospectively in the validation cohort. The primary outcome was early relapse (relapse within 1 year). The cumulative incidence of early relapse after allo-HSCT was 11.8%. The overall survival rate for patients who relapsed within 1-year was 4.1% at 3 years after relapse. After multivariable adjustment, statistically significant associations between primary resistance, pre-transplantation measurable residual disease, DNMT3A mutation, or white blood cell count at diagnosis and early relapse were observed. An early relapse prediction model was developed based on these factors and the model performed well. Patients deemed to have a high risk or a low risk of early relapse had early relapse rates of 26.2% and 6.8%, respectively (P < 0.001). The prediction model could be used to help identify patients at risk for early relapse and to guide personalized relapse prevention.

Simplified MIPI-B prognostic stratification method can predict the outcome well-retrospective analysis of clinical characteristics and management of newly-diagnosed mantle cell lymphoma patients from China.

Mantle cell lymphoma (MCL) is an invasive B-cell lymphoma with significant individual differences. Currently, MCL international prognostic index (MIPI) score and tumor cell proliferation index Ki-67 have been proved to be the most important prognostic factors. But the prognostic effect of these factors in Asian population is uncertain. This study aimed to analyze the disease characteristics and prognostic factors of Chinese MCL patients.A total of 83 cases of newly-diagnosed MCL patients diagnosed by the Department of Pathology of our hospital between January 1, 2011, and May 31, 2016, were enrolled. The disease characteristics, treatment effects, and outcomes of the patients were collected and analyzed.According to our analysis, MCL cases accounted for 6.2% of non-Hodgkin lymphoma (NHL) cases and mainly occurred in elderly males. But the proportion of patients at stage IV by Ann Arbor staging system and high-risk group by simplified-MIPI (s-MIPI) were significantly lower than that among European patients. Immunochemotherapy containing rituximab was significantly more effective than chemotherapy (overall response rate, [ORR]: 88.5% vs 65.2%, P = .021) and significantly prolonged patient survival (progression free survival [PFS]: 45.5 m vs 16.2 m, P = .001; overall survival [OS]: 58.3 m vs 22.8 m, P = .001). The multivariate analysis showed that the B symptoms, s-MIPI and administration of immunochemotherapy were independent prognostic factors that affected PFS and OS of the patients. s-MIPI and B symptom make up s-MIPI-B stratification method, by which patients in low-risk group of s-MIPI without B symptom were classified as low-risk, patients in high-risk group of s-MIPI and patients in low-risk group of s-MIPI with B symptom as high-risk, the rest as middle-risk. 3-year PFS of the 3 groups were 74.9%, 43.4% and 16.1%, respectively (P = .001). 3-year OS were 84.4%, 62.2%, 27.6% (P <.001).Chinese MCL was male predominance. We have a minor proportion of late-stage and high-risk patients compared to European patients. Immunochemotherapy was proved to significantly improve the prognosis of MCL patients. B symptoms, s-MIPI, and administration of rituximab independently influenced the outcome. s-MIPI-B prognostic stratification method may better predict the prognosis of Asian MCL patients. Still, further confirmation in larger populations is needed.

Alteration of IFN-γ, IL-4, IL-17 and TGF-β levels in Serum of Patients with Chronic Lymphocytic Leukemia Treated with FCR / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the alteration and clinical significance of IFN-γ, IL-4, IL-17 and TGF-β levels in serum of patients with chronic lymphocytic leukemia treated with FCR.</p><p><b>METHODS</b>Forty-seven CLL patients treated with FCR regimen were enrolled in CLL group, meanwhile 30 healthy persons were selected in control group. The serum levels of IFN-γ, IL-4, IL-17 and TGF-β were detected by ELISA in CLL group before and after treatment and in control group, then the differences of IFN-γ, IL-4, IL-17 and TGF-β levels as well as IFN-γ/IL-4 ratio and TGF-β/IL-17 ratio were compared between 2 groups.</p><p><b>RESULTS</b>Before treatment with PCR regimen, the IL-4, IL-17 and TGF-β levels as well as TGF-β/IL-17 in CLL group were higher than those in control group (P<0.05), while the IFN-γ level and IFN-γ/IL-4 ratio in CLL group were lower than those in control group (P<0.05); after treatment with PCR regimen, the IL-4, IL-17 and TGF-β levels as well as TGF-β/IL-17 ratio all significantly decreased (P<0.05), while IFN-γ level and IFN-γ/IL-4 ratio significantly increased (P<0.05) as compared with those before treatment, moreover, the IL-4 and IL-17 levels as well as TGF-β/ IL-17 and IFN-γ /IL-4 ratio were no significantly different from those in control group (P>0.05), only the IFN-γ and TGF-β levels were significantly diffrent from control group (P<0.05). The analysis of Binet staging (stage A, B, C) showed that along with pregression of Binet stages, the TGF-γ/IL-17 levels as well as the IFN-γ/IL-4 ratio in CLL group negatively correlated with Binet staging (r=-0.53), while the TGF-β/IL-17 ratio positively correlated with Binet staging (r=0.46). The analysis of grouping accoraing to therapentic efficacy fonnd that the IL-4 and IL-17 levels and IFN-γ/IL-4 and TGF-β/IL-17 ratios in CR and PR groups were significantly different before and after treatment (P<0.05), while those in SD and PD groups did not showed statistical difference before and after treatment (P>0.05).</p><p><b>CONCLUSION</b>Along with the progression of disease, the IFN-γ/ IL-4 ratio gradually decreases, and the TGF-β / L-17 ratio gradually increases. The treatment with FCR regimen can overcome this tread, therefore dynamically monitoring the chages of IFN-γ/ IL-4 and TGF-β / L-17 ratios may contribute to guide the clinical treatment.</p>

Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years.

Invasive fungal infection (IFI) is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively reviewed the records of 408 patients undergoing allo-HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 (22.5%) episodes suffered proven or probable IFI (4 patients were proven, 88 patients were probable). Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen (HLA) mismatch, long-time neutropenia, and acute graft-versus-host-disease (GVHD) were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus (CMV) disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival (OS) rate for IFI was significantly lower than that of patients without IFI (41.9% vs. 63.6%, P<0.01).

Clinical characteristics and outcome of isolated extramedullary relapse in acute leukemia after allogeneic stem cell transplantation: a single-center analysis.

Isolated extramedullary relapse (EMR) of acute leukemia (AL) is a rare occurrence. However, it appears to be more common after allogeneic stem cell transplantation (allo-SCT). To characterize what has been observed in isolated EMR, we investigated 287 consecutive AL patients (144 acute myeloid leukemia; 138 acute lymphocytic leukemia; 5 acute mixed-lineage leukemia) who underwent allo-SCT. Twelve cases experienced relapse at extramedullary sites without concomitant involvement of the bone marrow (BM). The onset to relapse after allo-SCT was longer in extramedullary sites than in the BM (median, 10 months versus 5.5 months). EMR sites varied widely and included the central nervous system, skin, bone, pelvis and breasts. Univariate analysis demonstrated that cytogenetic abnormalities were correlated significantly with the onset of isolated EMR (P=0.001). The prognosis for patients who develop EMR remained poor but was relatively better than that after BM relapse (overall survival, 10 versus 18 months). Compared with local or single therapy, patients treated with systemic treatment in combination with local treatment could yield a favorable prognosis. In conclusion, we observed a significant number of isolated cases of EMR in AL patients after allo-SCT, cytogenetic abnormalities were correlated significantly with the onset of isolated EMR. We found that intensive approaches combining local and systemic therapy could produce favorable responses which may cure a proportion of these patients.

Role of CT-guided percutaneous lung biopsy in diagnosis of pulmonary fungal infection in patients with hematologic diseases.

The goal of our study is to evaluate the efficiency and safety of CT-guided percutaneous lung biopsy for the diagnosis of pulmonary fungal infection in patients with hematologic disease. Medical records were retrospectively reviewed for 16 patients with hematologic diseases, who were initially suspected to have pulmonary fungal infection clinically and underwent further diagnostic methods including blood culture, sputum culture and percutaneous lung biopsy. Of the 16 patients, 10 were diagnosed fungal infection (8 aspergillus, 2 mold fungus), 4 chronic organizing pneumonitis, 1 tuberculosis, and 1 Pneumocystis carinii through histological examination after percutaneous lung biopsy. However, the results of blood culture and sputum culture were negative. CT-guided biopsy showed 100% overall accuracy and 62.5% (10/16) fungal infection rate. The biopsy-induced complications encountered were pneumothorax in 3/16 (18.75%) and hemoptysis in 1/16 (6.25%). No serious complication was found in this series. In conclusion, CT-guided percutaneous lung biopsy is an effective and safe method for the diagnosis of pulmonary fungal infection in patients with hematologic diseases.

Candida tropicalis arthritis in a patient with acute leukemia.

Candida arthritis in patient with hematological malignancy is rare. A case of Candida tropicalis arthritis of knee occurred in a patient with acute monocytic leukemia was reported during the recovery phase of post chemotherapy myelosuppression and agranulocytosis. The patient was diagnosed as Candida tropicalis arthritis of knee according to the Candida tropicalis isolated from the synovial fluid. Itraconazole and amphotericin B were intravenously injected for therapy for 4 - 5 weeks based on the susceptibility test in vitro, which showed better efficacy. But the arthritis relapsed at 4 - 6 weeks after the drug withdrawal. The curative effect was found in patient after treatment with fluconazole injection and articular cavity douching with amphotericin B for 8 weeks. In conclusion, although Candida arthritis in patient with hematological malignancy is rare, it still occurred in the patient with hypoimmunity. The treatment emphasis showed be placed on the full dosage and full treatment course of antifungal agent.

[Study on unrelated donor allogeneic bone marrow transplantation with Bu-CY2 conditioning regimen for myelodysplastic syndrome].

OBJECTIVE: To evaluate the efficacy and safety of Bu-CY(2) conditioning regimen on allogeneic bone marrow transplantation (BMT) with unrelated donor for myelodysplastic syndrome. METHODS: Six patients received chemotherapy regimen of busulfan (Bu) and cyclophosphamide (CY) before allogeneic BMT (Bu 4 mg . kg(-1) . d(-1), -7 d - -4 d, CY 60 mg . kg(-1) . d(-1), -3 d - -2 d). Mycophenolate mofetil combined with cyclosporin A and methotrexate was used for prevention of acute graft-versus-host disease after transplantation. Lipo prostaglandin E(1)was used in prophylactic regimen for hepatic veno-occlusive disease. RESULT: Neutrophil count began to be higher than 0.5 x 10(9)/Lat the 18th day after BMT. Platelet count began to be higher than 20 x 10(9)/Lat the 21st day after BMT. Disease-free survival in the six patients was 27 months. CONCLUSION: Bu-CY(2) conditioning regimen on allogeneic bone marrow transplantation with unrelated donor is an effective therapy for patients with myelodysplastic syndrome.

[Mycophenolic acid induced apoptosis in T lymphocytic cells Molt-4 and its mechanism].

OBJECTIVE: To determine whether mycophenolic acid (MPA) exerts an apoptotic effect on human leukemic T cells Molt-4 and to elucidate its possible mechanism. METHODS: Cell morphology, DNA fragmentation, cell cycle,percentage of annexin V positive cells and enzymatic activity of caspase-3 were measured by microscopic, electrophoretic and flow cytometric techniques respectively. Human leukemic B cell line Raji was used as control. RESULT: MPA could induce apoptosis of Molt-4 cells with dose-and time-dependent manners; cells were blocked in the S phase. The activity of caspase-3 was enhanced in a dose-dependent manner in Molt-4 cells treated with MPA for 24 h. MPA could not induce apoptosis in Raji cells. CONCLUSION: MPA can induce apoptosis in Molt-4 cells which may be involved in the activation of caspase-3.

[A comparison of clinical outcomes between HLA allele matched and 1 - 2 alleles mismatched unrelated allogeneic bone marrow transplantations].

OBJECTIVE: To compare the clinical outcomes between HLA allele matched (HLA-M) and 1 approximately 2 alleles disparity mismatched (HLA-mis) unrelated allogeneic bone marrow transplantation (URD-BMT). METHODS: Thirty-nine patients received HLA-M and 21 received HLA-mis URD-BMT for the treatment of acute leukemia, chronic myeloid leukemia in chronic phase (CP) and myelodysplastic syndromes (MDS) in our hospital between November 1998 and December 2002. Conditioning regimen was Bu 16 mg/kg plus CTX 120 mg/kg, and mycophenolate mofetil (MMF), CsA and MTX were given to prevent aGVHD. RESULTS: Thirty-eight of the HLA-M group and 18 of the HLA-mis group were engrafted successfully. The median follow-up duration was 11 (2.5 - 52.0) months for HLA-M group and 9 (2 - 46) months for HLA-mis group. The 3-year probabilities of disease-free survival (DFS) for HLA-M and HLA-mis group were (79.2 +/- 7.1)% and (45.8 +/- 15.5)%, respectively (P < 0.05). Grade II - IV aGVHD occurred in 10 (26.3%) patients in HLA-M group and 6 (33.3%) in HLA-mis group, respectively (P > 0.05). CONCLUSION: URD-BMT is an effective modality for the treatment of leukemia and MDS. The outcome after URD-BMT can be optimized by matching the HLA-A, B and DR alleles between the donor and recipient.

[Treatment of childhood leukemia with unrelated donor allogeneic bone marrow transplantation].

OBJECTIVE: Allogeneic bone marrow transplantation has been established as a standard method for the treatment of a range of malignant and non-malignant hematologic diseases in children. Unfortunately, fewer than 30% of patients have a human leukocyte antigen (HLA)-matched sibling. Advances in our understanding of the HLA system and the development of large international donor registries encourage the increasing use of unrelated donors as an alternative source of stem cells. The purpose of this study was to evaluate the clinical efficacy and safety of unrelated donor allogeneic bone marrow transplantation (URD-BMT) for the treatment of childhood leukemia. METHODS: Six patients with leukemia received URD-BMT. Two of them suffered from chronic myeloid leukemia (CML), 3 suffered from acute lymphocytic leukemia (ALL) and 1 suffered from acute promyelocytic leukemia (APL) (CR2). All cases were facilitated by Tzu Chi Marrow Donor Registry (TCTMDR). The high resolution DNA test for classIand II was carried out in HLA typing of all donor-receiver pairs. HLA allele matched in three cases, mismatched with one locus in two cases and with two loci in one case. All patients were prepared with cyclophosphamide (CY) 60 mg/kg/day for 2 days (total dose 120 mg/kg) and busulfan (Bu) 1 mg/kg x 4/day for 4 days (total dose 16 mg/kg). Mycophenolate mofetil (MMF), CsA and MTX were given to prevent acute graft-versus-host-disease (aGVHD). CsA of 3 mg/kg/d was continuously given by i.v. infusion, and then 6mg/kg/d by oral. The blood CsA concentration was 200 - 300 ng/ml. MTX was given at the dosage of 15 mg/m(2) on d 1 and 10 mg/m(2) on d 3, 6,9 or 11. MMF was given at the dosage of 0.25 - 0.5 g/d from day 0 to day 120. Prostaglandin E1 was given to prevent the hepatic veno-occlusive disease (VOD), Ganciclovir was used to prevent CMV infection until the CMV antigenemia became negative. RESULTS: Analysis of DNA short tandem repeats showed total engraftment of donor marrow after transplantation in all cases. The median time when granulocyte exceeded 0.5 x 10(9)/L was 14.5 (13 - 18) days, platelets exceeded 20 x 10(9)/L was 16 (14 - 23) days. The acute GVHD grade II-IV occurred in 2 of 6 (33.3%) patients. There were 3 cases with chronic GVHD and none of them developed with the extensive chronic GVHD. All patients were alive in disease-free situation now with median follow-up 412 (187 - 1338) days. CONCLUSION: URD-BMT is an effective method for the treatment of childhood leukemia.