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Seven male patients in the David T Purtilo International X-linked Lymphoproliferative Disease (XLP) Registry have undergone allogeneic hematopoietic stem cell transplantation (HSCT). All patients received HSCT from HLA-identical donors: sibling BM, five; unrelated BM, one; and sibling umbilical cord blood, one. Ages at time of HSCT ranged from 5 to 30 years. Pre-HSCT clinical course varied, but four boys had a significant history of chronic and/or serious infections. Conditioning regimens varied: TBI containing regimens, four, chemotherapy only, three. All patients engrafted. Six developed grade I-II acute GVHD but no chronic GVHD. Four are alive and well with normal immune function greater than 3 years following HSCT. Three died within 100 days: disseminated adenovirus, one; polymicrobial sepsis, one; and multiple organ system failure and bleeding diathesis, one. No EBV-associated post-transplant complications were observed, even though all donors except the umbilical cord blood were EBV-seropositive. Unsuccessful HSCT was associated with age at HSCT (> 15 years), TBI-containing regimen and significant history for pre-HSCT infections. These results provide evidence that HSCT performed during childhood with HLA-identical sibling donors, regardless of EBV serostatus, offers the only curative therapy for XLP.

A 58-year old male with follicular small cleaved B cell lymphoma developed pure red cell aplasia (PRCA) during chemotherapy. To understand the etiology of the PRCA, we studied the effects of patient sera on the progenitor cell colony formation of normal human bone marrow cells in vitro. We demonstrated a marked inhibition of normal bone marrow progenitor cell colony formation by patient sera, but not pooled normal human sera. Immunoglobulin was then precipitated from patient sera for similar studies. The majority of the precipitated immunoglobulin was of the IgG type. The immunoglobulin fraction markedly inhibited normal bone marrow progenitor cell colony formation, whereas the non-immunoglobulin fraction was not inhibitory. The presence of inhibitory serum immunoglobulin correlated with the hematologic status of the patient. We conclude that the development of PRCA in patients with B cell lymphoma may be due to a serum IgG inhibitor of bone marrow progenitor cell growth.

The mechanisms responsible for the bone marrow failure in 21 aplastic anemia patients were studied by the colony-forming units in culture assay (CFU-C). Twelve patients had no detectable in-vitro defect that could be responsible for the low CFU-C numbers. Three patients had suppressor T cells that inhibited CFU-C (p less than 0.001); one of two patients responded to antithymocyte globulin therapy and the third recovered spontaneously. Three patients had serum inhibitory immunoglobulins directed against their marrow CFU-C; plasmapheresis resulted in recovery of bone marrow function. Three patients had abnormalities at the colony-stimulating factor level: Two had inhibitors of colony-stimulating factor, corrected in vitro and in vivo by indomethacin and cholinergic agonists (p less than 0.01); and the third had colony-stimulating factor generation defect, corrected in vitro and in vivo by lithium. Testing for cellular or humoral suppressor factors directed against precursor cells or for abnormalities at the colony-stimulating factor level gives helpful guidelines to therapy in aplastic anemia.

Of the first 14 patients with acute or chronic leukemia to undergo bone marrow transplantation at our hospital, 9 (64%), all good-risk, are still alive in remission at 18 to 42 months of follow-up (mean, 29 months) with their Karnofsky performance status between 80% and 100%. The conditioning regimen of fractionated-dose irradiation and high-dose chemotherapy eradicated their disease; only two patients relapsed after transplantation. Toxicity was acceptable. Acute graft-versus-host disease developed in six patients (43%) (grade I or II in four, grade IV in two) and progressed to chronic graft-versus-host disease in four. Viral pneumonitis developed in three patients (21%), but none had idiopathic interstitial pneumonitis. The mean hospital charge was $54,355. These preliminary results suggest that good-risk patients with acute or chronic leukemia can be treated with bone marrow transplantation in a university affiliated hospital with appropriate staff and support facilities and achieve results comparable to those in research institutions at a competitive cost.

Thrombocytopenia in patients with multiple myeloma is usually due to chemotherapy or marrow replacement with myeloma cells. Two patients with multiple myeloma who fulfilled criteria for the diagnosis of immune thrombocytopenic purpura are presented. The etiologic and therapeutic implications of this unusual association are discussed.

The purpose of this study was to determine whether the use of relatively small amounts of radiographic contrast agents may impair hemostasis. Before and after injection of contrast agents, we measured the template bleeding time, platelet count in whole blood and platelet-rich plasma, platelet aggregation induced by epinephrine and adenosine diphosphate (ADP), and percent disaggregation of ADP-induced platelet aggregates in platelet-rich plasma of 18 patients. Ten patients received 50-100 ml of sodium iothalamate (66.8%) for intravenous urography and 8 patients received 125-200 ml of a combination of meglumine diatrizoate (66%) and sodium diatrizoate (10%) for coronary angiography and left ventriculography. Neither group demonstrated a statistically significant mean difference (p greater than 0.05) for any parameter measured before and after administration of the contrast agents. However, 2 patients who received diatrizoate had lengthening of their bleeding times to greater than twice the baseline value without any change in in vitro platelet aggregation. Physicians should be aware of this potential cause of bleeding which could be of particular danger to patients undergoing cardiopulmonary bypass with its inherent hemostatic defects.