Laboratory preparation of a deglycosylated ricin toxin A chain containing immunotoxin directed against a CD7 T lineage differentiation antigen for phase I human clinical studies involving T cell malignancies.

An immunotoxin consisting of a monoclonal antibody specific for CD7, a cell surface determinant expressed on T acute lymphocytic leukemia (T-ALL) blast cells, was linked to the potent plant toxin deglycosylated ricin toxin A chain (dgRTA) and is currently under evaluation in phase I clinical trials. Scale-up production of this immunotoxin, called DA7, was simplified using a two-step purification protocol that resulted in a highly purified immunotoxin meeting FDA criteria for IND approval. The anti-CD7 antibody, 3Ale, an IgG2b, was coupled to toxin using two different heterobifunctional cross-linkers, (1) N-succinimidyl-3-(2-pyridyl-dithiolproprionate) (SPDP), considered a standard croslinker and (2) 4-succinimidyloxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio)tolu ene (SMPT), designed to hinder the in vivo breakdown of the toxin/antibody disulfide bond.

Acute leukemia and the transient myeloproliferative disorder associated with Down syndrome: morphologic, immunophenotypic and cytogenetic manifestations.

Individuals with Down syndrome have an increased incidence of leukemia compared to the general population. In addition, Down syndrome children may acquire a myeloproliferation that resembles acute leukemia that undergoes a spontaneous, durable remission. To clarify the relationship between these two disorders, the morphologic, immunophenotypic and cytogenetic characteristics of 28 patients with Down syndrome and the morphologic manifestations of acute leukemia were examined.

Clinical characteristics of post-transplant lymphoproliferative disorders.

Purpose: To study the histopathologic findings, clinical course, and therapeutic outcome of patients who developed a lymphoproliferative disorder after undergoing solid organ transplantation.

Patients And Methods: A series of 26 patients who developed a lymphoproliferative disorder after solid organ transplant during a 27-year period were studied.

Results: The 26 patients ranged in age from 6 to 68 years (median 42 years).

Late-developing Philadelphia chromosomes in a case of T-cell acute lymphoblastic leukemia.

A child with T-cell acute lymphoblastic leukemia (ALL) is presented who at relapse acquired two Philadelphia chromosomes (Ph). Molecular studies at relapse revealed a rearrangement of the major breakpoint cluster region (M-bcr) on chromosome 22. No rearrangements of the immunoglobulin heavy chain or T-cell beta receptor gene loci were demonstrated.

L3 acute lymphoblastic leukemia. Comparison with small noncleaved cell lymphoma involving the bone marrow.

The relationship between acute lymphoblastic leukemia (ALL-L3) and stage IV small noncleaved cell lymphoma with bone marrow involvement (SNCL) was analyzed by retrospective study of 45 patients. Twelve patients with ALL-L3 had tumour restricted to the marrow and blood with no evidence of an extramedullary tumor at their initial presentation. Nineteen patients with stage IV SNCL had evidence of extramedullary disease in addition to marrow and blood involvement.