melphalan and Leukemia--Myelomonocytic--Acute

The incidence of secondary myelodysplasia/acute myeloid leukemia (AML) was retrospectively assessed in an international joint study in 305 node-positive breast cancer patients, who received mitoxantrone-based high-dose chemotherapy (HDCT) followed by autologous stem cell support as adjuvant therapy. The median age of the patients was 57 years (range 22-67). In all, 268 patients received peripheral blood stem cells, and 47 patients received autologous bone marrow. After a median follow-up of 57 months (range 10-125), three cases of secondary AML (sAML) were observed, resulting in a cumulative incidence of 0.94%. One case of sAML developed 18 months after HDCT (FAB M3) The karyotype was translocation 15;17 and, after induction therapy, the patient underwent autologous stem cell transplantation, and is in complete remission (CR) of both breast cancer and AML. The second patient developed AML (FAB M4eo with inversion 16) 5 months after HDCT. This patient achieved CR after induction therapy, but died of infectious complication. A third patient developed AML (FAB M4) 6 months after HDCT. She achieved CR after induction therapy, but relapsed and expired 28 months after diagnosis of AML. sAML after mitoxantrone-based HDCT is a possible, but rare complication in breast cancer patients.

Topics: Acute Disease; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Epirubicin; Female; Humans; Incidence; Leukemia, Myeloid; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Leukemia, Radiation-Induced; Lymphatic Metastasis; Melphalan; Middle Aged; Mitoxantrone; Neoplasms, Second Primary; Paclitaxel; Peripheral Blood Stem Cell Transplantation; Radiotherapy, Adjuvant; Thiotepa; Transplantation Conditioning; Transplantation, Autologous

In vitro and clinical studies have shown antineoplastic effects of hyperthermia alone and in combination with other treatment modalities. Synergistic cytotoxic effects of chemotherapy and hyperthermia have been demonstrated on leukemic cell clones in vitro. It seems that hyperthermia is effective in overcoming chemotherapy resistance. Several groups treated solid tumors by using total body hyperthermia (TBHT). However, only a few studies have been reported investigating the clinical effects of TBHT in myeloproliferative disorders. We report the case of a 7-year-old boy with myelomonocytic leukemia treated with TBHT (2 hours, 42 degrees C) combined with etoposide (600 mg/m2), melphalan (30 mg/m2) and hyperglycemia (200-300 mg/dl). Within 24 hours after TBHT, the leukemic cells decreased after TBHT from 53,000/microliters to zero. Skin leukemic infiltrates, resistant to conventional treatment, also responded well. Although our patient relapsed 34 days after TBHT, these results indicate that TBHT in combination with cytotoxic treatment may be a useful treatment modality in refractory leukemia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Etoposide; Glucose; Humans; Hyperthermia, Induced; Leukemia, Myelomonocytic, Acute; Male; Melphalan; Time Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Drug Evaluation; Etoposide; Hodgkin Disease; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Lomustine; Melphalan; Mitoxantrone

To evaluate the safety and efficacy of a preparative regimen consisting of fractionated total-body radiation (9.9 to 12 Gy) and melphalan (140 mg/m(2) in a single dose) in children with acute myeloid leukemia in first complete remission (CR) given autologous bone marrow transplantation (ABMT).. Fifty-three children (30 males and 23 females; age range, 1.5 to 18 years) were enrolled onto the study. The median time from first CR to ABMT was 3.5 months (range, 1.4 to 13 months), with 45 patients (85%) undergoing transplantation within 6 months from the diagnosis. Forty-five patients received in vitro marrow purging with standard-dose mafosfamide (100 microg/mL), seven patients were treated with interleukin-2 before marrow collection, and in the remaining child, the marrow was unmanipulated. The median infused cell dose was 1.8 x 10(8)/kg (range, 0.4 to 5.8 x 10(8)/kg).. All patients but one achieved hematopoietic engraftment, with a median time to neutrophil recovery of 24 days (range,11 to 66 days). Treatment-related toxicity was moderate and consisted mainly of mucositis. One patient died from cytomegalovirus interstitial pneumonia, and one died from pulmonary hemorrhage. Fourteen patients (26%) relapsed at a median time of 6 months after ABMT (range, 2 to 17 months), with a cumulative relapse probability of 29% (95% confidence interval, 16% to 42%). The 5-year Kaplan-Meier estimate of survival for all 53 patients was 78% (range, 65% to 90%), whereas the overall 5-year disease-free survival was 68% (range, 55% to 81%), with a median follow-up duration of 40 months (range, 7 to 130 months).. These data suggest that, in our cohort of patients, the combination of total-body irradiation and melphalan is safe and associated with good antileukemia activity, making ABMT an appealing alternative for postremission therapy in children with acute myeloid leukemia in first CR.

Topics: Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Infant; Leukemia, Myelomonocytic, Acute; Male; Melphalan; Outcome Assessment, Health Care; Prospective Studies; Remission Induction; Transplantation Conditioning; Transplantation, Autologous; Transplants; Whole-Body Irradiation

Risk factors associated with the development of aGVHD in the gastrointestinal tract have not been studied in depth. We retrospectively assessed 25 pediatric patients with MDS and JMML and compared the treatment outcome of two different conditioning regimens. Seventeen children (68%) underwent conditioning with busulfan (Bu), cyclophosphamide (Cy), and melphalan (Mel) and eight children (32%) with Bu and Cy. Gastrointestinal aGVHD stages II-IV (day 0-100) were observed in 47% (eight of 17) of the patients in the BuCyMel group and in none (0 of 8) in the BuCy group (p < 0.05). In patients who developed gastrointestinal aGVHD stages III-IV, a 24-h variation in the Bu concentration with a nighttime peak was noted. HC and liver aGVHD stages II-IV were observed in 47% (eight of 17) and 35% (six of 17) after BuCyMel conditioning and in 0% (0 of 17) and 12.5% (one of eight) after BuCy conditioning. The overall survival rate was 53% (nine of 17) in the BuCyMel group and 62.5% (five of eight) in the BuCy group. In conclusion, the addition of melphalan to the BuCy conditioning regimen resulted in severe gastrointestinal complications and did not improve overall survival.

Topics: Adolescent; Busulfan; Child; Child, Preschool; Cyclophosphamide; Female; Gastrointestinal Tract; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Infant; Leukemia, Myelomonocytic, Acute; Male; Melphalan; Myelodysplastic Syndromes; Retrospective Studies; Risk Factors; Transplantation Conditioning; Treatment Outcome

Graft rejection is a serious complication in cord blood transplantation (CBT), but little is known about the mechanism of rejection. To investigate the potential role of T lymphocytes in graft rejection, we isolated a CD8(+) cytotoxic T lymphocyte (CTL) clone of recipient origin from blood obtained from a patient with graft rejection after CBT from an HLA-mismatched unrelated donor. The isolated CTL clone specifically recognized an HLA-B( *)1501 molecule as an alloantigen, which was expressed in donor cells but not in recipient cells. The results of a microchimerism analysis specific for HLA-B( *)1501 and a polymerase chain reaction assay specific for the T cell receptor on DNA from pretransplant peripheral blood mononuclear cells revealed that the patient was exposed to HLA-B( *)1501 prior to CBT, and that the CTL clone was in the patient's blood prior to transplantation. The present study demonstrates a potential role for pretransplant CTL in graft rejection following CBT.

Topics: Clone Cells; Cord Blood Stem Cell Transplantation; Electroporation; Female; Graft Rejection; Histocompatibility Testing; HLA Antigens; HLA-A Antigens; HLA-B Antigens; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Leukemia, Myelomonocytic, Acute; Male; Melphalan; Middle Aged; Polymerase Chain Reaction; Receptors, Antigen, T-Cell; T-Lymphocytes, Cytotoxic; Transfection; Transplantation Chimera; Vidarabine

A 10-year-old girl diagnosed with acute myeloid leukemia FAB M4 failed to achieve remission following several courses of induction chemotherapy. From the first course of chemotherapy the patient had continuous marrow aplasia, managed by a total of 57 granulocyte transfusions. After reinduction and reduced-intensity conditioning including fludarabine, Campath-1H, and melphalan, the patient received unmanipulated marrow from an HLA-matched unrelated donor. Leukocyte and platelet engraftment was observed on day +18 and +50, respectively. Graft-versus-host disease did not occur. The patient is alive and well in complete remission 18 months after transplantation with complete donor chimerism.

Topics: Alemtuzumab; Anemia, Aplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Female; Graft vs Host Disease; Granulocytes; Humans; Leukemia, Myelomonocytic, Acute; Melphalan; Neoplasm Recurrence, Local; Remission Induction; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

The authors describe a young boy with juvenile myelomonocytic leukemia (JMML) who relapsed 45 days after HLA and killer immunoglobulin-like receptor (KIR) mismatched unrelated donor bone marrow transplant (MMUD-BMT) and subsequently developed life-threatening graft-versus-host disease (GvHD). Treatment with 6-mercaptopurine (6-MP) appeared to control severe GvHD and possibly prevented recurrence of leukemic relapse.

Topics: Antimetabolites, Antineoplastic; Busulfan; Cyclophosphamide; Graft vs Host Disease; Graft vs Leukemia Effect; Hematopoietic Stem Cell Transplantation; Histocompatibility; HLA-B Antigens; HLA-B52 Antigen; HLA-C Antigens; Humans; Infant; Leukemia, Myelomonocytic, Acute; Male; Melphalan; Mercaptopurine; Receptors, Immunologic; Receptors, KIR; Remission Induction; Secondary Prevention; Transplantation Conditioning; Transplantation, Homologous

Currently no treatment has proved successful in inducing ovarian steroidogenic and/or gametogenic recovery in patients with haematological malignancies treated by cytotoxic chemotherapy once biochemical failure becomes manifest i.e., when FSH levels exceed 40 IU/L. This paper reports two such cases with classical biochemical ovarian failure in which ovarian function was induced by brief stimulation with Human Menopausal Gonadotrophin (HMG).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Carmustine; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Female; Follicle Stimulating Hormone; Hodgkin Disease; Humans; Leukemia, Myelomonocytic, Acute; Luteinizing Hormone; Melphalan; Menotropins; Ovulation Induction; Podophyllotoxin; Prednisone; Pregnancy; Pregnancy, Multiple; Primary Ovarian Insufficiency; Remission Induction; Teniposide; Thioguanine; Vincristine

We describe a patient with multiple myeloma who developed secondary acute myelomonocytic leukemia after long-term melphalan treatment. Following two courses of low-dose cytarabine, complete remission of the A.M.L. was achieved. Shortly thereafter an aggressive relapse of the quiescent myeloma occurred with acute renal failure and massive infiltration of bone marrow with multinucleated giant plasma cells. Although it is well known that administration of melphalan to patients with multiple myeloma increases the likelihood of A.M.L., this case demonstrates that treatment of A.M.L. in a patient with multiple myeloma may perhaps influence the course of multiple myeloma.

Topics: Antigens, CD; Bone Marrow; Cytarabine; Female; HLA-DR Antigens; Humans; Leukemia, Myelomonocytic, Acute; Melphalan; Middle Aged; Multiple Myeloma; Neoplasms, Second Primary; Recurrence

A 32-year-old woman was admitted to our hospital with pyrexia and general lymphadenopathy in July 1984. She was diagnosed as having malignant lymphoma (follicular, small cleaved cell), stage IV based on the histological findings of lymph nodes in the neck and bone marrow specimen. She was treated with melphalan orally for 3 years, followed by MACOP-B. She attained partial remission with MACOP-B. Thereafter, she received melphalan or Endoxan orally as maintenance therapy. She developed fever and swelling in the gingivae in October 1989. Peripheral blood showed WBC 80,200/microliters with 7.5% myeloblasts and 85.5% monocytes. Bone marrow aspirate revealed hypercellularity with 47.9% myeloblasts, 46.5% monoblasts and monocytes, which were positive for peroxidase and NSE stains. The karyotype of bone marrow cells showed a 46,XX,t(9;11). The lysozyme in serum was elevated. She was diagnosed having AML (M4). DCMP regimen was initiated but failed to achieve CR. Consequently she received MEC regimen and obtained complete remission, lasting for 6 months. Patients with second leukemia have a low probability of achieving complete remission using conventional chemotherapy. The MEC regimen is thought to be one of the most promising treatments for secondary leukemia.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Humans; Leukemia, Myelomonocytic, Acute; Lymphoma, Follicular; Melphalan; Methotrexate; Neoplasms, Second Primary; Prednisolone; Remission Induction; Vinblastine; Vincristine

Alkalating chemotherapeutic agents are frequently implicated in the development of acute non-lymphocytic leukemia. A case report illustrates the danger of administering a prolonged course of adjuvant chemotherapy with Melphalan following mastectomy for breast cancer.

Topics: Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Chromosome Deletion; Chromosomes, Human, Pair 7; Female; Humans; Leukemia, Myelomonocytic, Acute; Melphalan; Middle Aged; Risk Factors; Time Factors