New allergies after cord blood transplantation

Background aimsUmbilical cord blood transplantation (CBT) is an effective treatment for benign and malignant diseases. Late effects of CBT are not well described in the literature. In the present study, we present our experience of new-onset allergies in long-term survivors after CBT.MethodsAfter an initial patient had a severe peanut allergic reaction after CBT, all CBT patients were prospectively followed for new allergy development. Fifty patients received CBT between March 2006 and June 2011.ResultsThe median follow-up after CBT was 447 days (range, 12–2022). At the time of analysis, 30 patients were alive, with 3-year survival of 55.5%; median follow-up of surviving patients was 910 days (range, 68–2022). The allergic syndrome developed in five patients, with the cumulative incidence of new allergies at 2 years of 18.4% (95% confidence interval, 10.8–26). The median time to onset of new allergy after transplantation was 298 days (range, 250–809).ConclusionsAllergy development has been linked to a delayed maturation of the immune system in several studies. We present the first case series of patients who had new allergies after CBT. Further study of this novel complication as well as counseling of patients after CBT would be important.     

Enfermedad fúngica invasora por hongos filamentosos en pacientes hematológicos

Invasive mould infections (IMI) are a persistent problem with high morbidity and mortality rates among patients receiving chemotherapy for hematological malignancies and hematopoietic stem cell transplant recipients. Management of IMI in this setting has become increasingly complex with the advent of new antifungal agents and diagnostic tests, which have resulted in different therapeutic strategies (prophylactic, empirical, pre-emptive, and directed). A proper assessment of the individual risk for IMI appears to be critical in order to use the best prophylactic and therapeutic approach and increase the survival rates. Among the available antifungal drugs, the most frequently used in the hematologic patient are fluconazole, mould-active azoles (itraconazole, posaconazole and voriconazole), candins (anidulafungin, caspofungin and micafungin), and lipid formulations of amphotericin B. Specific recommendations for their use, and criteria for selecting the antifungal agents are discussed in this paper.     

血液系统肿瘤患者侵袭性肺部真菌感染的外科手术治疗

目的探讨怀疑肺部有侵袭性真菌感染(invasivefungalinfection,IFI)的血液恶性肿瘤患者行手术切除肺部病灶的安全性及有效性。方法分析2005年4月～2009年7月之间因血液系统肿瘤合并疑似侵袭性肺部真菌感染而接受肺切除术的10名患者,总结术后并发症及死亡率来探讨手术的有效性和安全性。结果手术均在全身麻醉下进行,5例为胸廓切开术,5例为胸腔镜下手术。3例为病灶楔形切除术,7例为肺叶切除术。术后组织病理:确诊真菌感染6例(60%),慢性细菌感染1例,3例未见明确病原菌。术后4例出现并发症:3例为轻度并发症(30%),其中2例气胸后自行吸收,1例局限性肺不张;1例严重并发症为血胸(10%)。术后30d死亡率为10%。术后真菌复发率为16%。随访至2009年8月31日,中位随访时间为3.8个月(0.7～31.1个月),4例(40%)死亡,但手术相关死亡率为0%。结论手术切除不仅有助于明确诊断而且还可以清除病灶、防止IFI复发和允许进一步的免疫抑制治疗,手术本身是安全的。     

乳腺恶性血液病的病理类型、临床特点及生存分析

目的:探讨乳腺恶性血液病的病理分型、患者的临床特征及预后。方法:回顾性分析2014年1月至2019年1月空军军医大学西京医院收治的33例乳腺恶性血液病患者的病理分型、临床特征及预后。结果:33例患者中,32例为女性,1例为男性,平均年龄为45.5岁(12-78岁)。经病理确诊29例(29/33,87.9%)为非霍奇金淋巴瘤,其中弥漫大B细胞淋巴瘤(18/29,62.1%)最为常见,其次是NK/T细胞淋巴瘤(3/29,10.3%),B淋巴母细胞白血病/淋巴瘤(2/29,6.8%),而伯基特淋巴瘤、滤泡淋巴瘤、原发皮肤间变大细胞淋巴瘤各1例(1/29,3.4%),其余3例未进一步分型。此外,1例(1/33,3.0%)霍奇金淋巴瘤,3例(3/33,9.1%)急性白血病复发累及乳腺。原发性乳腺恶性血液病为19例(57.6%),继发性为14例(42.4%),病变主要累及右侧乳腺(18例,54.5%),其次为左侧(10例,30.3%),双侧均累及的为少数(5例,15.2%)。19例原发性乳腺恶性血液病均为淋巴瘤,与14例继发性乳腺恶性血液病相比,其血小板计数明显升高(P=0.004),β2-MG显著降低(P=0.049),B症状少(P=0.017),Ann Arbor分期主要为Ⅰ-Ⅱ期(P<0.01),骨髓受累少(P<0.01)等特点。生存分析提示原发性乳腺恶性血液病患者比继发性患者生存期更长(HR=9.846,P=0.002)。恶性血液病累及骨髓可导致生存期显著缩短(HR=6.434,P<0.01)。结论:乳腺恶性血液病患者以中年女性为主,原发性乳腺恶性血液病比继发性发病率高(分别为57.5%和42.5%),最常见的病理类型为弥漫大B细胞淋巴瘤,病变主要累及右侧乳腺。与继发性乳腺恶性血液病相比,原发性乳腺恶性血液病患者具有血小板计数相对更高,β2-MG水平更低,往往不伴B症状,Ann Arbor分期主要为Ⅰ-Ⅱ期,骨髓不受累,且生存期显著延长等特点。此外,恶性血液病累及骨髓提示预后不良。     

Invasive infections caused by Saprochaete capitata in patients with haematological malignancies: Report of five cases and review of the antifungal therapy

BackgroundSaprochaete capitata (formerly known as Geotrichum capitatum and Blastoschizomyces capitatus) is a ubiquitous fungus found in soil, water, air, plants and dairy products. It colonizes the skin, and bronchial and intestinal tract of healthy people producing serious opportunistic infections in patients with haematological malignancies, especially in those with acute leukaemia. Since 1960s its presence is being increasingly recognized in this group of patients. The clinical spectrum of S. capitata disseminated infections is very similar to that produced by Candida, being easily misinterpreted. The associated high mortality and low susceptibility to fluconazole and echinocandins of S. capitata require the acknowledgement of this emergent infection so that it can be properly treated.Case reportWe report 5 new cases of S. capitata disseminated infection in patients with advanced haematological malignancies observed in the haematology unit between the years 2004 and 2010, and review the state-of-the-art for diagnosis and treatment of this infection.ConclusionsBased on our experience, the prophylactic use of or the empirical antifungal treatment with fluconazole and/or echinocandins would not be adequate for oncohaematological patients in those hospitals where S. capitata infection may be highly prevalent.     

Anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia

Despite therapeutic advances, the long-term survival rates for acute myeloid leukemia (AML) are estimated to be 10% or less, pointing to the need for better treatment options. AML cells express the myeloid marker CD33, making it amenable to CD33-targeted therapy. Thus, the in vitro and in vivo anti-tumor activities of lintuzumab (SGN-33), a humanized monoclonal anti-CD33 antibody undergoing clinical evaluation, were investigated. In vitro assays were used to assess the ability of lintuzumab to mediate effector functions and to decrease the production of growth factors from AML cells. SCID mice models of disseminated AML with the multi-drug resistance (MDR)-negative HL60 and the MDR⁺, HEL9217 and TF1-α, cell lines were developed and applied to examine the in vivo antitumor activity. In vitro, lintuzumab significantly reduced the production of TNFα-induced pro-inflammatory cytokines and chemokines by AML cells. Lintuzumab promoted tumor cell killing through antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) activities against MDR⁻ and MDR⁺ AML cell lines and primary AML patient samples. At doses from 3 to 30 mg/kg, lintuzumab significantly enhanced survival and reduced tumor burden in vivo, regardless of MDR status. Survival of the mice was dependent upon the activity of resident macrophages and neutrophils. The results suggest that lintuzumab may exert its therapeutic effects by modulating the cytokine milieu in the tumor microenvironment and through effector mediated cell killing. Given that lintuzumab induced meaningful responses in a phase 1 clinical trial, the preclinical antitumor activities defined in this study may underlie its observed therapeutic efficacy in AML patients.     

Membrane-bound/soluble IL-2 receptor (IL-2R) and levels of IL-1α, IL-2, and IL-6 in the serum and in the PBMC culture supernatants from 17 patients with hematological malignancies

The present study investigated the peripheral blood mononuclear cells (PBMC) blastic responses to PHA, PHA plus recombinant IL-2 (rIL-2) and rIL-2 alone; the expression of membrane-bound IL-2R on PHA-stimulated PBMC; and the levels of IL-1α, IL-2, IL-6, and sIL-2R in serum and in culture supernatants from PHA-stimulated PBMC in 17 patients with hematological malignancies (mean age 58.5 yr, range 22–82): 6 with non-Hodgkin’s lymphoma (NHL), 4 with Hodgkin’s lymphoma (HL), 5 with Hairy cell leukemia, 1 with chronic myelogenous leukemia, and 1 with chronic lymphocytic leukemia. The patients with HL and NHL with active disease (AD) were separated from those in clinical remission. The patients with AD were studied at diagnosis (obviously before therapy) and the patients in clinical remission were out of therapy since at least 6 mo. The lymphocyte blastogenic response to PHA was significantly lower in patients with HL and NHL with AD than in the control group. The response to rIL-2 alone was in the same range in the control group and in HL and NHL AD patients. By adding rIL-2 to PHA there was an increase of the blastogenic response of the same patients. The percentage of CD25 expressed on PHA-stimulated lymphocytes from patients with HL and NHL AD and from normal subjects is in the same range. Serum levels of IL-2, IL-6, and sIL-2R were significantly higher in HL and NHL AD patients than in controls as well as in all other hematological malignancies. Supernatants derived from PHA-stimulated PBMC were assessed for the presence of cytokines and sIL-2R by ELISA. The levels of IL-2, IL-6, and sIL-2R were significantly lower in HL and NHL AD patients than in controls as well as in all other hematological malignancies.     

Cutaneous squamous cell carcinoma metastatic to chronic lymphocytic leukaemia: diagnostic potential of fine needle aspiration cytology

OBJECTIVE: The phenomenon of cancer-to-cancer metastasis of cutaneous squamous cell carcinoma (SCC) and chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL) is a rare event and only occasionally documented in the medical literature. METHODS: Two patients with SCC of the skin that were previously treated for CLL are presented. Both had palpable lymph nodes in the neck and fine needle aspiration cytology (FNAC) was performed to evaluate the pathological process. In addition, the literature on cutaneous SCC metastatic to CLL/SLL with special emphasis on the role of FNAC in this specific clinical situation was reviewed. RESULTS: On examination of the FNAC smear, cancer-to-cancer metastasis of cutaneous SCC to lymph node replaced by CLL was found. In one of the patients, light microscopy examination of the smear was complemented by immunostaining of atypical cells with cytokeratin antibodies and immunophenotyping of lymphoid cells by flow cytometry. In addition to our two patients, nine cases of cutaneous SCC metastatic to CLL/SLL have been reported in the literature, and in only one was the diagnosis made by FNAC. CONCLUSION: FNAC supported by ancillary immunocytological techniques could also be used in diagnosis of specific clinical situations such as cancer-to-cancer metastasis of the tandem of SCC-CLL/SLL.