Pleocytosis after hemopoietic stem cell transplantation.

Frequency and clinical significance of cerebrospinal fluid (CSF) pleocytosis in hemopoietic stem cell (HSC) transplantation were surveyed. Cyclosporine (CSA)- or tacrolimus (FK506)-based regimens were used as graft-vs-host disease (GVHD) prophylaxis in allogeneic HSC transplantation. CSF pleocytosis with or without neurologic symptoms was detected in 12 of 25 patients receiving allogeneic HSC transplants but in none of 11 patients receiving autologous HSC transplants. Of the 12 patients with CSF pleocytosis, only one patient developed leukoencephalopathy later. There was a correlation between CSF cell numbers and trough levels of CSA but not with those of FK506. In patients receiving allogeneic HSC transplants, CSF pleocytosis may be relatively common and may reflect neurologic damage associated with calcineurin inhibitors.

Establishment and characterization of a new erythroblastic leukemia cell line, EEB: phosphatidylglucoside-mediated erythroid differentiation and apoptosis.

A new erythroblastic leukemia cell line (EEB) was established from a patient with early erythroblastic leukemia. The cells had features of immature erythroblasts, including an agranular basophilic cytoplasm and CD36, CD71, CD175s (sialyl-Tn) and CD235a (glycophorin A) expression without CD41 expression, myeloperoxidase activity and platelet-peroxidase activity. The cells were confirmed to be of the erythroid lineage based on expression of the gamma-globin message. They were induced to differentiate into benzidine-positive cells by hemin and delta-amino levulinic acid (delta-ALA). An analysis of cell membrane lipids showed that EEB cells contain a type of glycerolipid, phosphatidylglucose (PhGlc), but not unbranched type 2 chains, i antigens. GL-7 which is a recombinant Fab fragment of GL-2 and binds to PhGlc, induced production of hemoglobin F (HbF) associated with accumulation of the gamma-globin (gamma-globin) message in EEB cells. The GL-7-mediated erythroid differentiation was associated with apoptosis. These results suggest that direct signaling to PhGlc mediates erythroid differentiation and apoptosis in EEB cells.

Autologous gamete cryopreservation before hemopoietic stem cell transplantation.

BACKGROUND: Infertility after hemopoietic stem cell transplantation (HST) is a serious problem for young patients. Autologous gamete collection before HST may be a promising strategy to overcome infertility. MATERIAL/METHODS: From October 1988 to December 2003, six male and nine female patients with hematological malignancies had autologous gametes collected before HST. The data on autologous gamete collection were analyzed. RESULTS: Sperm could be collected from three patients. However, in two of the three, the numbers and motility of the sperm were severely depleted because they received chemotherapy for one and 11 cycles, respectively. Normal sperm was only collected from one patient with myelodysplastic syndrome who had no history of receiving chemotherapy. One or more oocytes could be collected in five of nine female patients, although the five received multiple cycles of chemotherapy. The successful oocyte collection was associated with an ovulation stimulant. CONCLUSIONS: Autologous oocye collection before HST may be possible, even if patients receive multiple cycles of chemotherapy. In contrast, autologous sperm collection before HST may be difficult after patients receive chemotherapy. Successful pregnancy using autologous gametes after HST remains extremely difficult, especially in female patients; however, it is important to give information on infertility and autologous gamete collection to patients scheduled for HST.

Involvement of the esophagus and stomach as a first manifestation of varicella zoster virus infection after allogeneic bone marrow transplantation.

A 46-year-old man with myeloproliferative disorder received a stem cell transplant from an HLA-identical unrelated donor. Eight months status post transplantation, during the course of tacrolimus therapy, the patient developed severe epigastric pain and fever. FGS findings showed eruptions with blisters in the esophagus and ulcers in the stomach. Biopsy specimens revealed acidophilic inclusion bodies in the nuclei. Varicella zoster virus (VZV) DNA copies were detected in the serum. No skin lesions were observed prior to hospital admission. The diagnosis of visceral VZV infection was made and the gastric and esophageal lesions were successfully healed with acyclovir (ACV). Severe abdominal pain is one of the most important signs of VZV infection for recipients of stem cell transplantation.

Severe hepatitis and complete molecular response caused by imatinib mesylate: possible association of its serum concentration with clinical outcomes.

A 40-year-old female with chronic myelogeneous leukemia (CML) in the chronic phase was treated with imatinib mesylate (STI571) because of interferon resistance. She achieved complete cytogenetic response but not complete molecular response 3 months after STI571 administration. Six months later, she developed severe liver damage without evidence of actively infectious hepatitis A, B, C, G, E, TT virus, Epstein-Barr virus or cytomegalovirus. A significant serum level of STI571 (107 ng/ml) was detected, although she had not taken the drug for 6 days. Liver biopsy demonstrated massive hepatic necrosis, consistent with drug-induced hepatitis. She achieved complete molecular response, although she did not take STI571 for 47 days after the development of hepatitis. These results suggest that both hepatitis and molecular response were associated with the serum STI571 concentration.

Paraproteinemia after hematopoietic stem cell transplantation.

The frequency and clinical significance of paraproteinemia in patients receiving hematopoietic stem cell (HSC) transplants were assessed. Of 66 patients with hematologic malignancies, excluding multiple myeloma who received an allogeneic or autologous HSC transplant, paraproteins were detected in 12 patients using immunoelectrophoresis. None of the patients showed paraproteinemia before HSC transplantation. The class of paraproteins most commonly seen was IgG. In 9 of these 12 patients (75%), a paraprotein was detected continuously after HSC transplantation for an average duration of 464 days, while others demonstrated a transient appearance of the protein. Paraproteinemia after HSC transplantation was not related to the stem cell source, (allograft vs. autograft), age, gender, viral infection and graft-vs.-host disease (GVHD). None of the patients developed plasma cell dyscrasia after the appearance of the paraprotein, while 1 patient developed secondary acute lymphoblastic leukemia. These findings indicate that paraproteinemia after HSC transplantation may be caused by an aberrant immune reconstitution after both allogeneic and autologous HSC transplantation. A long-term follow-up of patients with paraproteinemia after HSC transplantation is needed to confirm this finding in a larger series of patients.

[Successful treatment of refractory acute GVHD with mycophenolate mofetil after peripheral blood stem cell transplantation from the patient's one locus-mismatched mother].

A 35-year-old male with chronic myeloid leukemia in the accelerated phase received a peripheral blood stem cell transplant from his HLA-DR-mismatched mother. Graft-versus-host disease (GVHD) prophylaxis was with short-term methotrexate and tacrolimus. After transplantation, grade II skin acute GVHD occurred and was unsuccessfully treated with bolus methylprednisolone administration. The acute GVHD progressed to grade III of the skin, gut and liver, and mycophenolate mofetil (MMF) was accordingly administered at a daily dose of 2 g. This treatment resulted in a dramatic improvement in the clinical features of the acute GVHD. The patient suffered from hemorrhagic cystitis and several episodes of cytomegalovirus antigenemia. MMF may be useful for steroid-resistant acute GVHD despite an increasing risk of viral infections.

Massive immune hemolysis after non-myeloablative allogeneic peripheral blood stem cell transplantation with minor ABO-incompatibility.

A 35-year-old male, blood group B, Rh(D)+ type, received an allogeneic peripheral blood stem cell (PBSC) transplant after a non-myeloablative regimen of fludarabine and cyclophosphamide for resistant gammadelta cutaneous T-cell lymphoma (CTCL). The donor was his HLA-identical brother, blood group O, Rh(D)+ type. Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporine alone. On day +8, massive immune hemolysis occurred, followed by acute renal failure. Hemodialysis was performed eight times until recovery of renal function on day +24. The risk of delayed immune hemolysis after non-myeloablative allogeneic PBSC transplantation with minor ABO-incompatibility must be considered.

Two-color flow cytometry with a CD19 gate for the evaluation of bone marrow involvement of B-cell lymphoma.

The usefulness of two-color flow cytometry with a CD19 gate (CD19-FCM) for detecting clonal B-cells in the bone marrow was evaluated. Since kappa and lambda ratios analyzed in the bone marrow from healthy adults were within the range of 0.5-3.0, outside of this range was regarded as the existence of clonal B-cells. Mixing experiments in vitro showed that 10% or more of clonal B-cells contaminating normal bone marrow cells could be detected using CD19-FCM. Ninety-nine bone marrow samples from 60 patients with B-cell lymphoma were simultaneously analyzed using CD19-FCM and histologic examination of both bone marrow aspiration and core needle biopsy samples. The agreement of results obtained by both examinations was 82% (81/99). Discrepant results were found in 18 samples of 10 patients. All except one sample were positive for CD19-FCM analysis but negative for histologic examination and the conversion of CD19-FCM-positivity to CD19-FCM-negativity was associated with chemotherapy. These results suggest that CD19-FCM is useful for the evaluation of bone marrow involvement of B-cell lymphoma.