Successful treatment of disseminated Trichosporon beigelii (cutaneum) infection with associated splenic involvement

Fungemia caused by Trichosporon beigelii (cutaneum) has been recently recognized as a fatal infection afflicting immunocompromised patients. The authors report the case of a leukemic patient who developed splenic infection from disseminated T. beigelii. Treatment with amphotericin B, 5-fluorocytosine, and splenectomy proved successful. The etiology of disseminated T. beigelii infection, visceral seeding, and combination antifungal therapy also are discussed.     

Systemic mycosis due to Trichosporon cutaneum: a report of two additional cases

Two additional cases of systemic mycosis due to Trichosporon cutaneum are reported and are compared with the previously published case of Rivera and Cangir. Both patients (a four-year-old male and a 57-year-old female) had acute leukemia for which they were receiving chemotherapy, and both presented with fever that was unresponsive to conventional antibiotics. Both had positive blood cultures for Trichosporon cutaneum. The disease was further documented in the four-year-old male by renal biopsy and by bone marrow culture; he was treated with apparent success with amphotericin B. However, the 57-year-old female died shortly after the begining of similar treatment, and autopsy demonstrated involvement of the left kidney, spleen, bone marrow, and liver. The organism in both these cases, as well as the case of Rivera and Cangir, exhibited both hyphal and yeastlike forms in tissue sections. We believe that the therapeutic success in the case of the four-year-old male was primarily related to his remission from leukemia.     

Relationship between human T cell leukemia virus-II and atypical hairy cell leukemia: a serologic study of hairy cell leukemia patients

Human T cell leukemia virus (HTLV-II) is an infrequently encountered human T cell leukemia virus first isolated from a patient with atypical hairy cell leukemia. Recently, we identified a second patient infected with HTLV-II who had a similar clinical syndrome of atypical hairy cell leukemia associated with peripheral T cell lymphocytosis. HTLV-II was detected by molecular hybridization studies, and more recently, by electron microscopy, in cell lines derived from the patient. Both patients came from the Los Angeles area and had spent several years in Alaska. As opposed to our two patients, 21 patients with more typical cases of hairy cell leukemia were seronegative for HTLV-II. Two additional cases of unusual T cell malignancy linked to HTLV-II have been described by other investigators and bear limited similarity to our index cases. Further studies are necessary to define the spectrum of malignancies linked to HTLV-II and to identify infected individuals for prospective study.     

Chemoprophylaxis of bacterial infections in granulocytopenic patients with ciprofloxacin

The trial was conducted to evaluate the antimicrobial prophylactic efficacy of ciprofloxacin in reducing the frequency of infections in granulocytopenic patients. The frequency of infections was evaluated in 34 patients with acute non-lymphoblastic leukemia, acute lymphoblastic leukemia, blast crisis of chronic myelogenous leukemia and other malignancies. 46 courses of oral prophylactic treatment with 500 mg ciprofloxacin twice daily were administered. While there was no infection in 61% of treatment courses, fever over 38 degrees C (axillary) occurred in 39%. 6 patients had a fungal pulmonary infection, one patient a supposed viral pneumonia, and only two patients had a documented bacterial infection. There were no severe side effects. We conclude that ciprofloxacin is a potent drug in prophylaxis of bacterial infections in cancer patients with therapy-induced granulocytopenia.     

单倍型供者淋巴细胞输注治疗复发性急性白血病

 目的　探讨难治性复发性急性白血病单倍型淋巴细胞输注的疗效。方法　2006年4月至2007年10月应用单倍型淋巴细胞输注治疗复发性急性髓性白血病（AML）3例（M2 2 例,M4 1例）,复发性急性淋巴细胞白血病（ALL）1例,4例复发患者在二线方案化疗无效后,采集供者淋巴细胞,子女供父母3例,母供子1例,供者淋巴细胞在输注前,患者再次接受了不同方案的化疗,白细胞较低时输注供者的淋巴细胞,平均输注细胞2.3（1.4～3.1）×108／kg,输注前淋巴细胞接受了6～8 Gy 60Coγ射线照射。结果　3例AML患者1例获得了完全缓解（CR）,2例有效,1例ALL无效。4例患者输注单倍型供者淋巴细胞后无移植物抗宿主病的发生,未出现严重的骨髓抑制,1例患者发生了带状疱疹病毒感染。结论　单倍型供者淋巴细胞输注配合化疗对难治复发的AML有疗效,输注细胞的数量及照射的剂量需进一步探讨。     

Allogeneic marrow transplantation for acute non-lymphoblastic leukemia in relapse using fractionated total body irradiation

Twenty-three patients with acute non-lymphoblastic leukemia in relapse were treated with cyclophosphamide, fractionated total body irradiation (200 rad/day for six days) and allogeneic marrow transplantation. Six patients are alive in remission 756–1306 days following transplantation. One patient died of infection on day 17 without evidence of engraftment; all others achieved sustained engraftment. Eight patients died of recurrent leukemia, four of interstitial pneumonitis, two of infection, one of veno-occlusive disease of the liver and one of cardiac failure. The median survival time was 181 days.     

急性白血病伴CD56阳性的临床意义

目的：探讨CD56在急性白血病中的表达及其临床意义。方法：就近2年来应用流式细胞仪检测了CD56的92例急性白血患者中发现的CD56阳性病例,分析细胞形态学、免疫表型和临床特点。结果：92例急性白血病中15例（16．3％）表达CD56,其中1例急性前髓系／NK细胞白血病（Myeloid/NK cell precursor acute leukemia),1例原始NK细胞白血病（Blastic NK cell leukemia),1例NK样T细胞淋巴瘤／白血病（NK－like T-cell lymphoma/leukemia),12例急性髓细胞白血病伴NK细胞抗原表达或急性髓系／NK细胞白血病。结论：伴CD56阳性急性白血病,其细胞形态学、免疫表型及临床表现各有特点,见于M2、M5、L2,髓外浸润多见,多预后不良。     

Trichosporon sepsis and leukemia.

Trichosporon cutaneum is a fungus known to cause superficial nodules over the distal third of hair shafts, mainly scalp hair, and to produce a clinical entity known as piedra. This superficial mycosis occurs mostly in temperate and tropical regions and is rarely seen in North America. Trichosporon cutaneum spesis is described here in a 12-year-old boy with acute lymphocytic leukemia in relapse. To our knowledge this is the first case reported in the literature. Emphasis is made of the increasing rate of fungal diseases as well as of "opportunistic" infections in this type of immunosuppressed patient.     

Juvenile chronic myeloid leukemia: therapeutic insights

Twelve children with juvenile chronic myeloid leukemia (JCML) received chemotherapy or bone marrow transplants. The median survival of the patients treated with myelosuppressive agents was 19 months. These results demonstrate that intensive chemotherapeutic and supportive measures can prolong survival in JCML but do not affect ultimate outcome. Purported differentiation inducers--low dose ara-C and 13-cis-retinoic acid--were not effective in two patients. Two patients were prepared for bone marrow transplantation with standard antileukemic cytoreduction regimens; one died very early post-transplant, and the other had early reemergence of his disease. The third transplant patient underwent transplantation after his disease had entered an accelerated phase. He received a different immunosuppressive pretransplant regimen, but the leukemia recurred. The latter two patients initially engrafted with mismatched T cell-depleted marrow grafts, but had recurrence of the disease. Our data suggest that marrow transplantation is possible for JCML patients without HLA-identical donors, but for successful marrow transplantation different measures are necessary to eradicate the abnormal stem cell compartment.     

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia

BACKGROUND: Patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma/leukemia have a poor prognosis and are frequently treated with low-intensity therapy. The authors investigated the feasibility and efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), a dose-intensive chemotherapy regimen, in patients with AIDS-associated Burkitt lymphoma/leukemia, as well as the possible impact of highly active antiretroviral therapy (HAART) in these patients. METHODS: Thirteen patients with AIDS-associated Burkitt lymphoma (six patients) or leukemia (acute lymphoblastic leukemia; seven patients) were treated with hyper-CVAD alternating with high-dose methotrexate and ara-C for a total of eight cycles. Nine patients received HAART from the start of induction chemotherapy (seven patients) or later in the course of chemotherapy (two patients). The median patient age was 43 years (range, 32-55). Nine patients were diagnosed with human immunodeficiency virus (HIV) infection at the time of diagnosis of Burkitt lymphoma/leukemia; the other 4 patients had been diagnosed with HIV infection for a median of 37 months (range, 18-137) prior to the diagnosis of Burkitt lymphoma/leukemia. The median absolute CD4 count from the 9 patients with evaluable counts was 77 cells/microL (range, 9-544); only one patient had a count > 200/microL. RESULTS: Twelve patients (92%) achieved a complete remission (CR) and one achieved a partial response (PR). Eight patients continued in CR after a median of 31 months (range, 7-45) at the time of writing. Five patients were alive and in CR over two years later. The median survival was 12 months, with 48% of patients alive after 2 years. Six of seven patients who received HAART from the start of chemotherapy were alive and in CR after a median of 29 months (range, 7-45). The four patients who did not receive HAART died. The regimen was universally myelosuppressive, but the toxicity profiles, recoveries from myelosuppression, and incidences of infectious complications were similar to that of non-HIV patients with Burkitt lymphoma/leukemia treated with the same regimen. CONCLUSIONS: Hyper-CVAD is an effective regimen for patients with AIDS-associated Burkitt lymphoma/leukemia, with acceptable toxicity. The combination of hyper-CVAD and HAART is associated with long-term survival in patients with the two diseases, which, until recently, were both considered invariably fatal and almost futile to treat medically.     

Clinical effect of granulocyte colony-stimulating factor on neutrophils and leukemic cells in myelogenous leukemia: analysis.

Clinical experiences with recombinant granulocyte colony-stimulating factor (rhG-CSF) in 13 acute (AML) and four chronic (CML) myelogenous leukemia patients are reported. Sixteen patients received rhG-CSF in support of treatment for life threatening infections and one CML patient in support of induction chemotherapy. After their first induction chemotherapy, six out of eight AML patients showed a rapid increase of neutrophils, recovered from infections and achieved complete remission (CR). One patient, in whom both neutrophils and blasts had increased during rhG-CSF administration, achieved CR through the next administration of chemotherapy (CR rate 87.5%). The last of the eight AML patients showed no increase of neutrophils, and died of interstitial pneumonitis. Two of five AML patients who received rhG-CSF after reinduction chemotherapy for relapsed or refractory leukemia achieved CR, a rate of 40%. In one of the two, the administration of rhG-CSF prior to induction chemotherapy seemed advantageous in achieving CR. During rhG-CSF administration, an increase of blastic cells in peripheral blood was observed in four out of all 13 AML patients. One of three CML patients, with a lymphoid crisis, showed an increase only of neutrophils, and recovered from infection. The other two showed increases of both neutrophils and blasts. One patient with CML in blastic crisis, undergoing induction chemotherapy with rhG-CSF administration, returned to the chronic phase. These clinical experiences suggest rhG-CSF to be effective in supporting infection therapy and in possibly enhancing the sensitivity of myelogenous leukemic blasts to antileukemic agents.     

Two cases of disseminated Trichosporon beigelii infection treated with combination antifungal therapy

Two patients with acute leukemia in whom disseminated Trichosporon beigelii infection developed are reported. The T. beigelii infection developed in the first patient while he was receiving 5-fluorocytosine. He was treated with amphotericin B in addition to 5-fluorocytosine. Despite the continued antifungal therapy, multiple organs were invaded by the organisms at autopsy. The second patient was treated with miconazole and norfloxacin. Although this combination antifungal therapy seemed to be effective, this patient required splenectomy for cure of the infection.     

A pilot study of carboplatin augmentation therapy for patients with poor risk acute non-lymphocytic leukemia.

Eleven patients with acute non-lymphocytic leukemia and persistent leukemia on a bone marrow done 6 days after the start of standard induction chemotherapy with daunorubicin and cytosine arabinoside were given augmentation chemotherapy with carboplatin as a continuous intravenous infusion over 3 days. Nine of the 11 patients (82%) entered complete remission. The hematologic and non-hematologic toxicities encountered by these patients were similar to those seen after conventional therapy alone with the exception of peripheral neuropathy in one patient. Of the two induction failures, one patient died of treatment-related toxicity and one patient had resistant leukemia.     

Early phase II trial of bestrabucil in hematological malignancies

Thirty-three patients with various hematological malignancies were treated with Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, at doses of 50-300 mg daily p.o., consecutively. Nineteen patients had previously received chemotherapy. Of 29 evaluable patients, there were one CR and three PRs among 6 patients with chronic lymphocytic leukemia, two CRs and one PR among 4 patients with malignant lymphoma, two PRs among 3 patients with adult T-cell leukemia, one PR among 4 patients with macroglobulinemia, one PR for one patient with essential thrombocythemia, and one PR for a patient with chronic myelocytic leukemia. Main side effects included G1 symptoms (14%), estradiol-related symptoms (24%) and myelosuppression (32%).     

成年人急性白血病治疗相关骨坏死十例分析

目的 分析与成年人急性白血病治疗相关的骨坏死的病因及影像学表现.方法 回顾2010年9月至2013年2月发生骨坏死的成年人急性白血病10例临床资料,所有患者均行磁共振成像（MRI）检查确诊.结果 10例患者中,4例为急性淋巴细胞白血病（ALL）,均行含大剂量激素的化疗,其中2例行造血干细胞移植（HSCT）,1例出现移植物抗宿主病（GVHD）并行激素治疗;6例为急性髓系白血病（AML）,所行化疗方案均不含激素,5例患者行HSCT,术后4例出现GVHD并行激素治疗;2例从未接受激素治疗,1例AML-M3患者曾接受4个疗程全反式维甲酸治疗.骨坏死确诊的时间距白血病确诊平均时间为25.1个月.病变多发9例,局部单发1例,受累部位包括股骨、胫骨、髌骨、髂骨、腰椎.X线片检查均为阴性表现;CT检查可见阳性表现,表现为不规则骨质密度减低区伴边缘环状骨质硬化;所有病灶均有典型MRI表现.结论 骨坏死是白血病治疗后影响患者生存质量的重要并发症,大剂量激素化疗、HSCT后GVHD的激素治疗、化疗药物的细胞毒性、AML-M3患者全反式维甲酸治疗等均可导致骨坏死的发生.MRI是发现骨坏死最有效的方法,X线片敏感性较差,CT可发现中晚期骨坏死病变,但其表现与非白血病患者骨坏死表现略有不同.     

Clinical and cytogenetic correlations of abnormal megakaryocytopoiesis in patients with acute leukemia and chronic myelogenous leukemia in blast crisis

It has been suggested that abnormalities of chromosome 3 at bands q21 and q26 are associated with the presence of increased numbers of abnormal megakaryocytes in patients with hematologic malignancies. The pretreatment bone marrows of 287 patients with leukemia (acute myeloid leukemia (AML), 225 patients; acute lymphocytic leukemia (ALL), 36 patients; or chronic myelogenous leukemia in blast crisis (CML-B), 26 patients) were reviewed to identify those with normal or increased numbers of megakaryocytes. Thirty-two patients with AML, one with ALL, and 10 with CML-B had normal or increased numbers of megakaryocytes. Of the 32 patients with AML, 19 patients had significant numbers of mononuclear or binuclear small megakaryocytes as well as megakaryocytes with separated nuclei ("micromegakaryocytes"). Cytogenetic analyses were obtained in 29 of 32 patients with AML and showed inv(3)(q21q26) (one patient); Ph1 (two patients); -5 and/or -7 (seven patients); normal karyotypes (10 patients). No patient with micromegakaryocytes had a chromosomal abnormality associated with a favorable prognosis. Overall, among 225 patients with AML, four had inv(3)(q21q26) or t(3;3)(q21;q26). Only one of these four patients had normal or increased numbers of megakaryocytes, although all four had micromegakaryocytes. One patient with CML-B had inv(3)(q21q26) but had decreased numbers of megakaryocytes and a platelet count of 24 x 10(3)/microliters. All five patients with abnormal chromosome 3 at bands q21 and q26 had additional cytogenetic abnormalities (Ph1 in two patients; -7 in three patients). Mean and median platelet counts were greater than 100,000/microliters for patients with marrow megakaryocytosis regardless of morphology, as well as for the patients with abnormalities involving 3q21 and 3q26. Abnormalities of megakaryocyte morphology, increases in the numbers of megakaryocytes, and normal to increased platelet counts are not uncommon in patients with acute leukemia and CML-B, and are not uniquely associated with changes involving chromosome 3.     

Re-induction of complete remissions in adults with acute non-lymphocytic leukemia

Thirty-five adults with acute non-lymphocytic leukemia in relapse following an initial remission were treated with intensive combination chemotherapy. Each patient received one of three re-induction programs which had already proven effective in the treatment of newly-diagnosed patients. Twenty (57%) of the patients undergoing re-induction therapy achieved complete remission. Clinical features which predicted a favorable response to therapy were female gender, rapid achievement of first remission, absence of infection, low plasma fibrinogen and serum LDH levels, and normal hepatic enzymes. Patients were more likely to respond if they also received at least one chemotherapeutic agent during re-induction to which they had not been previously exposed. The median duration of complete remission was 4.4 months (range 1–94+ months). Second remissions lasted over one year in four patients and two patients currently remain in complete remission at 49 and 94 months. Median survival for all patients who achieved remission was 10 months compared to only 2.5 months for those failing therapy. Since the re-induction of complete remission prolongs survival and can be accomplished in the majority of patients with leukemia in relapse, consideration should be given to using established intensive treatment programs prior to experimental chemotherapy in adults with advanced leukemia.     

A new combination of two intercalating agents (mitoxantrone + daunomycin) in adult refractory acute leukemia: the DON protocol

Summary A combination of two interacalating agents, mitoxantrone and daunorubicin with vincristine (the DON regimen) was studied in 16 patients with refractory acute leukemia, including three patients with myeloblastic transformation of refractory anemia with excess of myeloblasts after the failure of first-line chemotherapy and one additional patient with AML relapsing while off therapy. All patients had been heavily pretreated prior to receiving the DON regimen, and all but two had previously received high-dose anthracyclines. Of the 17 patients, nine (53%) who achieved complete remissions (CR) had myeloblastic leukemia. The three patients with acute lymphocytic leukemia did not achieve CR. Cardiac toxicity occurred in two patients and contributed to death in one. These results in very poor risk leukemia suggest a possible synergism in the action of the two intercalating agents and absence of increased cardiotoxicity.Presented in part at the 4th International Symposium on Therapy of Acute Leukaemias. Rome, February 7–12/1987     

Humanized anti‐CD19 chimeric antigen receptor‐T cell therapy is safe and effective in lymphoma and leukemia patients with chronic and resolved hepatitis B virus infection

Chimeric antigen receptor‐T (CAR‐T) cell therapy is a promising treatment for CD19⁺ B‐cell malignancies. However, elimination of B cells by anti‐CD19 CAR‐T cells may lead to the reactivation of hepatitis B virus (HBV) and related hepatitis in patients with HBV infection. This study aims to evaluate the safety and efficacy of humanized anti‐CD19 CAR‐T (hCAR‐T) therapy in B‐cell malignancies with HBV infection. Twenty relapsed/refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL) patients with HBV infection were treated with hCAR‐T therapy. Among them, five hepatitis B antigen‐positive patients who received antiviral prophylaxis did not develop HBV reactivation, including two patients who received both hCAR‐T and allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Among 15 patients with resolved HBV infection, two received antiviral prophylaxis, and the other 13 did not experience HBV reactivation without antiviral prophylaxis. One patient with resolved HBV infection experienced HBV reactivation 6 months after hCAR‐T therapy and sequential allo‐HSCT. Moreover, HBV infection did not affect in vivo expansion of hCAR‐T cells or increase the risk of severe cytokine release syndrome. In conclusion, hCAR‐T therapy is safe and effective in DLBCL and ALL patients with chronic and resolved HBV infection under proper antiviral prophylaxis.     

A new multidrug reinduction protocol with topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine for relapsed or refractory acute leukemia.

We report the results of a phase 2 nonrandomized single-arm trial of a combination therapy for relapsed or refractory leukemia. From January 1999 to June 2002, 28 patients with multiple relapsed or refractory acute leukemia received a combination of topotecan, vinorelbine, thiotepa, dexamethasone, and, for patients with an M3 marrow on day 7, gemcitabine. A total of 14 patients had pre-B-ALL (acute lymphoblastic leukemia), three had T-cell leukemia, nine acute myeloblastic leukemia (AML), and two biphenotypic leukemia. In all, 13 patients achieved a significant response (10 complete responses and three partial responses). Among the responders, five had pre-B-ALL, two had T-cell leukemias, five had AML, and one had biphenotypic leukemia. In total, 10 of these patients subsequently underwent hematopoietic stem cell transplantation, and four are alive without disease. One patient died, while in remission, of complications resulting from an episode of sepsis and pneumonia that occurred during topotecan, vinorelbine, thiotepa, dexamethasone, and gemcitabine (TVTG) reinduction. Other toxicities included grade 4 neutropenia in all patients and transient grade 2 hepatotoxicity in 10 patients (36%). In summary, we report that 47% of heavily pretreated pediatric patients with multiply relapsed or refractory leukemia achieved a significant response after therapy on the TVTG protocol. Further studies are warranted to evaluate the role of the TVTG combination in the treatment of leukemia.