INVASIVE ESOPHAGEAL ASPERGILLOSIS ASSOCIATED WITH ACUTE MYELOGENOUS LEUKEMIA: Successful Therapy with Combination Caspofungin and Liposomal Amphotericin B

Aspergillosis is one of the most common invasive fungal infections in patients with leukemia. In this patient group, this form of Aspergillus infection is a life-threatening condition with a mortality of 50–100%. The lungs are most often affected, but the esophagus can also be involved.The authors report the case of a child with leukemia who developed invasive esophageal aspergillosis. The condition was diagnosed by microscopic examination of endoscopic biopsy specimens. The patient was already receiving empirical liposomal amphotericin B when the diagnosis was made, so a second antifungal (caspofungin) was added to the regimen. This combination was successful. This case to demonstrates a case of successful treatment of invasive esophageal aspergillosis using combination therapy of liposomal amphotericin B and caspofungin.     

Kala-azar associated with coombs-positive autoimmune hemolytic anemia in the patients coming from the endemic area of this disease and successful treatment of these patients with liposomal amphotericin B

Kala-azar is an intracellular parasitic infection that infects and multiplies in the macrophages of the liver, the spleen, and the bone marrow. It is characterized by intermittent fever, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Although anemia is a usual finding, Coombs-positive autoimmune hemolytic anemia (AIHA) has rarely been reported with this disease. Pentavalent antimonial compounds remain the mainstay of treatment worldwide. Liposomal amphotericin B (L-AmB) is currently preferred in the treatment of kala-azar because of the resistance to pentavalent antimonals. The authors diagnosed kala-azar associated with Coombs-positive AIHA in 3 patients and treated them with L-AmB (1-5 mg/kg/day) for 30-36 days. Now, all of these patients are healthy following up at the outpatient base for 18-34 months. Kala-azar must be considered in patients with Coombs-positive AIHA and living in and coming from the endemic region for this disease, and it can be successfully treated with L-AmB.     

Combination therapy with caspofungin and liposomal amphotericin B for invasive aspergillosis

Ina 24-month-old girl with acute lymphoblastic leukemia and invasive aspergillosis, only combination therapy with liposomal amphotericin B and caspofungin achieved a good response. Combination therapy could be a useful treatment option in children with invasive fungal disease, but before it can be routinely recommended, carefully controlled in vivo studies and well-designed randomized clinical trials are needed.     

Pseudohypopyon: Extramedullary relapse of acute myelogenous leukemia with poor prognosis

An 11‐month‐old female presented to the emergency department with a 2‐week history of fever, increasing fussiness, emesis, and decreased urine output. She was diagnosed with acute myelogenous leukemia. Systemic chemotherapy with intensified intrathecal cytarabine was started, and the patient achieved a clinical remission after the first course of induction. Towards the end of her second course of induction she developed pseudohypopyon in each eye on consecutive days, heralding a central nervous system relapse. Pediatr Blood Cancer 2009;52:885–887. © 2008 Wiley‐Liss, Inc.     

T-cell acute lymphoblastic leukemia relapsing as acute myelogenous leukemia

We present the unusual case of a 16-year-old girl with T-cell acute lymphoblastic leukemia (ALL) with an early thymocyte immunophenotype without myeloid markers, who after 13 months of complete hematological remission relapsed as acute myelogenous leukemia (AML) with minimal differentiation and died of her disease. Whether the AML represented a relapse with lineage switch of the original immature T-cell clone or a new secondary malignancy, could not be proven due to the absence of molecular or clonal markers. This report suggests that a subset of CD7+ T-cell leukemias without mature T-cell antigens (CD4-, CD8-) are minimally differentiated and can relapse as AML.     

Amsa: A phase II trial in resistant and recurrent acute myelogenous leukemia

27 patients with resistant acute myelogenous leukemia (AML) were treated with AMSA. Three achieved a complete remission, and two a partial remission. Median survival for all patients was 12 weeks and was 16 weeks for responders.     

两性霉素B脂质体联合氟康唑治疗早产儿真菌性中枢感染研究

目的 探讨两性霉素B脂质体联合氟康唑治疗早产儿真菌感染的疗效及安全性.方法 收集2009.10 - 2011.5收治的中枢神经系统真菌感染早产儿7例,均应用两性霉素B脂质体联合氟康唑治疗,总疗程8 ～ 12周,监测治疗过程中患儿临床症状、体征及相关的血清学、脑脊液及影像学检查指标.结果 两性霉素B脂质体联合氟康唑足量长疗程治疗使早产儿真菌感染得到良好控制,除1例放弃治疗外,余6例症状明显改善,血培养均转阴,中枢神经系统病灶较前明显改善.治疗过程中未发现较严重的药物不良反应.结论 两性霉素B脂质体联合氟康唑治疗早产儿真菌性中枢感染有效且相对安全.     

Phase II study of gemcitabine in children with relapsed acute lymphoblastic leukemia or acute myelogenous leukemia (ADVL0022): a Children's Oncology Group Report

BACKGROUND: To determine the response rate and toxicity to gemcitabine administered as 10 mg/m2/min x 360 min weekly for 3 weeks in children with relapsed acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). Gemcitabine is a deoxycytidine analog that inhibits DNA synthesis and repair and has a broad spectrum of antitumor activity. PROCEDURE: From April 2001 to April 2003, 23 male and 9 female eligible patients were recruited for the Children's Oncology Group (COG) phase II study of Gemcitabine (ADVL0022). RESULTS: One of 20 evaluable patients with ALL and none of 10 evaluable patients with AML had complete responses to gemcitabine; there were no partial responses. Grade 3 or 4 hematologic toxicity and liver toxicity were common during therapy. Only one patient was alive 1 year after entry. The estimated 1-year overall survival probability for the 32 patients was 4% (SE = 3%). CONCLUSIONS: Gemcitabine at the dose and schedule in this trial was not effective for children with relapsed AML or ALL.     

Remission induction in acute myelogenous leukemia using cytosine arabinoside synchronization: A southwest oncology group study

The use of cytosine arabinoside (Ara-C) infused at kinetically suggested intervals is reported in 40 pediatric patients with acute myelogenous leukemia (AML) and its subtypes. Response was observed in 17 of the 34 evaluable patients. However, the severe, often fatal effects of the regimen prevent its recommendation as a standard induction regimen in AML in children.     

The prognostic value of serum lysozyme activity in acute myelogenous leukemia

Serum lysozyme activity was measured in samples from adult patients with acute leukemia, malignant tumors, and in normal adults. Twenty-eight adult patients with acute myelogenous leukemia (AML) had significantly elevated levels of lysozyme at diagnosis, and none of the adults fell within the normal range. Thirty-two patients with AML in complete remission had lysozyme levels comparable to normal adults, whereas patients with AML in relapse (eight cases) also had abnormally high levels of lysozyme activity. Ten patients with AML in remission and off therapy also had normal lysozyme levels. Three patients with acute lymphatic leukemia had normal lysozyme levels, while one child with monomyelocytic leukemia had substantially elevated lysozyme levels before treatment. It seems that in patients in remission and with normal blood values, the serum lysozyme activity is valuable for monitoring the remission.     

Assessment of nephrotoxicity of high-cumulative dose of liposomal amphotericin B in a pediatric patient who underwent allogeneic bone marrow transplantation

We describe a 9-yr-old boy who received the highest cumulative dose so far reported of liposomal amphotericin B.The patient underwent an allogeneic bone marrow transplantation (BMT) for adrenoleucodystrophy, after a conditioning regimen with busulfan, thiothepa and cyclophosphamide. Rabbit antithymoglobulin, cyclosporin and prednisone were used as prophylaxis against graft vs. host disease (GVHD). Post-transplant Epstein-Bar-virus-related lymphoma was diagnosed on day +68 and was treated with donor-derived lymphocytes. The patient developed a severe form of GVHD, and a progressive worsening of his neurological status because of progression of his underlying disease. Death from septic shock occurred 23 months after BMT. During prolonged hospitalization, 19,750 mg of liposomal amphotericin B, about 1000 mg/kg, were given for prophylactic or empirical therapeutic purposes without significant nephrotoxicity. This case suggests that liposomal amphotericin B is safe and well-tolerated even if is administered for long periods and a cumulative dose fivefold greater than the nephrotoxic threshold of amphotericin B deoxycholate is achieved.     

Caspofungin for invasive fungal infections: combination treatment with liposomal amphotericin B in children undergoing hemopoietic stem cell transplantation

Abstract:  Invasive fungal infections often prove difficult to eradicate especially in the stem cell transplant setting. Amphotericin has been the mainstay of treatment for years but has significant toxicity. Newer antifungal agents, such as caspofungin, have shown promising results in adults, particularly when used in combination with amphotericin as both drugs differ in their mode of action. However, there are few data from children and no previous published information about the use of Caspofungin after paediatric stem cell transplantation. We report our experience in children with proven invasive fungal infections after stem cell transplantation. This combination was non-toxic, and two of three patients survived their infections.     

Successful antifungal combination therapy with voriconazole and caspofungin

A 12-year-old boy in third remission of an acute lymphoblastic leukaemia developed infection of lung and paranasal sinuses with Aspergillus flavus in neutropenia. Because of the high risk of leukaemia-relapse bone marrow transplantation (BMT) from a matched unrelated donor was carried out despite invasive pulmonary aspergillosis (IPA). It is the first reported patient with IPA, who was successfully treated by the antifungal combination therapy with voriconazole and caspofungin therapy during myeloablative BMT. Despite 6 weeks of aplasia, a dramatic decrease of lesions highly suggestive of aspergillosis was observed after BMT. Since discharge-oral voriconazole monotherapy has been continued.     

Hemophagocytic lymphohistiocytosis associated with precursor B acute lymphoblastic leukemia

We report a case of a child with precursor-B acute lymphoblastic leukemia (ALL) who experienced refractory thrombocytopenia and massive splenomegaly during standard induction chemotherapy. He was diagnosed with hemophatocytic lymphohistiocytosis (HLH) during induction. Clinical and laboratory evaluation showed no evidence of infectious cause to HLH. Pancytopenia and HLH persisted after consolidation therapy even with remission from leukemia. After failure to control HLH with ALL-directed therapy and HLH-directed therapy, the patient underwent unrelated donor hematopoietic stem cell transplantation 8 months after diagnosis. He is 34 months post-transplant and in remission from leukemia and HLH.