mercaptopurine and Leukemic-Infiltration

A 65-year old female was diagnosed to have acute nonlymphocytic leukemia (M2) in July, 1990. Complete remission was achieved by BHAC-DMP (enocitabine, daunorubicin, 6-mercaptopurine, prednisolone) therapy. Complete remission had continued without symptoms for about two years. Uterial infiltration of leukemic cells occurred in May, 1992, followed by bone marrow relapse after two months. The second hematological complete remission was obtained after one course of the chemotherapy, but uterial infiltration of leukemic cells had still remained.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Myeloid, Acute; Leukemic Infiltration; Mercaptopurine; Prednisolone; Recurrence; Remission Induction; Uterus; Vincristine

The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis.. With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype.. The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome.. TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Central Nervous System Diseases; Cyclophosphamide; Cytarabine; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Injections, Spinal; Leukemic Infiltration; Mercaptopurine; Methotrexate; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Risk Factors; Vincristine

Lymphoblastic lymphoma (LBL) is a rare form of non-Hodgkin's lymphoma (NHL). Cutaneous LBL is seen in less than 20% of patients.. Herein, we report the case of a 66-year-old male patient without any previous disease history of note and who was presenting a gradually spreading tumoral lesion of the scalp, several purplish macules and nodules on the trunk, and a single spinal adenopathy. A thoracic-abdominal-pelvic CT scan performed for acute renal failure, revealed extensive infiltration of retroperitoneal tissue. Skin biopsies and staging tests indicated LBL-T with associated cutaneous, bone and lymph node retroperitoneal lesions with no mediastinal mass. After two months of treatment with CHOP (four courses), the cutaneous lesions and abdominal tumoral mass had regressed and renal function had returned to normal.. There have been 13 reported cases of LBL with cutaneous involvement; most of these patients were young (under 30 years) and presented multiple cutaneous lesions (nodules or tumors) associated with numerous peripheral adenopathies, invasion of the bone marrow, and in many cases, a mediastinal mass. The clinical presentation of LBL-T in our case is novel on account of the cutaneous sites, associated with abdominal tumoral syndrome, without mediastinal infiltration, and with a single peripheral adenopathy, in an elderly subject.

Topics: Acute Kidney Injury; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone and Bones; Cyclophosphamide; Doxorubicin; Humans; Immunophenotyping; Leukemic Infiltration; Lymph Nodes; Male; Mercaptopurine; Methotrexate; Organ Specificity; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Retroperitoneal Space; Skin; Vincristine

Topics: Adult; Aminoglycosides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Benzoates; Bone Marrow; Bone Neoplasms; Combined Modality Therapy; Doxorubicin; Drug Resistance, Neoplasm; Gemtuzumab; Hematopoietic Stem Cell Transplantation; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Oxides; Radionuclide Imaging; Remission Induction; Salvage Therapy; Sarcoma, Myeloid; Soft Tissue Neoplasms; Tetrahydronaphthalenes; Tretinoin

Central nervous system (CNS) involvement is rarely observed in acute promyelocytic leukemia (APML). Most cases of CNS involvement occur at relapse rather than at presentation. Because of the extremely low incidence of CNS disease, diagnostic lumbar puncture is not routinely required and prophylactic intrathecal chemotherapy is not routinely administered. Here, we describe a teenage patient with newly diagnosed APML, chloromas, and symptomatic CNS involvement confirmed by MRI and cerebrospinal fluid (CSF) findings.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Combined Modality Therapy; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Mercaptopurine; Methotrexate; Oncogene Proteins, Fusion; Radiotherapy; Sarcoma, Myeloid; Tretinoin

Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Central Nervous System; Central Nervous System Diseases; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Electroencephalography; Female; Humans; Infant; Leukemic Infiltration; Magnetic Resonance Imaging; Male; Mercaptopurine; Methotrexate; Peripheral Nervous System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Retrospective Studies; Tomography, X-Ray Computed; Vincristine

Topics: Adrenal Cortex Hormones; Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleosides; Asparaginase; Bone Marrow Diseases; Diagnosis, Differential; Doxorubicin; Humans; Ischemia; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Myelitis, Transverse; Paraplegia; Paresthesia; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Salvage Therapy; Spinal Cord; Vincristine

To evaluate the treatment results of central nervous system preventive therapy (CNSP) with triple intrathecal therapy (TIT) alone in children with acute lymphoblastic leukemia (ALL).. We retrospectively studied a cohort of 59 patients with median follow-up time 50.6 months (range: 27-80 months) at a single institution in Taiwan. Patients with ALL were classified in risk groups at diagnosis. TPOG-ALL-93 protocols and TPOG-ALL-2002 protocols were used. Both protocols were for multicenter studies in Taiwan and contained protocols for standard-risk (SR), high-risk (HR), and very-high-risk (VHR) patients. In this study, we used TIT alone for CNSP. In all ALL patients, methotrexate, hydrocortisone, and cytarabine were given at age-dependent doses.. As of October 2006, patients had a 3-year event-free survival and an overall survival 89.4 +/- 4.1% (S.E.) and 93.1 +/- 3.3%, respectively. Under TIT no patients had complications such as seizure, encephalitis, or infection, and no morbidities like those caused by cranial irradiation. In this study, we used TIT alone for CNSP and had no CNS relapse.. In the context of effective systemic therapy, TIT alone appears to be effective CNSP for most patients with ALL.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Central Nervous System; Child; Child, Preschool; Cranial Irradiation; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Epirubicin; Female; Follow-Up Studies; Humans; Hydrocortisone; Infant; Injections, Spinal; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Retrospective Studies; Risk; Survival Analysis; Vincristine

A 71-year-old man was admitted to our hospital because of right lower abdominal pain. He was suspected of having acute appendicitis and soon after admission, appendectomy was performed. Macroscopically, the appendix was greatly swollen and reddened, but had no abscess. Microscopically, polymorphonuclear leukocytes were not found, but diffuse infiltration of atypical cells was observed. Examination of a bone marrow aspirate revealed 74% blasts that were peroxidase stain positive. We diagnosed acute myelogenous leukemia (FAB classification, M2). He received induction chemotherapy, but died 49 days after admission. Leukemic cell infiltration of the appendix is rare and acute appendicitis as the initial manifestation of leukemia is even rarer.

Topics: Aged; Antigens, CD; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Appendectomy; Appendicitis; Appendix; Combined Modality Therapy; Cytarabine; Daunorubicin; Disease Progression; Fatal Outcome; Humans; Idarubicin; Immunophenotyping; Leukemia, Myeloid, Acute; Leukemic Infiltration; Male; Mercaptopurine; Sarcoma, Myeloid

We describe a 69-year-old Japanese male with acute leukemia with a CD7+ and CD56+ immunophenotype presenting with multiple lymphadenopathy. He was treated with idarubicin and cytosine arabinoside. Although the leukemia showed partial response, the patient did not achieve complete remission. He died of sepsis due to severe neutropenia after the third course of chemotherapy. His autopsy revealed blast infiltration in the lymph nodes, liver, spleen and vertebral bone marrow. Recently, CD7+ and CD56+ myeloid/natural killer precursor acute leukemia has been associated with a poor prognosis. Our case illustrates that myeloid/natural killer cell precursor acute leukemia shows some response to intensive chemotherapy for acute myeloid leukemia, but such therapy is insufficient to effect a cure. To overcome the resistance of this disease to chemotherapy, further studies should explore other treatment strategies.

Topics: Acute Disease; Aged; Antigens, CD; Antigens, CD7; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; CD56 Antigen; Cytarabine; Daunorubicin; Diagnosis, Differential; Etoposide; Fatal Outcome; Humans; Idarubicin; Killer Cells, Natural; Leukemia, Myeloid; Leukemic Infiltration; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Mitoxantrone; Myeloid Cells; Neoplastic Stem Cells; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sarcoma, Myeloid; Sialic Acid Binding Ig-like Lectin 3

We examined the pre-treatment bone marrow samples from 200 consecutive adult patients with acute lymphoblastic leukemia (ALL) treated on various protocols at the University of Texas, M.D. Anderson Cancer Center between 1986 and 1998. Standard MFC techniques were used to determine CD56 expression on the leukemia blasts cells. The expression of CD56 was correlated with clinical characteristics at diagnosis, response to therapy, survival and disease-free survival. Blast expression of CD56 (> or = 20% of leukemic blasts) was seen in 16 (8%) of patients, with a median expression of 67% (range 20-99%). CD56 expression was associated with a higher incidence of central nervous system (CNS) disease at diagnosis (19% versus 4%; P=0.016). Incidence of CNS disease at any time was higher in patients with CD56+ disease (31% versus 14%; P=0.057). Among the 109 patients uniformly treated with the hyperCVAD regimen, CD56 expression was associated with a statistically significant higher incidence of CNS disease (33% versus 9%; P=0.026). CD56 expression in ALL is uncommon but may predict a higher risk for CNS disease. If these results are confirmed, CD56 expression could be used in combination with other high-risk features (e.g. lactate dehydrogenase (LDH), S-phase fraction, mature B-cell phenotype) to design a risk-oriented approach to CNS prophylaxis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Marrow Cells; CD56 Antigen; Cell Adhesion; Central Nervous System; Chemotaxis, Leukocyte; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Gene Expression; Humans; Incidence; Leukemic Infiltration; Life Tables; Male; Mercaptopurine; Methotrexate; Middle Aged; Neoplasm Proteins; Neoplastic Stem Cells; Neurons; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Prednisone; Risk; Survival Analysis; Treatment Outcome; Vincristine

During T cell selection in the thymic cortex more than 90% of the thymocytes are eliminated by apoptosis. Based on this biology, we propose to define blasts of T cell acute lymphoblastic leukemia (ALL) with the phenotype of cortical thymocytes (CD1+ and/or CD4+ 8+) as selection-related (SR) and all other T-ALL immunophenotypes as non-selection-related (NSR). The COALL cooperative treatment studies for childhood ALL offer a tool to study the outcome in T-ALL subgroups as children with T-ALL are allocated uniformly to the high risk arm of the protocol. In the COALL-85, -89 and -92 protocols, 39/83 cases presented as SR and 44/83 cases as NSR. Five-year event-free survival of SR phenotype is significantly better compared to the NSR group (0.87 +/- 0.06 vs 0.66 +/- 0.07, log rank test, P = 0.01). T-ALL with SR phenotype is a distinct subgroup of leukemia with excellent prognosis under a high risk treatment protocol.

Topics: Adolescent; Antigens, CD; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Central Nervous System; Child; Child, Preschool; Clonal Deletion; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Follow-Up Studies; Germany; Humans; Immunophenotyping; Infant; Leukemia-Lymphoma, Adult T-Cell; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Multicenter Studies as Topic; Neoplastic Stem Cells; Prednisolone; Remission Induction; Risk; T-Lymphocyte Subsets; Teniposide; Thioguanine; Treatment Outcome; Vincristine

Infants diagnosed with acute lymphoblastic leukemia (ALL) are considered the patient subgroup at the highest risk for central nervous system (CNS) disease, both at presentation and as an isolated extramedullary relapse. In addition, they are highly vulnerable to adverse developmental sequelae from CNS-directed therapy.. Thirty patients younger than 12 months at diagnosis (12 males, 18 females) in first hematologic remission were evaluated after completion of ALL therapy (mean age = 62.1 months; standard deviation = 17.2 months; range = 38-102 months). CNS-directed treatment included very high dose infusions of methotrexate (MTX) and intrathecal cytarabine and MTX. Three patients had meningeal leukemia that required additional therapy. Children were administered the McCarthy Scales of Children's Abilities, and parents completed a sociodemographic questionnaire to obtain information about occupation and education.. Mean scores on all 6 cognitive and motor indices of the McCarthy Scales were in the average range (Verbal = 52.0; Perceptual = 53.6; Quantitative = 49.6; General Cognitive Index [GCI] = 102.1; Memory = 49.2; Motor = 51.0). Score distributions for each neurodevelopmental index were comparable to age-based population standards. One patient obtained a GCI that exceeded 2 standard deviations above the mean; none scored more than 2 standard deviations below. There was no report of developmental disabilities or neurologic disorders for any of the patients. Risk factors, including age at diagnosis, gender, additional CNS-directed treatment, and family socioeconomic status, were not associated with developmental outcome.. Test findings indicated a generally positive neurodevelopmental outcome for ALL patients diagnosed in infancy who were treated with very high dose MTX as CNS-directed therapy. Combined with the reduction in the isolated CNS relapse rate achieved by the Children's Cancer Group (CCG) clinical trial CCG-107, the results of this study represent a substantial improvement in neurodevelopmental outcome for very young patients compared with infants treated for ALL in the past.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Brain Damage, Chronic; Cognition Disorders; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Developmental Disabilities; Female; Follow-Up Studies; Humans; Infant; Injections, Spinal; Leucovorin; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Movement Disorders; Neuropsychological Tests; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Psychomotor Performance; Remission Induction; Risk; Socioeconomic Factors; Survivors; Vincristine

In the group of 75 ALL patients treated between 1980 and 1989, two women (ages 25 and 17, both FAB-L2 and CALLA +, after 56 and 34 months of continuous CR, respectively) were found to have a relapse manifested as a local infiltration of skin, with involvement of the adjacent lymph nodes in one patient. The leukaemic character of the skin infiltration was confirmed by skin needle aspiration and tissue biopsy expressing CD10 and CD24. Both patients were given intensified systemic chemotherapy and local X-ray irradiation. Complete remission was obtained with the disappearance of the skin infiltrations followed after 13 and 8 months, respectively, followed by a marrow relapse with symptoms of CNS involvement in one case. Both patients died because of treatment resistance (the overall survival time equalled 70 and 44 months, respectively).

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Cyclophosphamide; Cytarabine; Doxorubicin; Female; Humans; Immunotherapy; Leukemic Infiltration; Mercaptopurine; Methotrexate; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Radiotherapy; Recurrence; Remission Induction; Skin; Vincristine