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PubMed1995

Acute lymphoblastic leukemia and the lymphoblastic lymphomas of childhood.

Recent advances in diagnosis, treatment, and tumor biology of the lymphoid blastic malignancies have challenged historical concepts and created a need for revised classification of these diseases. The authors review this material and present a classification relevant to current therapeutic protocols and available biological data. Further advances in understanding of these diseases can be anticipated, with possible further evolution of classification. The exact clinical role of sensitive studies to monitor residual disease during and after treatment remains to be established. These diseases may present difficult differential diagnostic problems. The importance of accurate diagnosis cannot be overemphasized, as highly successful but divergent treatments have evolved for these various hematopoietic diseases. Diagnostic problems are usually resolved with systematic analysis including careful morphology, cytochemistry, immunologic analysis, and addition of EM and other studies in selected circumstances.

Bone Marrow↗
PubMed1996

[Multiple intracerebral granulocytic sarcomas in a patient with chronic myeloid leukemia].

The authors describe a young man with known chronic myeloid leukemia who sought medical attention after a first episode of seizure. The hematologic investigation revealed hyperleukocytosis without evidence of blastic transformation in peripheral blood or bone marrow. Numerous intracerebral nodules, characterized pathologically as granulocytic sarcomas, were demonstrated by computed tomography and magnetic resonance imaging (MRI). The appearance of a granulocytic sarcoma in chronic myeloid leukemia is unusual, and location of the lesion in the central nervous system is rare. Follow-up MRI after treatment showed almost complete regression of all lesions. The radiologic features of this case are discussed with reference to others reported in the literature.

Adult↗
PubMed1996

Testicular extramedullary myeloid cell tumor in a patient with myelodysplastic syndrome.

We report herein a case of extramedullary myeloid tumor arising bilaterally in the testes of a 66-year-old man, who had previously been diagnosed with myelodysplastic syndrome. Light microscopy of the testicular neoplasm demonstrated a tumor composed of large, slightly polygonal cells with pale blue to weakly eosinophilic cytoplasm. The tumor cells were immunoreactive for CD45, myeloperoxidase, lysozyme, CD43, and MB2. Many of the cells also expressed chloroacetate esterase. Peripheral blood and bone marrow findings were consistent with chronic myelomonocytic leukemia (FAB-CMML), particularly in the most recent material, which showed clear cellular dysplasia and an increase in the percentage of blasts in the bone marrow (15% to 20% of all nucleated cells). This case of extramedullary myeloid tumor is unusual in view of the patient's age and the testicular location. It emphasizes the importance of including extramedullary myeloid tumor in the differential diagnosis of histologically undifferentiated large-cell tumors, as well as a need to use a broad panel of immunohistochemical stains in such cases.

Aged↗
PubMed1996

Elevation of cerebrospinal fluid soluble CD27 levels in patients with meningeal localization of lymphoid malignancies.

Diagnosis of meningeal localization of lymphoid malignancies by means of cytologic examination of the cerebrospinal fluid (CSF) can be difficult. Thus far no reliable CSF tumor markers have been identified. CD27 is a transmembrane disulfide-linked 55-kD homodimer present on most peripheral blood T cells and on a subset of B cells. CD27 is also expressed on human malignant B cells and high levels of soluble CD27 can be present in the serum of patients with B-cell malignancies. The aim of this study is to determine prospectively the diagnostic value of CSF sCD27 as a tumor marker in patients with meningeal localization of lymphoid malignancies. CSF sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value using receiver operator characteristics curves was found to be 10 U/mL. sCD27 levels were normal in all 50 control patients (lumbar disc protrusion) and in 39 of 40 samples obtained from patients with either solid tumors or acute myeloid leukemia. Of 104 CSF samples from 70 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) undergoing routine central nervous system (CNS) staging, sCD27 was false positive and false negative in only one sample each. In 70 samples from 45 patients suspected of meningeal localization of ALL or NHL, the sCD27 test had an excellent sensitivity (100%) and specificity (82%). In 7 patients with positive CSF studied longitudinally, sCD27 levels correlated very well with remission and relapse. sCD27 levels were not nonspecifically increased by the administration of cytostatic drugs. Finally, sCD27 was also elevated in the 4 patients studied with primary central nervous system lymphoma (PCNSL). CSF sCD27 is a promising tumor marker in patients with either meningeal localization of lymphoid malignancies or PCNSL, and can be useful in the differential diagnosis of CNS involvement by either lymphoid malignancies or solid tumors.

Adult↗
PubMed1996

Two serologic markers to monitor the engraftment, growth, and treatment response of human leukemias in severe combined immunodeficient mice.

We have investigated human lactate dehydrogenase (LDH) isoenzymes and human nuclear matrix protein 41/7 (NMP 41/7) as potential serologic markers to monitor the course of human leukemia in severe combined immunodeficient (SCID) mice. Following the transplantation of 10(6) human acute lymphoblastic leukemia (ALL) Nalm-6 cells, human specific LDH isoenzymes were measurable in the serum of SCID mice as early as 7 days after transplantation, although serum total LDH increased in some animals as early as 5 days after transplantation. Human NMP 41/7 was measurable in all animals at day 15 after leukemia cell injection. Serum levels of total LDH, human specific LDH and NMP 41/7 increased progressively over time, reaching total LDH levels as high as 50,000 U/L at day 25 after transplantation. To determine whether the levels of LDH and NMP 41/7 in serum were a reflection of human tumor burden, we studied these serologic markers in SCID mice bearing measurable subcutaneous human neuroblastoma tumors, or compared the serum levels of these markers with the number of human leukemia CD10+ cells in the bone marrow of the SCID mice. The serum levels of total LDH, human specific LDH isoenzymes, and NMP 41/7 correlated well with tumor burden, and they drastically decreased or disappeared from serum after the human leukemia or neuroblastoma cells were selectively killed with a single intravenous (IV) injection of 1 to 3 micrograms diphtheria toxin (DT) (the cellular receptor for DT is present on human cells, but not on mouse cells). Paraplegic mice with central nervous system leukemia completely recovered after DT treatment. We conclude that measurements of serum levels of total LDH, human LDH isoenzymes, and NMP 41/7 are sensitive, quantitative, rapid, and easy to perform serologic methods useful to monitor the engraftment, progression, and treatment response of human leukemia in SCID mice.

Animals↗
PubMed1995

[Pathological studies on the anti-invasive character of IL-6 gene transfected leukemia cells].

FBL-3 Leukemia cells transfected with IL-6 gene were expanded in vitro and inoculated into C57BL/6 mice subcutaneously. Tumor growth was observed and histologic analyses of the tumors in situ and the liver, spleen and bone marrow were performed at 14, 21, 28 and 35 days after inoculation. The mice inoculated with wild-type FBL-3 leukemia cells were used as the control. We found that the tumor invasiveness in the mice inoculated with FBL-3-IL-6+ occurred later than in the control group. The survival time of experimental mice was longer than in the control mice. The results demonstrated that inoculation of IL-6 high-secreting FBL-3 inhibited invasiveness of the leukemia cells, suggesting that the IL-6 gene transfected FBL-3 cells can be used as a vaccine to treat leukemia. The mechanism of the anti-invasiveness of IL-6 gene transfected leukemia cells needs further study.

Animals↗
PubMed1996

Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia.

Relapsed acute lymphoblastic leukemia (ALL) usually carries a dire prognosis. We evaluated the effectiveness and long-term complications of intensive rotational combination chemotherapy for late hematologic relapse (median, 16 months after elective cessation of therapy) among 34 children and young adults (ages 4 to 23 years). Concurrent central nervous system (CNS) relapse was present in 3 cases and testicular relapse in 4. Secondary therapy comprised an intensive five-drug reinduction (6 weeks) followed by continuation treatment with four drug pairs, rotated weekly in 4-week cycles over 120 weeks. Intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine) was given three times during reinduction and every 8 weeks during continuation. Treatment was electively discontinued at week 120 in the absence of detectable disease. Thirty-three patients (97%) attained a second complete remission. At a median follow-up of 9.3 years (range, 4.5 to 11.4), estimates of 5-year second event-free and overall survival (+/- SE) are 65% +/- 8% and 79% +/- 7%, respectively. Eleven patients had a second relapse (9 marrow, 2 testicular) and one developed secondary myeloid leukemia. There have been no CNS relapses or deaths in remission. Treatment was well-tolerated and was given largely on an outpatient basis. Late effects are primarily endocrinologic; one child had a second malignant solid tumor (presumed related to initial radiation therapy) that was treated successfully. Intensive treatment with alternating non-cross-resistant drug pairs for late hematologic relapses of ALL is effective and well-tolerated, and produces results similar to those achieved in patients with newly diagnosed ALL. Event-free survival compares favorably with reports of other relapse regimens, including those incorporating bone marrow transplantation.

Adolescent↗
PubMed1995

[Testicular relapse in acute lymphoblastic leukemia. The experience of a pediatrics service].

Testicular relapse in Acute Lymphoblastic Leukemia is a problem which has been developing more and more, as the therapeutic protocols of acute lymphoblastic leukemia are improving. Its appearance, specially during chemotherapy, makes the prognosis of the disease poorer. There have been some diagnostic methods, used in the screening of this situation. The use of more aggressive therapeutic protocols can lead to more encouraging results. The authors of the research present seven children with testicular relapse, which represent 17% of the total group of fourty one boys with acute lymphoblastic leukemia, treated at St. o Antonio Pediatric Ward. They analyse the time of onset, the diagnostic approach of the testicular lesion, the therapeutic protocols chosen for each case and the results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Facial nerve palsy as an early manifestation of relapse in T-cell acute lymphoblastic leukemia.

We describe a 14-year-old girl with T-cell acute lymphoblastic leukemia (ALL) who developed peripheral type facial palsy alternately on each side during remission. The cerebrospinal fluid examination and imaging studies of the brain including the temporal area failed to identify the etiology. Fully 10 weeks after the onset of the facial nerve palsy, she showed cytological findings of meningeal and bone marrow relapse. Review of the literature revealed that an isolated facial nerve palsy due to leukemic cell infiltration is a rare occurrence. Nonetheless one needs to keep in mind that it may represent the initial sign of a relapse in a patient with leukemia, particularly with T-cell ALL.

Adolescent↗
PubMed1996

Central nervous system relapse after bone marrow transplantation for acute leukemia in first remission.

Four hundred and eighty-seven patients undergoing allogeneic or autologous BMT for acute leukemia in first remission received no prophylactic intrathecal chemotherapy after BMT. The conditioning regimen included total body irradiation in 433 (89%). Patients with acute lymphoblastic leukemia received cranial irradiation if they had no central nervous system (CNS) disease and all patients with CNS disease received craniospinal irradiation. Eleven of 311 patients examined had CNS disease at presentation, but none had active CNS disease at the time of BMT. Lumbar punctures were performed in 93 patients 1-2229 days (median 98) after BMT because of suspected CNS infection, hemorrhage or relapse (n = 65), or after systemic relapse (n = 28). CNS disease was seen in seven patients at 217-1209 days (median 340), none of whom had CNS disease pre-transplant. Systemic relapse had preceded CNS relapse by 4-207 (median 128) days in all seven and no isolated CNS relapse was seen. The actuarial risk of CNS and systemic relapse at 5 years was 2.9 and 35.9%, respectively. We conclude that CNS relapse is uncommon after BMT for acute leukemia in first remission, and that isolated CNS relapse is likely to be extremely uncommon. Therefore, routine prophylactic intrathecal chemotherapy is not warranted after BMT for acute leukemia in first remission.

Actuarial Analysis↗
PubMed1996

T cell-depleted allogeneic bone marrow transplantation from a partially HLA-mismatched unrelated donor for progressive chronic lymphocytic leukemia and fludarabine-induced bone marrow failure.

A 49-year-old man with a 3-year history of chronic lymphocytic leukemia (CLL, stage B at diagnosis) responded well to four course of fludarabine, but developed marrow failure and prolonged pancytopenia lasting 9 months following the fifth course. Fludarabine therapy could not be continued due to pancytopenia, eventually resulting in disease progression. Bone marrow transplantation from an unrelated donor mismatched at one DRB1 locus and both DQB1 loci was performed as salvage therapy. The marrow was depleted of T cells with Campath-1G. Pre-transplant immunosuppression was enhanced with 600 cGy total lymphoid irradiation and Campath-1G infusions in addition to 120 mg/kg cyclophosphamide and 1200 cGy fractionated total body irradiation. Cyclosporine alone was used as post-transplant immunosuppression. Neutrophils reached 0.5x10(9)/1 on day 14 and platelets 50 x 10(9)/1 on day 40. No acute graft-versus-host disease was seen. Bulk disease detected on CT scanning prior to BMT was found to have disappeared 10 weeks after BMT. The marrow showed residual disease (5% CD5+/CD19+ cells) 9 weeks after transplantation, which had decreased markedly at 13 (0.5%) and 26 (0.4%) weeks. The patient is currently alive and well 10 months after BMT with no clinically detectable disease. We conclude that BMT from an unrelated donor is a feasible treatment option in advanced CLL.

Antineoplastic Agents↗
PubMed1996

Minimally differentiated acute myeloid leukaemia revealed by specific cutaneous lesions.

Minimally differentiated acute myeloid leukaemia (AML-MO) is a poorly differentiated type of acute myeloid leukaemia. Its myeloid differentiation can only be demonstrated by the immunohistochemical or ultrastructural finding of cytoplasmic myeloperoxidase in bone marrow blasts and/or by the immunohistochemical expression of at least one lineage-specific myeloid antigen, with no reactivity for lymphoid antigens. We describe a man with a cutaneous nodular eruption that represented the first clinical manifestation of AML-MO. Histological examination showed extensive proliferation of blasts with scant basophilic cytoplasm. Immunohistochemically, these expressed neither myeloid nor lymphoid-specific antigens, whereas they were focally positive for CD45. The diagnosis of AML-MO was confirmed by immunophenotypic analysis of a bone marrow smear. A complete remission was achieved following parenteral steroid therapy. The disease relapsed some months later, and the patient died within a few weeks.

Acute Disease↗