Learning Objectives: Fellows will learn how to work-up and subsequently manage patients admitted for bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), or their related complications. Fellows will progressively learn to: 1) Indicate stem cell transplantation (allogeneic, autologous) in newly diagnosed and relapsed/refractory patients. 2) Understand principles of HLA typing and donor selection. 3) Choose appropriate donors, taking into account disease, HLA typing, patient and donor-related information. 4) Choose preparative regimens for each patient based on patient and disease-related factors. 5) Recognize and manage common complications of transplantation (febrile neutropenia, infusion-related reactions, mucositis, and neurological and cardiac events). 6) Recognize and manage serious complications of transplantation, including sinusoidal obstructive syndrome (SOS) of the liver, pulmonary hemorrhage, atypical HUS, etc. 7) Understand rationale for choosing a specific immunosuppressive regimen in allogeneic transplantation. 8) Diagnose and stage acute and chronic graft vs. host disease, and understand principles of management. 9) Utilize comorbidity scoring systems in decisions to proceed (or not) with transplantation. 10) Educate patients about potential shortand long-term complications associated with BMT/PBSCT. 11) Perform diagnostic and therapeutic procedures (bone aspirate/biopsy, lumbar puncture, and tap of Ommaya/Hickham catheters with and without intra-thecal chemotherapy), if procedures are performed. May wish to use separate bone marrow biopsy evaluation tool. 12) Work within a multi-disciplinary team to exhibit excellent interpersonal and communication skills, professionalism, and effective hand-offs.

Bone marrow transplant.

Veno-occlusive disease of the liver after high-dose cytoreductive therapy with busulfan and melphalan for autologous blood stem cell transplantation in multiple myeloma patients.

The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of multiple myeloma: An evidence-based review☆

High-dose therapy in multiple myeloma.

This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides a method of inhibiting the growth of tumor cells comprising contacting said tumor cells with an appropriate amount of monoclonal antibody 8H9 or a derivative thereof.

Uses of monoclonal antibody 8h9

A potential problem of autologous transplantation in the treatment of multiple myeloma (MM) is the infusion of tumor cells. CD34+ selection has been used to purge autografts in MM and it is also possible to reduce tumour cell contamination of autografts by cytotoxic drug therapy prior to peripheral blood stem cell (PBSC) collection. To evaluate the effectiveness of a protocol combining multiple cycles of high-dose therapy and CD34+ selection to reduce tumour contamination of PBSC autografts, 34 MM patients were entered on a treatment schedule comprising two sequential cycles of mobilisation, CD34+ selection, and transplantation following high-dose therapy. In the second cycle of mobilisation there was a five-fold reduction in tumour contamination of the stem cell harvest (0.5 × 106/kg) compared with the first cycle (2.5 × 106/kg). In the 97 CD34+ selection procedures performed a median of 185 × 108 mononuclear cells (MNC) were processed yielding a median of 0.98 × 108 CD34+-enriched cells. CD34+ cells were enriched 68-fold from 1.3% to 88.6%. The median yield of CD34+ cells was 42.2%. Following CD34+ selection the tumour cell contamination of the leukapheresis product was reduced by a median of 2.7 logs. This study demonstrates that in multiple myeloma a significant reduction in the malignant contamination of stem cell autografts can be achieved by combining the in vivo purging effect of cytotoxic therapy with in vitro purging by CD34+ selection. Bone Marrow Transplantation (2000) 25, 1175–1184.

CD34 + selection of autologous peripheral blood stem cells for transplantation following sequential cycles of high-dose therapy and mobilisation in multiple myeloma

Background: Even after high dose chemotherapy (HDT) and autologous haemopoietic stem cell transplantation, the majority of patients with multiple myeloma eventually relapse.



Aim:  The aim of the present study was to study the ­feasibility and outcome of delivering a regimen including in vivo and in vitro purging and double HDT in patients with multiple myeloma.



Methods:  Thirty-four patients with advanced multiple myeloma were enrolled in a program of vincristine, doxo­rubicin and dexamethasone chemotherapy, high dose cyclophosphamide/granulocyte macrophage colony stimulating factor (GM-CSF) stem cell mobilisation, CD34 selection of harvested stem cells (in vitro purging), double HDT (cyclophosphamide/epirubicin in the first, busulphan/melphalan in the second) rescued by CD34+-selected cells, the second rescue using cells harvested following the first HDT (in vivo purging) and interferon maintenance.



Results:  Forty-four per cent of patients completed the program. Fifty-three per cent of withdrawals were as a result of insufficient stem cells. This correlated to previous chemotherapy. Therapy-related mortality was 6%. CD34+ selection achieved more than a 2-log reduction of CD38++ cells; in vivo purging achieved 80%. Although similar numbers of CD34+ cells were reinfused at both HDT, platelet recovery was slower after the second HDT. Additional complete remissions were achieved after each phase of therapy, 3% at the end of vincristine, doxorubicin and dexamethasone and 33% after completing planned HDT. Factors associated with longer overall survival included age less than 60 years (P = 0.044), serum β-2-microglobulin below 3 µγ/L at entry (P = 0.042) and less than 2 months between the two HDT (P = 0.024). The only factor associated with a longer event-free survival was less than 2 months between HDT on study (P = 0.038).



Conclusions:  (i) dose intensification with two HDT delivered within 2 months might be associated with a better patient outcome, (ii) early mobilisation should be incorporated in multiple myeloma HDT programs and (iii) higher CD34+ doses may be required for tandem transplants. (Intern Med J 2004; 34: 167−175)

Long-term follow up of sequential mobilisation and autologous transplantation with CD34-selected cells in multiple myeloma: a multimodality approach.

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CD34 + selection of autologous peripheral blood stem cells for transplantation following sequential cycles of high-dose therapy and mobilisation in multiple myeloma

Long-term follow up of sequential mobilisation and autologous transplantation with CD34-selected cells in multiple myeloma: a multimodality approach.