Metachronous mixed cellularity classical Hodgkin’s lymphoma and T-cell leukemia/lymphoma: A case report

BACKGROUND The development of peripheral T-cell lymphoma(PTCL)after chemotherapy for Hodgkin’s lymphoma(HL)is rare,and highly aggressive TCL/leukemia has not been reported to date.The relationship between HL and PTCL needs further exploration to understand the pathogenesis of metachronous lymphoma(ML)and find effective treatment options.We report a patient with ML,whose biopsy of a right cervical lymph node initially confirmed classical HL(CHL).CASE SUMMARY We report a patient with ML,whose biopsy of a right cervical lymph node initially confirmed CHL,with typical reed–sternberg cells expressing CD30 and PAX-5.T-cell leukemia/lymphoma occurred 3 years after treatment,and a lymph node biopsy at the onset confirmed PTCL,nonspecific type,expressing CD3,CD4 and CD8.The patient was treated with standard doses of chemotherapy,programmed cell death-ligand 1 monoclonal antibody,and chidamide,all of which failed to achieve complete remission.The patient was diagnosed with refractory state,and eventually died of leukocyte stasis.CONCLUSION The accuracy of the diagnosis needs to be confirmed when chemotherapeutic drugs are not effective.

Adult T-cell leukemia/lymphoma presenting multiple lymphomatous polyposis

Multiple lymphomatous polyposis (MLP) is an unusual form of non-Hodgkin's lymphoma characterized by polyps throughout the gastrointestinal tract. It has been reported that most MLP are observed in cases with mantle cell lymphoma of B-cell type. We herein present a case of a 66-year-old man with adult T-cell leukemia/lymphoma (ATLL). Colonoscopy revealed MLP throughout the colon and histopathological findings of ATLL cell infiltration. The patient died despite combination of chemotherapy. The literature of manifestations of colonic involvement of ATLL isreviewed and the importance of endoscopic evaluation to differentiate ATLL intestinal lesions from opportunistic infectious enterocolitis is discussed.

ESTABLISHMENT OF CELL CLONE OF LYMPHOMA AND A CELL LINE INFECTED WITH LEUKEMIA VIRUS AND STUDY ON ITS INDUCTED DIFFERENTIATION

Since 1960, the tumor strains of L6565 viral leukemia, SRS lymphoma and L783 transplantable leukemia were established successively in our laboratory. Recently, derived from the strains of threse leukemia/lymphoma, SRS-82 cell line, SACIIB2, SACIIC3 cell clones and a cell line infected with SRS leukemia virus (SRSV/3T3) were obtained at vitro. The main results of study on the biology, virology and Its Induction of differentiation are summarily reported.

THE ULTRASTRUCTURAL STUDY OF NON－HODGKIN＇S LYMPHOMA CELL，CHRONIC LYMPHOCYTIC AND HAIRY CELL LEUKEMIA

Non-Hodgkin’s lymphoma cell leukemia (NHLCL),chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HLC) are the diseases very similar to each other. The differential diagnosis is very difficult,especially when there are small lymphoid cells in Periphcral blood and bone marrow under light microscope. We have observed 34 cases with electron microscope. The studies were correlated with clinical manifestation, cytology, pathology and immunologic histochemistry. Ultrastructural features strongly indicated the difference in three various diseases, although all the immunologic markers showed B-cell type.It is concluded that electron microscopic examination is of a definite significance in the diaguosis and successful treatment.

Post-Therapy Profile of BMI-for-Age of Indian Survivors of Pediatric Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma

Background: Obesity in pediatric ALL survivors is a well recognized late effect. Hence the present study examines the BMI-for-age of Indian childhood ALL and NHL survivors. Method: A retrospective study of 118 ALL/NHL survivors and 138 age sex matched was carried out. From the recorded heights and weights were body mass index (BMI) was computed. The survivor data was compared with 138 controls from the data set collected by investigators previously. Results: 82.8% of patients had BMI-for-age in 5th-84th percentile (healthy) at time of diagnosis and at inclusion in the study. Comparison of BMI of survivors with matched controls was not significant. However, The mean BMI-for-age for younger patients (3 to 12 years) was significantly higher than mean BMI-for-age of matched controls. Distribution of data by time elapsed from therapy was significant. Overweight/obesity was observed among the survivors who were off therapy for two years with increase in after four years post-therapy. Conclusion: Our preliminary study indicates late effects of therapy and points to the need of long term assessment of the survivors, even though majority of them were within the normal weight range.

Differences in Treatment Patterns and Health Care Costs among Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia Patients Receiving Rituximab in the Hospital Outpatient Setting versus the Office/Clinic Setting

Objective: To examine whether differences in treatment patterns and health care costs exist among chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL) patients receiving rituximab in a hospital outpatient setting versus those receiving rituximab in a physician office/community clinic setting. Methods: This retrospective database study used medical and pharmacy claims (1/2007-7/2012) from a large US health plan. Patients ≥18 years with ≥2 rituximab claims and ≥2 claims for either NHL or CLL were identified. The date of the first rituximab claim were set as the index date, and differences in treatment patterns and health care costs were examined during the period following the index date. Costs were adjusted for patient characteristics using a multivariate regression model. Results: A total of 4441 patients were identified;3167 received rituximab in the office/clinic setting, and 1274 in the hospital outpatient setting. From 2007 to 2012, the percentage of patients receiving rituximab in the hospital outpatient setting increased from 22% to 39%. Patients treated in the hospital outpatient setting vs. the office/clinic setting had fewer average counts of rituximab infusions (5.60 vs. 7.49, p 0.001), higher total health care costs (cost ratio = 1.325, p 0.001), higher infusion day drug and administration costs (cost ratio = 1.509, p 0.001), and higher rates of ER visits and inpatient stays (both p 0.001). Conclusions: These findings suggest that site of care may impact treatment patterns and costs of patients receiving rituximab, and additional research is needed to better understand the reason(s) for these differences by site of service.

Graft vs host disease impacts overall survival post allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia/lymphoma

AIM To examine the outcome and prognostic factors for high risk patients with acute lymphoblastic leukemia/lymphoma(ALL/LBL) who underwent allogeneic hematopoietic stem cell transplantation(HCT) at our center during the period of2010-2017 METHODS After due institutional review board approval, patients with high risk ALL/LBL post HCT were identified and included. All records were retrospectively collected. Time to event analysis was calculated from the date of HCT until event of interest or last follow up with Kaplan-Meir means. Cox regression model was used for multivariable analysis calculation.RESULTS A total of 69 patients were enrolled and examined with a median age of 21(14-61). After a median follow up of 15 mo(2-87.3), the 2-year cumulative incidence of relapse, cumulative incidence of non-relapse mortality, progression free survival and overall survival(OS) were 34.1%, 10.9%, 54.9% and 62.8%,respectively. In a multivariable analysis for OS; acute graft vs host disease(GVHD) and chronic GVHD were significant with corresponding hazard ratio 4.9(1.99-12; P = 0.0007) and 0.29(0.1-0.67; P = 0.0044), respectively.CONCLUSION Allogeneic-HCT for high risk ALL/LBL resulted in promising remissions particularly for patients with cGVHD.

Secondary peripheral T-cell lymphoma and acute myeloid leukemia after Burkitt lymphoma treatment:A case report

BACKGROUND Multiple primary cancer refers to more than one synchronous or sequential cancer in the same individual.Multiple primary cancer always presents as solid cancer or acute myeloid leukemia(AML)secondary to lymphoma.Here,we report a rare case of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment.CASE SUMMARY A 54-year-old female patient was admitted to our hospital complaining of edema on her left lower limb.Physical examination revealed multiple superficial lymphadenectasis on her neck and pelvis.Color ultrasonography examination showed multiple uterine fibroids and a solid mass at the lower left side of the abdomen.Pathological biopsy revealed Burkitt lymphoma.After three hyper-CVAD(A+B)regimens,she achieved complete remission.Two years later,lymphadenectasis reoccurred.A relevant biopsy confirmed the diagnosis of peripheral T-cell lymphoma,which was accompanied by gastrointestinal invasion and hemocytopenia.Meanwhile,bone marrow examination revealed AML.On the second day of scheduled treatment,she developed gastrointestinal bleeding,peptic ulcers,and hemorrhagic shock and was critically ill.She was then discharged from the hospital due to financial concerns.CONCLUSION This is the first report of secondary peripheral T-cell lymphoma and AML after Burkitt lymphoma treatment with heterochronous and synchronal multiple primary cancers.

Two Cases of Tuberculosis Manifesting as Cutaneous Solitary Mass in Patients with Adult T-Cell Leukemia/Lymphoma

Tuberculosis (TB) is a major public health problem worldwide and a large number of fatal cases are still reported. Immunocompetent individuals are naturally susceptible to TB, and immunocompromised patients have a greater risk of infection. Although patients with adult T-cell leukemia/lymphoma (ATL) are in an immunosuppressed condition, there is only one reported case of TB accompanied with ATL in the English- language literature in the field of dermatology. Here, we report two patients with chronic-type ATL infected with TB manifesting as cutaneous solitary masses. Case 1 was a 58-year-old woman diagnosed with lumbar abscess with pulmonary TB. Case 2 was an 84-year-old woman diagnosed with tuberculous lymphadenitis in the left cervical region. It is important to raise the differential diagnosis of TB and perform tissue culture for acid-fast bacilli as well as Interferon-Gamma release assay test when dermatologists encounter mass lesions in patients with ATL.

Chronic lymphocytic leukemia/small lymphocytic lymphoma complicated with skin Langerhans cell sarcoma:A case report

BACKGROUND Langerhans cell sarcoma(LCS)is a rare malignancy with poor prognosis.LCS and chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma(SLL)can occur in the same diseased tissues,such as lymph nodes or skin.CASE SUMMARY A 48-year-old female Han Chinese patient was admitted for generalized lymph node enlargement for 6 years and abdominal distension for 1 wk.She was diagnosed with small B-cell lymphoma(stage IV)/CLL(Benet stage B)and received chemotherapy.She started oral ibrutinib in February 2019.She was hospitalized on June 11,2019,and a 1.5 cm×1.5 cm dark-red nodule with ulceration scalp lesion was found.Biopsy revealed LCS but without CLL/SLL.She was diagnosed with CLL/SLL(Binet stage C,Rai stage IV)accompanied by secondary histiocytic sarcomas and skin LCS and received cyclophosphamide,doxorubicin,vincristine,dexamethasone,and etoposide but developed severe cytopenia.She ultimately refused treatments and discharged spontaneously.She died on September 12,2019.The literature review showed that in patients with CLL/SLL,skin lesions of LCS are accompanied by CLL/SLL.This patient was different from the previously reported cases of skin LCS in patients with CLL/SLL.CONCLUSION In this patient,the skin lesion of LCS showed no concomitant CLL/SLL.

Coexistence of diffuse large B-cell lymphoma,acute myeloid leukemia,and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient:A case report

BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.

Acute myelomonocytic leukemia and T-lymphoblastic lymphoma as simultaneous bilineage hematologic malignancy treated with decitabine:A case report

BACKGROUND Simultaneous bilineage hematologic malignancies are rare;however,several cases of acute myeloid leukemia(AML)and T-lymphoblastic lymphoma(T-LBL)cooccurrence have been reported.A standard treatment for simultaneous AML and T-LBL has not yet been established,and its prognosis is very poor.Further studies to develop standard treatments are required to increase patient survival rates.CASE SUMMARY A 69-year-old man complaining of pleuritic chest pain visited the emergency room.Computed tomography revealed multiple enlarged lymph nodes(LNs)in the neck and groin and pulmonary thromboembolism with pulmonary infarction.Furthermore,a peripheral blood smear performed due to leukocytosis revealed circulating blasts.Acute myelomonocytic leukemia(AMML)was diagnosed after bone marrow examination,and T-LBL positivity for terminal deoxynucleotidyl transferase,cluster of differentiation(CD)34,and CD4 was confirmed by cervical LN biopsy.Decitabine and dexamethasone were administered because he could not receive intensive chemotherapy due to poor performance status.Complete remission of AMML and T-LBL was achieved after 4 cycles of decitabine plus dexamethasone.CONCLUSION We report the therapeutic effect of decitabine,a hypomethylating agent(HMA),in patients with concurrent bilineage hematologic malignancies and suggest that further studies are required to evaluate the therapeutic effect of HMAs on both lymphoid and bilineage hematologic malignancies.

Expression of the B-Cell Lymphoma/Leukemia 11A Gene in Malignant Hematological Cell Lines through Quantitative Reverse Transcription Polymerase Chain Reaction

The B-cell lymphoma/leukemia 11A （BCL11A） gene is essential for normal lymphoid development and has been associated with hematological malignancies. In the current study, the relative expression level of BCL11A in malignant hematological cell lines was evaluated through real-time quantitative reverse transcription polymerase chain reaction （qRT-PCR）. METHODS The relative expression level of BCLllA mRNA in malignant hematological cell lines was determined through qRT- PCR using SYBR Green I dye. Glyceraldehyde-3-phosphate dehydro- genase was used as the reference gene to confirm the relative expression level of BCL11A gene mRNA. RESULTS The relative expression level of BCL11A mRNA in cell lines from B-cell malignancies was significantly higher compared with that from acute rnyeloid leukemia （P 〈 0.05）. Different cell lines with malignant B-cells exhibited a wide range of BCL11A expressions ranging from 27.37 to 93.38. CONCLUSION The overexpression of BCL11A gene mRNA in malignant B-cells might play a role in B-cell lymphoma/leukemia.

全身磁共振成像在血液系统肿瘤中的诊疗进展

血液系统肿瘤作为多病灶的全身性肿瘤,早期病灶筛查和诊断对治疗和预后至关重要。全身磁共振成像(whole-body magnetic resonance imaging,WB-MRI)作为一种无电离辐射、软组织分辨率高的全身成像技术,对血液系统肿瘤早期病变,包括微小病灶和转移病灶的检测具有优势,已逐步应用于血液系统肿瘤的早期筛查、诊断分期、治疗反应评估及复发预测等方面。本文就WB-MRI在血液系统肿瘤,包括多发性骨髓瘤(multiple myeloma,MM)、淋巴瘤和白血病中的诊疗及预后进展予以综述,并分析这三种血液系统肿瘤在WB-MRI上的异同点,探讨机器学习和深度学习技术在WB-MRI的应用,旨在为临床诊治血液系统肿瘤和今后的研究提供参考。

T-ALL来源的骨髓基质细胞通过FGF2-FGFR2通路促进T-ALL增殖

目的探究骨髓基质细胞(BM-MSCs)对急性T淋巴细胞白血病(T-ALL)影响的作用机制,寻找靶向BMMSCs的有效治疗策略。方法构建Notch-1过表达诱导的T-ALL小鼠模型,分选T-ALL中BM-MSCs,与T-ALL细胞系建立体外共培养系统,检测共培养后T-ALL增殖能力变化。运用RNA测序技术寻找不同来源MSCs的差异表达基因,并用PCR验证。在小鼠体内注射BGJ398,检测肿瘤生长情况。结果与T-ALL来源的MSCs共培养后,T-ALL细胞的增殖能力显著增加。RNA测序结果显示,T-ALL来源的MSCs成纤维细胞生长因子2(FGF2)分泌增加,与TALL细胞上的成纤维细胞生长因子2受体(FGFR2)结合可激活T-ALL细胞中PI3K/AKT/mTOR信号通路。加入BGJ398阻断FGF2和FGFR2之间的相互作用可以抑制小鼠T-ALL肿瘤的生长。结论BM-MSCs可通过FGF2/FGFR2通路促进T-ALL肿瘤生长,阻断FGF2/FGFR2通路是克服BM-MSCs介导T-ALL进展的有效策略。

A case of mucosa-associated lymphoid tissue lymphoma of the gastrointestinal tract showing extensive plasma cell differentiation with prominent Russell bodies

A 73-year-old Japanese woman was hospitalized for detailed examination of nausea, diarrhea and loss of appetite. Atypical erosion in the ileum was found on endoscopy. Biopsy of this erosion showed proliferation of cells containing numerous Russell bodies. Differential diagnoses considered were Russell body enteritis, crystal-storing histiocytosis, Mott cell tumor, immunoproliferative small intestinal disease(IPSID) and mucosaassociated lymphoid tissue(MALT) lymphoma. The cells containing prominent Russell bodies showed diffuse positivity for CD79 a and CD138, but negative results for CD20, CD3, UCHL-1, CD38 and CD68. Russell bodies were diffusely positive for lambda light chain, but negative for kappa light chain, and immunoglobulin(Ig)G, Ig A and Ig M. Based on these findings, Russell body enteritis, crystal-storing histiocytosis and IPSID were ruled out. As the tumor formed no mass lesions and was restricted to the gastrointestinal tract, MALT lymphoma with extensive plasma cell differentiation was finally diagnosed. The patient showed an unexpectedly aggressive clinical course. The number of atypical lymphocytes in peripheral blood gradually increased and T-prolymphocytic leukemia(T-PLL) emerged. The patient died of T-PLL 7 mo after admission. Autopsy was not permitted.

Papular mycosis fungoides: Six new cases and association with chronic lymphocytic leukemia

Papular mycosis fungoides(MF) is a rare presentation of MF. Six illustrative cases of papular MF were retrospectively reviewed. Five of the cases studied by immunohistochemistry had variable numbers(range: 1%-20%) of CD30+ cells in the dermal infiltrate, a finding that is characteristic of lymphomatoid papulosis but may occasionally occur in typical early MF. Although none of our papular MF patients had progressive disease, lesions with relatively high numbers of CD30+ cells in 3 patients did not respond well to skin-directed treatments used for MF. Interestingly, these patients had evidence of coexisting clonal B cell populations in the blood(one with clonal B cell lymphocytosis and two with B-cell chronic lymphocytic leukemia). We conclude that:(1) papular MF may contain CD30+ cells, thereby causing confusion with lymphomatoid papulosis; and(2) papular MF, like more typical MF, may be associated with clonal B-cell proliferations including chronic lymphocytic leukemia.

Prognostic Significance of Apoptosis Regulators in B-Cell Chronic Lymphocytic Leukemia

Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL. The study aimed to clarify the prognostic role of MCL-1, BCL-2 and BCL-2/ Bax ratio in B-CLL. Patients & method: Estimation of MCL-1, BCL-2 and Bax expressions by a flow cytometry in 45 B-CLL patients and the prognostic value of these markers were correlated with other well-known established prognostic markers and treatment response. Results: MCL-1 was expressed in 60% of cases while BCL-2 was expressed in 82.2% of cases. MCL-1 expression was significantly high in male gender, short lymphocyte doubling time (LDT), and high expression of CD 38 (p β2M, CD38 expression), low ZAP-70 expression, splenomegaly and higher Rai stage were significantly increased in patients with high expression of BCL-2 (p β2M, high C-D38 expression, low ZAP-70 expression, the poor cytogenetic and splenomegaly in patients with high expression of BCL-2/ Bax ratio (p In conclusion: MCL-1, BCL-2 expressions and BCL-2/Bax ratio could be useful potential predictive and prognostic markers in B-CLL.

Sudden extramedullary and extranodal Philadelphia-positive anaplastic large-cell lymphoma transformation during imatinib treatment for CML:A case report

BACKGROUND Chronic myeloid leukemia(CML)is a malignant hematologic malignancy that can progress to blast phase with a myeloid or lymphoid phenotype.Some patients with CML can also progress to blast crisis phase;however,the transformation of CML into Philadelphia-positive lymphoma is extremely rare.CASE SUMMARY We present a patient with CML who experienced a sudden transformation to anaplastic large-cell lymphoma(ALCL)after 7 mo of treatment with imatinib,during which she had achieved partial cytogenetic response as well as early molecular response.The patient noticed a mass in her left shoulder,the biopsy data of which were consistent with ALCL;moreover,her lymphoma cells exhibited BCR-ABL gene fusion.The patient was diagnosed with Philadelphia-positive ALCL that progressed from CML,and was thus treated with the second generation tyrosine kinase inhibitor nilotinib.Six months later,the mass had totally disappeared and the BCR-ABL fusion gene was undetectable in the peripheral blood.To our knowledge,this is the first patient known to have developed Philadelphia-positive ALCL transformed from CML.CONCLUSION Unexplained lymphadenopathy or an extramedullary mass in a patient with CML may warrant a biopsy and testing for BCR-ABL fusion.

儿童急性早幼粒细胞白血病治疗后继发T淋巴母细胞淋巴瘤1例临床报告

目的总结急性白血病治疗后继发非霍奇金淋巴瘤患儿的临床诊治过程,探讨疾病相关机理。方法回顾性分析1例急性早幼粒细胞白血病(APL)治疗后继发T淋巴母细胞淋巴瘤(T-LBL)患儿的临床资料,并检索急性白血病治疗后继发非霍奇金淋巴瘤的文献报告进行总结。结果患儿,男,10岁,因“间断发热”起病,确诊APL后,在治疗过程中出现骨髓复燃,调整治疗方案后达完全缓解,然而在结束白血病治疗后因淋巴结肿大诊断为T-LBL,经规范化疗再次得以缓解。检索近10年文献,急性白血病治疗后继发非霍奇金淋巴瘤共报告9例,均为成人病例,其中6例患者至报告时均为无病生存状态。结论急性白血病治疗后继发非霍奇金淋巴瘤的发生率低、预后较好。此外,对肿瘤性疾病化疗后的患者,需注意继发性肿瘤的发生,应用先进检测技术可提高对继发性肿瘤致病机制的认知。