Experimental hematology
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Experimental hematology · Dec 1995
Case ReportsAllogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes.
Allogeneic bone marrow transplantation (BMT) is the treatment of choice for hematologic malignancies resistant to conventional chemotherapy and for patients who are at high risk for relapse. Until recently, no cure could be offered to patients relapsing following allogeneic BMT. We present our long-term observations of the first patient with remission reinduced by allogeneic cell therapy (allo-CT) using donor peripheral blood lymphocytes (PBL). ⋯ Although GVHD was frequent among responders, accompanied occasionally by transient or irreversible marrow aplasia, remissions were also obtained in patients with no GVHD. Allo-CT should therefore be considered as treatment of choice for overt relapse or de novo minimal residual disease post-BMT. Administration of donor peripheral blood lymphocytes in graded increments at an early stage of relapse may be the best approach for combining optimal timing at the stage of minimal disease while controlling and minimizing the risk of GVHD on an individual basis.
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Experimental hematology · Dec 1995
Comparative StudyEilatin: a novel marine alkaloid inhibits in vitro proliferation of progenitor cells in chronic myeloid leukemia patients.
We examined the effect of Eilatin, a novel marine product, on the survival of human myeloid progenitor cells (CFU-C) isolated from normal individuals and from 12 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the effect of interferon-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin, IFN-alpha, and Ara-C inhibited the proliferation of CFU-C from normal individuals and CML patients in a dose-dependent manner. ⋯ BCR/ABL translocations were detected in 94.6 +/- 0.6% of CD34+ cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion signals detected after exposure of CD34+ cells for 16 hours to Eilatin 10(-7) M, IFN-alpha 500 U/mL, or Ara-C 10(-9) M were 54.5 +/- 5%, 63.6 +/- 5%, and 70 +/- 4%, respectively (mean +/- SE, n = 5). Our data indicate that Eilatin, a substance isolated from the Red Sea purple tunicate Eudistoma sp., has an antileukemic effect against in vitro Ph+ cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or PB of CML patients in conjunction with autologous bone marrow transplantation.
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Experimental hematology · Dec 1995
Comparative StudyDetection of bcr-abl mRNA in single progenitor colonies from patients with chronic myeloid leukemia by PCR: comparison with cytogenetics and PCR from uncultured cells.
Bone marrow and/or peripheral blood of patients with chronic myeloid leukemia (CML) was investigated by the following three parameters: Ph' chromosome, bcr-abl expression in fresh blood and/or bone marrow, and bcr-abl expression in single hematopoietic progenitor colonies generated from blood and/or bone marrow. Expression of bcr-abl was proven by a reverse "nested primer" polymerase chain reaction (PCR) that is able to detect 1 pg of hybrid mRNA. We performed 108 investigations on 68 patients containing all three parameters: 12 on untreated patients, seven after interferon-alpha (IFN-alpha), seven after low-dose cytosine arabinoside (Ara-C), 22 after cyclic high-dose hydroxyurea (HU), 49 after allogeneic BMT, five before and three after stem cell mobilization, and three after autologous stem cell transplantation (ASCT). ⋯ The value of these observations is not clear. A follow-up of the patients will show if such sleeping progenitors can be activated in vivo. Concluding our observations, we can say that in special cases (therapy follow-up, detection of minimal residual disease) it could be useful to perform a PCR analysis of single progenitors in parallel with the routine investigations.
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Experimental hematology · Dec 1995
Proliferative response of human marrow myeloid progenitor cells to in vivo treatment with granulocyte colony-stimulating factor alone and in combination with interleukin-3 after autologous bone marrow transplantation.
We have recently reported that the hematologic recovery of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) undergoing autologous bone marrow transplantation (BMT) is significantly faster when recombinant human interleukin-3 (rhIL-3) is combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in comparison with patients receiving G-CSF alone. In this paper, we studied the kinetic response and concentration of BM progenitor cells of 17 patients with lymphoid malignancies submitted to autologous BMT and treated with the G-CSF/IL-3 combination. The results were compared with those of five lymphoma patients receiving the same pretransplant conditioning regimen followed by G-CSF alone. rhG-CSF was administered as a single subcutaneous (sc) injection at the dose of 5 micrograms/kg/d from day 1 after reinfusion of autologous stem cells; rhIL-3 was added from day 6 at the dose of 10 micrograms/kg/d sc (overlapping schedule). ⋯ Our results demonstrated that pretreatment with G-CSF modified the response of BM cells to subsequent stimulation with additional CSFs. The results presented in this paper indicate that in vivo administration of two cytokines increases the proliferative rate and concentration of BM progenitor cells to a greater degree than G-CSF alone. These results support the role of growth factor combinations for accelerating hematopoietic recovery after high-dose chemotherapy.
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Experimental hematology · Dec 1995
A mononuclear cell dose of 3 x 10(8)/kg predicts early multilineage recovery in patients with malignant lymphoma treated with carmustine, etoposide, Ara-C and melphalan (BEAM) and peripheral blood progenitor cell transplantation.
We have assessed the potential use of the mononuclear cell (MNC) content as the sole assessment of graft quality in 35 patients receiving BEAM (carmustine, etoposide, cytosine arabinoside, melphalan) chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation for malignant lymphoma. PBPCs were mobilized with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), and each patient underwent two (n = 20) or three (n = 15) apheresis procedures. Median cell yields were 5.08 x 10(8) MNC/kg (range 1.59-15.70 x 10(8)) and 73.10 x 10(4) CFU-GM/kg (range 0.09-346.72 x 10(4)). ⋯ All patients receiving an MNC dose of > or = 3 x 10(8)/kg achieved neutrophil and platelet recovery by days 12 and 24, respectively. These preliminary data demonstrate that for patients with lymphoma undergoing PBPC mobilization according to this protocol and treatment with BEAM chemotherapy, assessment of MNC dose alone is sufficient to predict early hematologic recovery. Additional assays such as CFU-GM or CD34+ cell counts may not be necessary if this MNC dose is reinfused.