Secondary leukemia responsive to retinoic acid with abnormal localization of RARalpha protein: a report of two cases.
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Adult↗
Biomedical subjects
S Sica
Publications and source records attributed to S Sica.
Acute myeloid leukemia after iodine-131 treatment for thyroid disorders.
Leukemia has rarely been reported as a late complication of 131I therapy, occurring mostly after cumulative doses of 800 mCi. We observed two cases of acute myeloid leukemia (AML) after 131I therapy for hyperthyroidism and thyroid carcinoma, respectively. The first patient was a 45-year-old woman treated with a single dose of 27 mCi 131I for hyperthyroidism. She developed AML (FAB M2) 14 months after receiving 131I; the second patient was a 44-year-old man affected by refractory thyroid carcinoma who received a total dose of 1 Ci 131I plus radiotherapy and developed AML (FAB M6) 8 years after the first exposure to 131I. Although it is a very rare event, the occurrence of leukemia after 131I treatment should be kept in mind, considering the widespread use of 131I, particularly in the treatment of hyperthyroidism, and the unfavorable outcome of secondary leukemia.
Acute Disease↗
Highly fluorescent reticulocytes after CD34+ peripheral blood progenitor cell transplantation.
Highly fluorescent reticulocyte (HFR) counts were evaluated in 13 consecutive patients affected by hematological malignancies and submitted to autologous selected CD34+ peripheral blood progenitor cell (PBPC) transplantation. Results were compared with a historical group of patients comparable for age, disease and conditioning regimen submitted to unfractionated PBPC transplantation. HFR counts of the CD34+ group declined to an undetectable level from day +4 to day +10 when they became detectable and reached 5% of total reticulocyte count by day +12. In the historical group, the nadir was identical but the recovery was faster (day +9). Total reticulocyte count > 1% was achieved at days +17 and +11, respectively. The absolute neutrophil count (ANC) recovery was identical in both groups, achieving a value > 0.5 x 10(9)/l at day +13 after reinfusion. Hence, in the historical group, HFR count gave advance notice of complete and stable hemopoietic engraftment while in the CD34+ group HFR and ANC count showed almost simultaneous recovery.
Adult↗
Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation.
Prevention of uterine bleeding after stem cell transplantation was attempted in 30 consecutive premenopausal women affected by hematological malignancies. This was with luteinizing hormone-releasing hormone (LHRH) leuprorelin acetate depot 3.75 mg administered subcutaneously at least 30 days before the conditioning regimen and then 28 days after the first dose. Complete prevention resulted in all but one patient (96.5%) during the phase of profound thrombocytopenia. No side-effects related to leuprorelin were observed. All patients developed amenorrhea after transplantation. Gonadal function was periodically assessed by means of luteinizing hormone (LH), follicular stimulating hormone (FSH) and estradiol serum levels. Hormone levels were consistent with menopause in all patients. After transplantation, patients required hormone replacement with estroprogestinics or estrogens alone when indicated. Leuprorelin is highly effective in preventing uterine bleeding in premenopausal women undergoing stem cell transplantation and has an excellent toxicity profile and virtually no interface with hemostatic balance and hepatic function. The role of leuprorelin in gonadal protection is currently unclear and deserves further investigations.
Adolescent↗
Long-lasting complete remission in plasma cell leukemia after aggressive chemotherapy and CD34-selected autologous peripheral blood progenitor cell transplant: molecular follow-up of minimal residual disease.
Plasma cell leukemia is a rare disease associated with very poor survival with standard treatment. We report a patient affected by plasma cell leukemia treated with aggressive chemotherapy and autologous CD34-selected PBPC who achieved a complete remission now lasting more than 2 years. Molecular studies confirmed the presence of minimal residual disease (MRD) despite the absence of disease activity. High-dose chemotherapy with stem cell rescue may be applied to selected patients considering the impact of the treatment on survival. The meaning of molecular MRD in this setting is unclear.
Antigens, CD34↗
Infectious complications after CD34-selected autologous peripheral blood stem cell transplantation.
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Adult↗
The Hohn catheter in the management of haemopoietic stem cell transplant recipients.
Patients undergoing bone marrow transplantation require a reliable venous access. The authors have tested the feasibility and safety of a new, silicone, open-ended, non-tunnelled central venous catheter (CVC), the Hohn catheter (Bard Access System, USA). From January 1994 to December 1996, 58 Hohn were inserted into 56 bone marrow transplant (BMT) patients (26 women: 30 men; mean age 38 years, range 19-62 years). The CVC was inserted percutaneously at the bedside by puncture of the subclavian or the internal jugular vein. No early complications were observed. Significant late complications were infection (documented only in 14%) and accidental removal (11%). The median life of the CVC was 30 days (range 15-180 days). Major causes of removal were end of use (25 patients) and fever (19 patients; but infection was documented only in eight patients). In spite of the relatively small gauge (5 Fr), the Hohn catheter was adequate for rapid or high density infusion. In our experience, the unique features of the Hohn CVC (versatility, optimal biocompatibility, bedside management, low cost) may contribute to making the BMT procedure safer and less expensive.
Adult↗
Incidence of sepsis after peripheral blood progenitor cells transplantation: analysis of 86 consecutive hemato oncological patients.
The incidence of documented infections after autologous peripheral blood progenitor cells transplantation (PBPCT) was retrospectively evaluated in 86 consecutive patients (47 males 39 females; median age 36 years, range, 18-63) treated in our institution; 83 patients had refractory hematological malignancies (40 non-Hodgkin's lymphoma, 19 Hodgkin's disease, 17 multiple myeloma, 7 acute myeloblastic leukemia) and 3 had solid tumors (1 rabdomyosarcoma, 1 neuroblastoma, 1 osteosarcoma). All patients developed fever after transplantation lasting a median of 2 days (range 1-17); 20 instances of documented sepsis developed in 17 patients (19.7%). Gram positive microorganisms were implicated in all but 4 cases. There were no fatalities directly due to infections and no correlation was found between the risk of infection and reaching PMN > 0, 1 x 10(9)/L, PMN > 0.5 x 10(9)/L. In addition no specific risk factors related to age, disease, conditioning regimen, use of central venous catheter (CVC), type of transplant, and isolation measures were identified.
Adolescent↗
Immunophenotypic profile of peripheral blood eosinophils in acute graft-vs.-host disease.
We used a flow cytometry technique, the "FOG" method (formaldehyde and octylglucopyranoside), to investigate the expression of activation antigens, i.e., CD4, CD23, CD25, HLA-DR, and the EG2 epitope of eosinophilic cationic protein, on peripheral blood eosinophils (PBEs) in leukemic patients who had developed acute graft-vs.-host disease (aGVHD) with eosinophilia after allogeneic bone marrow transplantation (alloBMT) or leukocyte buffy coat infusion. A comparative analysis was performed in transplanted patients not affected by aGVHD and in other conditions commonly associated with peripheral eosinophilia, i.e., interleukin (IL)-2 immunotherapy and allergy. CD25, recognizing the p55 subunit of IL-2 receptor, was detected in all patients with aGVHD except two who, at the onset of eosinophilia, were already receiving methylprednisolone intravenously. The specificity of our findings is confirmed by the absence of reactivity with anti-CD25 mAb in PBEs from transplanted patients not affected by aGVHD. Interestingly, the expression of CD25 progressively declined after steroid therapy. CD25 was also expressed after rhIL-2 administration, probably reflecting analogous mechanisms of eosinophil activation. No aGVHD or rhIL-2-treated patient showed reactivity with anti-CD4, CD23, or HLA-DR. CD25 and CD23 antigens were detected in 29% and 36% of allergic patients only. The accessibility of the EG2 epitope was significantly enhanced in all study groups compared with controls. In vitro activation of normal eosinophils with phorbol 12-myristate 13-acetate upregulated CD9 and EG2 expression but failed to induce the CD25 antigen, suggesting that selective activating stimuli may be required. The functional significance of in vivo CD25 expression and the role of activated PBEs in the development of cellular and cytokine-mediated tissue destructive processes in aGVHD remain to be clarified.
Adolescent↗
Assessment of hematological and immunological function during long-term follow-up after peripheral blood stem cell transplantation.
BACKGROUND AND OBJECTIVE: Long-term hemopoietic and immunological profile after autologous peripheral blood progenitor cells transplantation (PBPCT), in patients affected by hematological malignancies is largely unknown. The aim of this work was to detect the impact of high dose chemotherapy and PBPCT on hemopoietic and immunological function compared to conventional chemotherapy. DESIGN AND METHODS: Patients had to fulfill the following criteria: continuous complete remission after PBPCT, follow-up longer than 12 months, no chemo or radiotherapy or biological response modifiers after PBPCT. Twenty-five patients were considered eligible for this analysis. Stable and complete hemopoietic reconstitution (Hb > 12 g/dL, WB > 4.0 x 10(9)/L, ANC > 1.5 x 10(9)/L and Pits count > 150 x 10(9)/L), morphological examination of peripheral blood and bone marrow, cytogenetic analysis and immunological profile were evaluated at 12 months and yearly thereafter. RESULTS: Immunological reconstitution showed a persistent reduction of CD4/CD8 ratio up to five years after PBPCT. This reduction was related to a persistent increase of CD8+ lymphocytes and a constant reduction of CD4+ lymphocytes. INTERPRETATION AND CONCLUSIONS: Defects observed in PBPCT patients are induced by the procedure itself, by the conditioning regimen or both. The different behavior in the immune reconstitution of CD8+ subset after PBPCT may be favored by an extrathymic origin of these cells while CD4+ subset recovery which is thymus-dependent is impaired after PBPCT in adult population. Long-term hemopoietic reconstitution after PBPCT is rapidly obtained and is stable over the years, long-term immunological function seems to be abnormal in these patients and these abnormalities are long-lasting.
Adult↗
Serum of healthy donors receiving granulocyte colony-stimulating factor induces T cell unresponsiveness.
The effects of serum from healthy donors receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF) (G-serum) on blast transformation, expression of activation-related antigens, secretion of interleukin (IL)-2, and proliferation were evaluated in allogeneic lymphocytes stimulated with phytohemagglutinin. Escalating concentrations of G-serum induced 27%, 47%, and 70% suppression of lymphocyte proliferation; interestingly, CD4+ and CD8+ cells underwent blast transformation and up regulated early (CD69) and late (CD25, HLA-DR, and CD71) activation-related antigens. Negligible fractions of apoptotic cells were found after mitogenic challenge, suggesting that the strongly diminished proliferation was not attributable to extensive activation-induced programmed cell death of responding T cells. The levels of IL-2 in cultures containing G-serum were comparable to those in cultures performed without G-serum; however, high concentrations of exogenous IL-2 restored lymphocyte mitogenesis regardless of G-serum concentration. These findings--cell enlargement, upregulation of activation-related antigens, inability to proliferate after mitogenic stimulus, and restoration of cell division by exogenous IL-2--resembled those associated with "partial activation" of lymphocytes, a fundamental control mechanism of tolerance induction in T cell clones. Soluble immunoregulatory mediators infused with allogeneic hematopoietic progenitor products collected after rhG-CSF administration could induce T cell unresponsiveness in vivo, thus preventing clonal expansion and amplification of immune responses, and could account for the unexpectedly reduced incidence and severity of graft vs. host disease compared with allogeneic marrow infusion.
Adult↗
Inhibition of lymphocyte blastogenic response in healthy donors treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF): possible role of lactoferrin and interleukin-1 receptor antagonist.
The effects of rhG-CSF on lymphocyte blastogenesis were evaluated in six healthy donors, submitted to progenitor cell mobilization for allogeneic transplantation. Neutrophil, monocyte and lymphocyte count increased 6.7-fold, 5.3-fold and 2.0-fold on day +4 of rhG-CSF as compared with baseline. The DNA stimulation index (DNA SI) of 72 h phytohemagglutinin (PHA)-treated cultures decreased from 20% (15-35.5) prior to rhG-CSF to 6.7% (1.5-11.9; P = 0.0026), 8% (4-12; P = 0.0091) and 15% (9-22; P = 0.0091) on days +2, +4 and +6; similarly, reactivity to concanavalin A decreased from 18% (12-20) to 1.8% (0.5-7; P < 0.01), 3% (2-8; P < 0.01) and 5% (2-11; P = 0.009). No changes of lymphocyte response to pokeweed mitogen were observed. DNA SI of PHA-treated cultures inversely correlated with neutrophil and monocyte count. IL-1 receptor antagonist (IL-1ra) and lactoferrin (Lf) plasma levels sharply increased and correlated with neutrophil and monocyte count. IL-10 increased five-fold on day +2, returned to pretreatment values thereafter and did not show any correlation with DNA SI, suggesting that it was not responsible for the observed phenomena. Interestingly, DNA SI of PHA-treated cultures inversely correlated with IL-1ra and Lf levels. CD3+ and CD19+ lymphocyte activation status, ie CD23, CD25, CD30 and HLA-DR coexpression, was not affected by rhG-CSF administration. Pharmacological doses of rhG-CSF in healthy donors inhibit lymphocyte blastogenesis via an increased production and/or release of immunoregulatory soluble mediators, ie IL-1ra and Lf, by primed neutrophils and monocytes.
Adult↗
Autologous stem cell transplantation: evaluation of erythropoietic reconstitution by highly fluorescent reticulocyte counts, erythropoietin, soluble transferrin receptors, ferritin, TIBC and iron dosages.
The plasma concentrations of erythropoietin (Ep), soluble transferrin receptors (sTfRs), iron, total iron binding capacity (TIBC) and ferritin were monitored in five leukaemia patients undergoing autologous bone marrow stem cell transplantation (BMSCT) and in 10 lymphoma and 21 ovarian cancer patients undergoing autologous peripheral blood SCT (PBSCT); 9/21 ovarian cancer patients received recombinant human G-CSF and Ep and six recombinant human GM-CSF and Ep following SCT. All parameters were evaluated in relation to the kinetics of erythroid reconstitution as evaluated by haemoglobin (Hb) and reticulocyte levels [including the fraction of immature reticulocytes, also called highly fluorescent reticulocytes (HFR)]. Leukaemia patients undergoing BMSCT showed only a delayed (occurring at days 35-50 after SCT) and partial RBC, neutrophil and platelet recovery, whereas all patients undergoing PBSCT exhibited a rapid (occurring at days 10-15 after SCT) and sustained haemopoietic recovery. The various levels of erythroid rescue observed among these patients markedly influenced the kinetics of the different parameters investigated: (i) in leukaemia BMSCT patients sTfRs declined following SCT and remained at low levels thereafter, whereas Ep, iron. TIBC and ferritin showed a progressive and significant increase; (ii) in the different groups of patients undergoing PBSCT: (a) sTfR levels first declined following SCT and then returned to pre-therapy values at days 12-16, this response preceded erythropoietic recovery; (b) Ep, total iron, TIBC and ferritin showed an initial increase in the first days following SCT and then returned to pre-therapy values. Altogether, these observations indicate that: (i) both sTfR levels and reticulocyte counts are predictive parameters of erythropoietic recovery; (ii) coordinated changes of biochemical parameters underlying iron metabolism (iron, TIBC and ferritin) accompany erythroid rescue following SCT.
Adolescent↗
Evaluation of two different protocols for peripheral blood stem cell collection with the Fresenius AS 104 blood cell separator.
OBJECTIVES: Reconstitution of hematopoiesis by means of peripheral blood stem cells is a valid alternative to autologous bone marrow transplantation. The aim of this investigation was to increase the efficiency of collection of circulating blood progenitor cells and to obtain a purer product for transplant. METHODS: We carried out leukapheresis procedures with the Fresenius AS 104 blood cell separator, using two different protocols, the previously used PBSC-LYM and a new mononuclear cell collection program. RESULTS: Both programs were highly effective in collecting mononuclear cells (MNC) and CD34+ cells. Some differences were found, especially regarding MNC yield and efficiencies. There are remarkable differences in the efficiency of collection of CD34+ cells (62.38% with the new program as opposed to 31.69% with the older one). Linear regression analysis showed a negative correlation between blood volume processed and MNC efficiency only for the PBSC-LYM program. Differences were also observed in the degree of inverse correlation existing in both programs between patients' white blood cell precount and MNC collection efficiency. The inverse correlation was stronger for the PBSC-LYM program. Seven patients with solid tumors and hematologic malignancies received high dose chemotherapy and were subsequently transplanted with peripheral blood stem cells collected using the new protocol. All patients obtained a complete and stable engraftment with the reinfusion product collected with one or two leukapheresis procedures. CONCLUSIONS: High efficiencies and yields were observed in the new protocol for MNC and CD34+ cells. These were able to effect rapid and complete bone marrow recovery after myeloablative chemotherapy.
Adolescent↗
The role of bronchoalveolar lavage in the microbiological diagnosis of pneumonia in patients with haematological malignancies.
In the aetiological diagnosis of pulmonary infections in patients affected by haematological malignancies we evaluated the utility of bronchoalveolar lavage (BAL). One hundred and twenty-seven BAL were performed in 119 patients. In our series, we identified the agent of pneumonia in 53.5% of episodes with the best results in aspergillosis, very common in these patients. The previous empirical anti-infective treatment was modified in 14 episodes (11%). The procedure was generally well tolerated and only one patient bled. We maintain that BAL is a useful diagnostic tool for detecting the agents of pulmonary infections in patients with haematological malignancies, especially when the routine microbiological procedures fail, and it also represents a good alternative to more invasive procedures.
Adolescent↗
Extramedullary relapse in acute promyelocytic leukemia.
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Antineoplastic Agents↗
Growth factor administration following autologous peripheral blood progenitor cell transplantation.
Hematopoietic growth factor (HGF) administration following autologous peripheral blood progenitor cell transplantation (APBPCT) is a current approach for shortening the duration of high-dose chemotherapy-induced transient peripheral pancytopenia. Several published clinical experiences and a retrospective study reported here show that recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration potentiates polymorphonuclear leukocyte (PMN) and white blood cell (WBC) recovery with some clinical benefits mainly related to the reduction of infectious complications during the shortened period of neutropenia. However, this therapeutic strategy does not produce any enhancement of platelet (PLT) recovery or potentiation of red cell production. Conversely, a recent phase I/II study carried out in our institution showed that the combined administration of rhG-CSF and recombinant human erythropoietin (rhEPO) is able to potentiate trilineage hematopoietic recovery with a reduction of PLT transfusions and to considerably simplify the clinical management of patients as compared to patients treated with APBPCT alone. The post-APBPCT administration of rhEPO with rhGM-CSF decreased the number of days with WBC < 1 x 10(9)/L but failed to produce any appreciable effect on PLT recovery. Both combined treatments significantly reduced the patients' hospital stay and allowed the abrogation of systemic antibiotic administration following APBPCT. A further group of patients were treated with the combined administration of rhEPO, rhG-CSF and rhGM-CSF; they did not show a faster hematopoietic recovery than rhG-CSF plus EPO treated patients and a consistent hyperthermia was observed in most patients as a prominent side effect. Future prospective randomized studies will clarify the efficacy of HGF administration following APBPCT. Moreover, further improvements in the hematopoietic support of transplanted patients may be obtained when stem cell factor, flt3/flk2 tyrosine kinase ligands or megakaryocyte growth and development factor will become clinically available.
Erythropoietin↗
Secondary leukemia after autologous peripheral blood progenitor cell transplantation for breast cancer.
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Adult↗