Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy. We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma. The patient was admitted with bulky abdominal masses of B cell lineage non-Hodgkin's lymphoma. After 2 cycles of systemic chemotherapy of the Vanderbilt regimen, the patient underwent ASCT with high dose chemotherapy of the BEAC regimen. She also received radiation of 48 Gy for the residual periportal lymphadenopathy. The initial cytogenetic analysis of the infused mononuclear cells revealed a normal karyotype. Twenty two months after the ASCT, pancytopenia was noted and her bone marrow aspirate showed dysplastic hemopoiesis with myeloblasts up to 12% of nonerythroid nucleated cells. The patient was diagnosed as t-MDS (refractory anemia with an excess of blasts). Cytogenetic analysis showed complex chromosomal abnormalities including 11q23 rearrangement, which is frequently found in topoisomerase II inhibitor-related hematologic malignancies. Four months later, it was noted that the t-MDS had evolved into an overt t-AML. Cytogenetic analysis showed an evolving pattern with more complex abnormalities. The patient was treated with combination che-motherapy, but her leukemic cells were resistant to the therapy.
Adult ; Antineoplastic Agents, Phytogenic/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/*adverse effects ; B-Lymphocytes/cytology ; Bone Marrow Cells/pathology ; Carmustine/*adverse effects ; Chromosome Aberrations ; Chromosomes, Human, Pair 11 ; Combined Modality Therapy/adverse effects ; Cyclophosphamide/*adverse effects ; Cytarabine/*adverse effects ; Etoposide/*adverse effects ; Female ; Gene Rearrangement ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Leukemia, Myeloid, Acute/*etiology/genetics ; Lymphoma, Non-Hodgkin/*therapy ; Myelodysplastic Syndromes/*etiology/genetics ; Neoplasms, Second Primary/*etiology ; Pelvis ; Pregnancy ; Pregnancy Complications, Neoplastic/*therapy ; Transplantation, Autologous

BACKGROUND: High-dose chemotherapy is increasingly employed in many refractory malignant diseases. This therapy has been reported to increase response rate and survival benefits but it is also associated with higher treatment-related morbidity and mortality. We evaluated clinical characteristics and course of the pulmonary toxicity following high-dose chemotherapy with peripheral blood stem cell transplantation. METHODS: Ninety-seven patients who had received high-dose chemotherapy with peripheral blood stem cell transplantation were evaluated. Five patients who developed lung lesions which were not related to infection nor primary malignant disease underwent transbronchial lung biopsy. The patients' clinical characteristics, treatments, and prognosis were reviewed retrospectively. RESULTS: Five patients(5.1%) developed idiopathic pneumonia syndrome. The high dose chemotherapy regimens employed were cyclophosphamide, BCNU, and cisplatin in 3 cases, one case of BCNU, etoposide, Ara-C, cyclophosphamide combination, and a regimen consisting of BCNU, etoposide, Ara-C, and melphalan. The total dose of BCNU used was 300-400 mg/m2 and that of cyclophosphsmide was 6,000 mg/m2. All of 5 patients received radiation therapy before this treatment. After an average duration of 14 weeks (4-26 weeks) of high-dose chemotherapy, patients developed cough, dyspnea and fever. The chest X-rays showed bilateral diffuse infiltration in 3 cases and the focal infiltration in the other 2 cases. All the patients received corticosteroid therapy as a treatment for the lung lesions. Two of them progressed to acute respiratory distress syndrome and died. Three patients recovered without residual lung lesion but one of them died of dilated cardiomyopathy. CONCLUSION: High-dose chemotherapy with peripheral blood stem cell transplantation especially which containing BCNU regimen may develop idiopathic pneumonia syndrome related to pulmonary toxicity and corticosteroid therapy may be beneficial in some cases.
Biopsy ; Cardiomyopathy, Dilated ; Carmustine ; Cisplatin ; Cough ; Cyclophosphamide ; Cytarabine ; Drug Therapy* ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Etoposide ; Fever ; Humans ; Lung ; Melphalan ; Mortality ; Peripheral Blood Stem Cell Transplantation* ; Pneumonia ; Prognosis ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Thorax

OBJECTIVETo explore high effective and low toxic chemotherapeutic regimens in the treatment of non-small-cell lung cancer (NSCLC).

METHODSA total of 126 patients with advanced NSCLC (Stage III, IV) were randomly divided into two groups: high dose impulsion chemotherapy group (HDIC group) and low dose density chemotherapy group (LDDC group) with 54 patients in HDIC group who received paclitaxel 135-175 mg/m2 on day 1, DDP 80-100 mg/m2 on day 1 and BCNU 125 mg given for brain metastasis on days 1-3 in a 4-6 weeks cycle. Seventy-two patients in LDDC group were given paclitaxel 60-80 mg/m2 on day 1, DDP 40-80 mg/m2 on day 1 repeated weekly and BCNU 125 mg given for brain metastasis with an interval of 2 weeks, in a 4-6 weeks cycle. Antiemetic agent and fluid were administered routinely in HDIC group whereas LDDC group was given antiemetic agent only.

RESULTSOf 157 courses in HDIC group, an average of 2.9 courses per patient, CR 3, PR 23, SD 17 and PD 11 were observed. The effective remission rate was 48.1%, the median effective remission period was 4.5 months and the 1-year survival rate was 46.3%. Of 184 courses in LDDC group, an average of 2.6 courses per patient, CR 9, PR 30, SD 24 and PD 9 were observed. The effective remission rate was 54.2%, the median effective remission period was 6 months and the 1-year survival rate was 56.9%. The effective remission rate and the 1-year survival rate were higher in HDIC group than those in LDDC group, but there was no statistical difference between the two groups (P > 0.05). Severe toxicity was higher in HDIC group than in LDDC group. Two patients in HDIC group died of treatment-related complications (3.7%). Quality of life was better in LDDC group (70.8%) than in HDIC group (51.9%).

CONCLUSIONWhen comparing with high dose impulsion, low dose density regimen of paclitaxel plus cisplatin is more effective and better tolerated with improvement of quality of patients' life in the treatment of NSCLC due to its low dose and short interval duration.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Brain Neoplasms ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; secondary ; Carmustine ; administration & dosage ; Cisplatin ; administration & dosage ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; Quality of Life ; Remission Induction ; Survival Rate ; Thrombocytopenia ; chemically induced