Late onset immune pancytopenia following bone marrow transplantation

Summary:Immune haemolytic anaemia (IHA) is a recognised complication after allogeneic stem cell transplantation (SCT) and occurs more frequently if marrow cells have been subjected to T cell depletion (TCD). Among 58 consecutive patients who underwent TCD-allogeneic SCT from volunteer unrelated donors for the treatment of CML at the Hammersmith Hospital during a 3-year period (1 March 1996 to 28 February 1999) we identified nine cases of IHA. All patients had a strongly positive direct and indirect antiglobulin test and in eight patients the serological findings were typical of warmtype haemolysis often with antibody specificities within the Rh system. All nine cases had clinically significant haemolysis and were treated initially with prednisolone and immunoglobulin. The onset of IHA coincided with the occurrence of leukaemic relapse in six cases, and the presence of host haemopoiesis confirmed by lineagespecific chimerism in all four cases studied. Five patients received donor lymphocyte infusions (DLI); in three molecular remission and the restoration of full donor chimerism coincided with resolution of haemolysis. We conclude that in the context of leukaemic relapse, DLI is an effective therapy for IHA following allografts involving TCD. Bone Marrow Transplantation (2001) 28, 581-586. Keywords: haemolytic anaemia; T cell depletion; chronic myeloid leukaemia; relapse; donor lymphocyte infusion Immune-mediated haemolytic anaemia is a well recognised complication after allogeneic haemopoietic stem cell transplantation (SCT). The majority of reported cases, however, have been alloimmune in origin due to ABO or minor red blood cell antigen incompatibilities between donor and 1,2 and the haemolysis has been short lived due to the rapid consumption of the remaining host cells and/or antibodies. Autoimmune haemolytic anaemia (AIHA) has been reported anecdotally following allogeneic marrow transplantation, primarily in patients transplanted with T cell-depleted (TCD) grafts. [3][4][5] In two large retrospective studies the incidence of AIHA after allogeneic bone marrow transplants was estimated at 3%. 6,7 Both series demonstrated that response to conventional treatment was disappointing and a significant proportion of the patients subsequently died from complications related to AIHA or its treatment.Depletion of T cells from the donor marrow is an effective strategy to reduce the incidence of acute and chronic graft-versus-host disease (GVHD) associated with allogeneic SCT. [8][9][10] Although the incidence of relapse is higher in patients undergoing TCD-SCT compared with recipients of T cell-replete allografts, this can be managed effectively by donor lymphocyte infusions (DLI) which can induce durable complete molecular remissions in more than 70% of patients relapsing after a transplant for CML. 11,12Relapse after allografting for CML is associated with the presence of mixed chimerism (MC) in both myeloid and lymphoid lineages, [13][14][15][16] and a progressive rise in the numbers of BCR-ABL mRNA transcripts dete...

Section: Recipientmentioning

confidence: 99%

Immune haemolytic anaemia following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukaemia: association with leukaemic relapse and treatment with donor lymphocyte infusions

Cwynarski

Goulding

Pocock

et al. 2001

“…20 Although rare, autoimmune pancytopenia has also recently been described in two patients undergoing total lymphoid irradiation (TLI) due to failure to respond to conventional immunosuppressive therapy and splenectomy. 21,22 Patient B only responded to the high-dose dexamethasone which was initiated for the cerebral edema at the peak of her thrombocytopenia during her intracerebral bleed. Although TLI was not used in our patients due to the rapid deterioration in patient A and the rapid sustained response to high-dose steroid in patient B, its early use would be worth considering if conventional measures fail to achieve a prompt response.…”

Section: Discussionmentioning

confidence: 99%

“…Admission platelet count was 7 × 10 9 /l, Hb was 9.9 g/dl and WCC was 4.4 × 10 9 /l. Coagulation studies were normal with international normalised ratio (INR) 1.2 (0.9-1.1) and activated partial thromboplastin time (APTT) 35s (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). Cultures of blood and urine, in particular, viral cultures and antigen for adenovirus from stools were negative.…”

mentioning

confidence: 99%

Acquired autoimmune thrombocytopenia post-bone marrow transplantation for severe combined immunodeficiency

Ting

Ziegler

Vowels

1998

Summary:Children with severe combined immunodeficiency (SCID) have profoundly diminished humoral and cellular immunity resulting in death during infancy unless immune reconstitution occurs by bone marrow transplantation (BMT). Thrombocytopenia post-bone marrow transplantation can be seen in relation to infection, graft-versus-host disease (GVHD) and rarely, as an autoimmune phenomenon due to immune dysregulation. We report two cases of severe AITP following BMT for SCID. Both cases developed large intracerebral hemorrhages from which one died. Autoimmune thrombocytopenia in this setting can be life-threatening and we recommend early and active intervention. Keywords: autoimmune thrombocytopenia; BMT; severe combined immunodeficiency Severe combined immunodeficiency (SCID) is a syndrome describing children with profound cellular and humoral immune dysfunction attributable to different causes such as enzyme deficiencies (ADA, PNP), 1,2 T cell defects, defective HLA expression, as well as the more common ␥c deficiency. 3 For these patients, with the exception of ADA deficiency, bone marrow transplantation (BMT) is the therapy of choice. 4,5 The time taken for engraftment of the marrow cells and immune reconstitution varies depending on multiple factors. These include: (a) the use of T cell depleted 6-8 vs unfractionated bone marrow cells; 9,10 (b) pre-transplant conditioning; (c) the presence or absence of graft-versushost disease (GVHD) and its treatment; 11 (d) concomitant infections; and (e) the general status of the patient. 12 During this early post-transplant period, the immune imbalance observed as the donor immune system emerges, modified by the host, results in well described symptom complexes such as GVHD. 11,[13][14][15][16] This underlying immune dysregulation may also result in autoimmune cytopenias. 12,17 We report two cases of severe AITP following a haploidentical, T cell-depleted allogeneic BMT for SCID. Case report Patient AA girl presented with recurrent respiratory infections and persistent diarrhea and was diagnosed with T − B + SCID with normal adenosine deaminase (ADA) and purine nucleophosphorylase (PNP) levels at 3 months of age. Her hematological and immunological profile at presentation were: hemoglobulin (Hb) 11.8 g/dl, white cell count (WCC) 4.6 × 10 9 /l, platelet count (plat) 225 × 10 9 /l, Ig G/A/M of 1.7, Ͻ 0.1, 0.3 g/l, respectively, CD3 Ͻ0.02 (normal 0.9-1.6), CD4 Ͻ0.02 (normal 0.7-1.2), CD8 Ͻ0.02 (0.3-9.7), CD19 1.74 (0.16-0.36) and NK cells 0.39 (0.13-0.35) × 10 9 /l. Response to mitogen was not performed due to the almost absent number of T cells. She underwent a T cell-depleted (soybean lectin sheep E-rosetting), haploidentical BMT without conditioning from her father at 4 months of age. Engraftment was documented on day +21 post-transplant by fluorescent in situ hybridization (FISH) studies for XY cells and the post-transplantation course was complicated by respiratory failure, acute renal failure and graft-versus-host disease (GVHD) involving skin and gastrointestinal tract...

“…[2][3][4] The incidence of autoimmune haemolytic anaemia in patients who have been allografted in two series was 3.1% 5 and 5% 6 although this may be an underestimate as mild haemolysis may go undetected. This incidence is much higher than Both cold-type and warm-type antibodies have been reported.…”

mentioning

confidence: 91%

Remission of severe, intractable autoimmune haemolytic anaemia following matched unrelated donor transplantation

Pratt

Kinsey

2001

Summary:Immune-mediated haemolytic anaemia presenting post allogeneic bone marrow transplantation is often alloimmune in origin due to ABO or minor red cell incompatibilities. Autoimmune haemolytic anaemia is also recognised, is frequently difficult to treat and overall prognosis is often poor, usually from associated problems. Here, we present a case report of autoimmune haemolysis presenting in an 8-year-old boy 6 months post allogeneic bone marrow transplant requiring 4 years of immunosuppressive therapy before remission of haemolysis. This case report highlights the fact that it is possible for haemolysis to resolve post transplant even after years of immunosuppressive therapy. Bone Marrow Transplantation (2001) 28, 791-793.