CD34+ selected cells in mismatched stem cell transplantation: a single centre experience of haploidentical peripheral blood stem cell transplantation

Abstract

Over the past 3 years we have performed 10 haploidentical peripheral blood stem cell transplants in patients with incurable haematological malignancies and no prospect of a matched unrelated donor within an adequate time period. Conditioning consisted of ATG, TBI, thiotepa, cyclophosphamide and additional radioimmunotherapy in five patients. All patients received G-CSF mobilized peripheral blood stem cell grafts. GVHD prophylaxis consisted of T cell depletion by CD34+ selection; no post-transplant immunosuppression was given in nine patients. Stable engraftment was achieved in nine patients; one case of acute graft rejection was observed. Seven patients developed grade I acute GVHD, and six patients have developed chronic GVHD. Infections were the most significant clinical problem post transplant. Two patients have suffered a relapse of their disease and two further patients have died of transplant-related complications. After a median follow-up of 13 months (range 5-37 months) six patients are surviving in remission. We conclude that haploidentical PBSCT is a reasonable alternative to a MUD transplant.

Partially matched related donor peripheral blood progenitor cell transplantation in paediatric patients adding fludarabine and anti-lymphocyte gamma-globulin

“…These figures are probably influenced by the use we make of CsA, as we currently administer this immunomodulator while acute GVHD is more likely to occur, but we withdraw it when viral infections are more likely to occur. Some groups do not currently administer CsA as GVHD prophylaxis 5,11,12,15 due to the extensive lymphoid depletion they perform. Finally, according to our results, CD34 cell dose does not seem to influence the incidence of GVHD.…”

“…Most approaches designed to override these complications involve a combination of both ex vivo T cell depletion of the graft plus a final in vivo lymphoid depletion. 5,[7][8][9][10][11][12] These immunosuppressive schedules could be partly responsible for the increased incidence of opportunistic infections reported in PMRD HPT. The most relevant reports on mismatched transplantation are detailed in Table 2, together with their complications and clinical outcomes.…”

“…17,18 Its addition to a standard conditioning regimen 14 could reduce the tendency to rejection associated with PMRD HPT. In addition to fludarabine, the combination of CD34-positive selection and a lymphocyte-toxic gamma-globulin (anti-lymphocyte gamma-globulin (ALG) in our practice), 5,9,11,12 could reduce the risk for severe forms of GVHD.…”

“…Unfortunately, these regimens also interfere with the post-transplant immune reconstitution, therefore increasing the risk of infectious complications. 5,8,9,11 Fludarabine monophosphate is a relatively non-toxic agent that causes severe T cell immunosuppression by inhibiting adenosine deaminase. 16 This purine analogue is currently used to provide immune tolerance in other clinical settings.…”

“…[2][3][4][5][6][7][8][9] However, more recent reports have suggested otherwise. [10][11][12][13][14][15] In most of these reports, the conditioning regimens consist of potent immunosuppressive combinations intended to increase immune tolerance. Unfortunately, these regimens also interfere with the post-transplant immune reconstitution, therefore increasing the risk of infectious complications.…”