Reduced-toxicity conditioning with fludarabine and treosulfan prior to allogeneic stem cell transplantation in multiple myeloma.

In recent years, reduced-intensity conditioning (RIC) regimens before allogeneic stem cell transplantation (SCT) are increasingly used in patients not eligible for conventional conditioning. We did a retrospective, multicenter analysis to assess the feasibility of conditioning with fludarabine and treosulfan before allogeneic SCT in multiple myeloma patients. Thirty-four patients with a median age of 51.5 years were included in the analysis. All patients underwent myeloablation after conditioning followed by stable engraftment, and 29 of 31 evaluable patients (94%) showed early complete hematopoietic chimerism. Non-hematological toxicities were limited and encompassed mainly fever in neutropenia and infections. Grade II-IV acute and chronic graft-versus-host disease was observed in 33 and 39%, respectively. With a median follow-up of 708 days (range 60-1729 days), the median progression-free survival was 180 days. The treatment-related mortality was 10% on day 100 and 25% after 1 year. The median overall survival has not yet been reached. Our data indicate that conditioning with fludarabine and treosulfan before allogeneic SCT is feasible in intensively pretreated multiple myeloma patients and leads to stable engraftment and complete hematopoietic chimerism. Randomized trials are warranted to determine if this approach might be incorporated in an algorithm of multiple myeloma treatment.

Allogeneic hematopoietic cell transplantation following conditioning with 90Y-ibritumomab-tiuxetan.

Radioimmunotherapy (RIT) of relapsed lymphoma is gaining increasing importance. Especially the commercially available anti-CD20 antibody 90Y-ibritumomab tiuxetan is currently under investigation in various trials including dose escalation and autologous hematopoietic progenitor cell support. It is not clear, however, whether the implementation of this radiolabeled antibody into another treatment option for relapsed or poor risk lymphoma patients-allogeneic hematopoietic cell transplantation-interferes with or delays successful engraftment. This study reports encouraging results with 2 relapsed lymphoma patients (1 transformed marginal zone lymphoma and 1 mantle cell lymphoma) who underwent allogeneic hematopoietic cell transplantation from HLA-matched donors. The conditioning regimen consisted of Rituximab 250 mg m(-2) on days -21 and -14, 0.4 mCi kg(-1) body weight 90Y-ibritumomab tiuxetan on day -14 and fludarabine (30 mg m(-2)) plus cyclophosphamide (500 mg m(-2)) on days -7 to -3. The data demonstrate that engraftment is fast and reliable with leukocytes >1 x 10(9) L(-1) on day 12 and platelets >50 x 10(9) L(-1) on day 10. Thus, the incorporation of radioimmunotherapy into allogeneic transplant protocols combines established modalities with proven anti-lymphoma activity and, hence, offers an attractive new therapeutic option for relapsed lymphoma patients.

[Hyperexpression of the multiple drug resistance gene (MDR-1) in chronic myeloleukemia patients]. / Giperékspressiia gena mnozhestvennoi lekarstvennoi ustoichivosti (MDR-1) u bol'nykh khronicheskim mieloleikozom.

AIM: To elucidate prognostic value of MDR-1 gene expression in patients with chronic myeloid leukemia (CML). MATERIALS AND METHODS: The MDR-1 gene expression was studied by in situ hybridization in hemopoietic cells of 63 Ph-positive CML patients in different phases of the disease. The survival of the patients and duration of the chronic phase (CP) were evaluated using the Caplan-Meyer method. RESULTS: MDR-1-positive patients had a shorter survival (p < 0.01) and CP (p < 0.05) than negative ones. MDR-1 gene overexpression has no impact either on the survival or duration of AP and BP (p < 0.05). Moreover, the MDR-1 gene overexpression is not dependent either on the previous treatment or other prognostic markers. CONCLUSION: Overexpression of MDR-1 gene is an independent prognostic factor and an additional parameter to Sokal's scores.

[A trial of using allogeneic bone marrow transplantation in children with different hematologic neoplastic diseases]. / Opyt primeneniia allogennoi transplantatsii kostnogo mozga u detei s razlichnymi onkogematologicheskimi zabolevaniiami.

AIM: To define optimal time for transplantation of bone marrow (TBM) in children with hematological malignancies. MATERIALS AND METHODS: 20 allogenic TBMs were performed in children with acute myeloblastic leukemia (6 patients, 2 of them in recurrence), acute lymphoblastic leukemia (7 patients, 4 of them in recurrence), chronic myeloid leukemia (CML) in a chronic stage (3 patients), severe aplastic anemia (3 patients), generalized neuroblastoma (1 patient). Pretransplantation preparation included cyclophosphamide and busulphane or cyclophosphamide, busulphane and vepezide. The graft-versus-host reaction (GVHR) was prevented with cyclosporin A plus methotrexate or cyclosporin A plus urbazone. Engrafting was recognized by change of karyotype and blood group. RESULTS: From 13 children with acute leukemia subjected to TBM in a complete remission 4(33%) are alive, 5 died within 100 days after TBM (TBM was made in recurrence in 4 children), 3 patients died of recurrence 12 months after TBM. One patient with CML and one with severe aplastic anemia remain in remission. The main complications and causes of death in early posttransplantation period were hemorrhagic syndrome, infectious complications, GVHR. According to a one-year follow-up, the recurrent disease caused death most frequently. CONCLUSION: Positive result of TBM is related to the disease stage at transplantation.

[The effectiveness of interferon-alpha therapy in Ph-positive chronic myeloid leukemia]. / Effektivnost' interferon-alpha terapii u bol'nykh Ph-pozitivnym khronicheskim mieloleikozom.

Chronic myeloid leukemia (CML) is a hemopoietic condition caused by chromosomal translocation t(9;22)(q34;q11) or bcr-abl fusion gene. The predominant variants of bcr-abl oncogene rearrangement are b3a2 and b2a2. The present study evaluated the efficacy of interferon-a therapy of CML patients and molecular prognostic factors. Cytogenetic response and complete hematological remission were more frequent in CML b3a2 treatment with interferon-a. Moreover, after therapy, chronic phase lasted in that group (p = 0.026) much longer. Overall survival in the group was significantly longer, too (p = 0.046).

[Detection of chromosome translocation t(9;22) using RT-PCR]. / Vyiavlenie khromosomnoi translokatsii t(9;22) metodom RT-PTSR.

The investigation deals with a simplified modification or molecular-genetic detection of translocation t(9;22) using a combination of reverse transcription and polymerase chain reactions (RT-PCR). Unlike the available protocols, analysis is carried out using one enzyme--TET-Z polymerase--(instead of two) which has both revertase and DNA-polymerase activities. The present modification is highly sensitive, less time-consuming and cheaper. The method has proved useful for both diagnosing t(9;22) translocation and diagnosing and monitoring minimal residual disease remaining after marrow transplantation.