Hossam K. Mahmoud

Peripheral blood vs bone marrow as a source for allogeneic hematopoietic stem cell transplantation.

In this randomized prospective study, we included 30 patients with different hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome or severe aplastic anemia) to compare peripheral blood stem cells (PBSC) (15 patients; mean age 23) and bone marrow (BM) (15 patients; mean age 21.8) as a source for allogeneic transplantation regarding the tempo of hematopoietic recovery and the incidence of acute graft-versus-host disease (GVHD). In the BM group, the median nucleated cell count harvested was 1.3 × 1010, while in the PBSC group, the aphereses contained a median of 4.4 × 106 CD34+/kg recipient weight. PBSC transplantation (PBSCT) was associated with faster hematopoietic reconstitution measured as absolute neutrophil count (ANC) >0.5 × 109/l (log-rank P value <0.0018) and platelet count >25 × 109/l (log-rank P value <0.0098). seven patients (46.7%) in the bm group vs only one patient (6.7%) in the PBSC group developed acute GVHD (P = 0.013). Therefore, we conclude that PBSCT is associated with faster hematopoietic recovery and the incidence of acute GVHD does not exceed that seen with BMT.

Special issues related to hematopoietic SCT in the Eastern Mediterranean region and the first regional activity report

Although several centers are now performing allogeneic hematopoietic SCT (HSCT) in the Eastern Mediterranean (EM) region, the availability is still limited. Special issues including compatible donor availability and potential for alternative donor programs are discussed. In comparison to Europe and North America, differences in patterns of diseases and pre-HSCT general status, particularly for patients with BM failure, are described. Other differences including high sero-positivity for CMV, hepatitis B and C infection, and specific observations about GVHD and its relation to genetically homogeneous communities are also discussed. We report that a total of 17 HSCT programs (performing five or more HSCTs annually) exist in 9 countries of the EM region. Only six programs are currently reporting to European Group for Blood and Marrow Transplantation or Center for International Blood and Marrow Transplantation Research. A total of 7617 HSCTs have been performed by these programs including 5701 allogeneic HSCTs. The area has low-HSCT team density (1.56 teams per 10 million inhabitants vs 14.43 in Europe) and very low-HSCT team distribution (0.27 teams per 10 000 sq km area vs <1–6 teams in Europe). Gross national income per capita had no clear association with low-HSCT activity. Much improvement in infrastructure and formation of an EM regional HSCT registry are needed.

Liver disease is a major cause of mortality following allogeneic bone-marrow transplantation.

Background Liver disease is an important cause of morbidity and mortality among recipients of bone-marrow transplantation (BMT). The aim of this retrospective study was to determine the incidence, risk factors and clinical evolution of liver disease following allogeneic BMT. Methods A total of 103 patients (mean age 22.8 years (SD 10.9); 31.1% aged < 18 years; 66% males) transplanted in a single institution were enrolled. Data on donors and recipients were collected, including hematological disease, alanine transaminase, alkaline phosphatase, bilirubin, hepatitis B virus (HBV) and hepatitis C virus (HCV) markers (including HBV-DNA and HCV-RNA). Results Fifty six of 103 patients died, with liver disease the main cause of death (27 of 56, 48%). Overall the incidence of liver failure attributed to hepatic graft-versus-host-disease (GVHD) was 22.3% (23 of 103; 74% HBV/HCV infected) and veno-occlusive disease (VOD) was 9.7% (10 of 103; 80% HBV/HCV infected). Fourteen patients had hepatitis reactivations (four hepatic GVHD and three VOD). Donors’ HCV-RNA status and serum bilirubin above 2 mg/dl were predictive of hepatic GVHD [adjusted odds ratio (AOR) 11.1, 95% confidence interval (CI) 0.99–33.12; AOR 3.93, 95% CI 1.09–14.62; P < 0.05, respectively] and an abnormal alkaline phosphatase could predict severe liver disease (AOR 2.78, 95% CI 1.01–7.54; P < 0.05). Development of severe liver disease (hepatic GVHD or VOD) was a significant predictor of mortality (AOR 4.57, 95% CI 1.09–20.32; P < 0.05) with a low probability of survival (19.3%, SD 7.9%) compared with those without liver disease (52.1%, SD 7.6%; log-rank P = 0.0003). Conclusions Hepatic GVHD is a common complication following BMT and an important cause of liver-related mortality. The high prevalence of HCV and HBV may have contributed to the outcome of hepatic GVHD and VOD. Therefore, antiviral therapy should be considered early to prevent relentless progression of liver disease.

Laminar air flow versus barrier nursing in marrow transplant recipients

SummaryForty-eight patients with acute leukaemia in relapse (n=14), acute leukaemia in complete remission (n=19), chronic myeloid leukaemia (n=8) or severe aplastic anaemia (n=7) received a marrow transplant. The first 26 patients were nursed in laminar-air-flow plastic isolators while the next 22 patients were treated in barrier nursing rooms. Gnotobiotic parameters and morbidity in the 2 groups are compared. Good decontamination of the gastro-intestinal tract was obtained using either of the 2 isolation techniques. The incidence of bacterial and mycotic infections, as well as the supportive care required by the patients was almost equal in both groups. Our results also suggest that the incidence of graft versus host disease may decrease with efficient decontamination of the patients.

Hematopoietic stem cell transplantation in Egypt

Hematopoietic SCT is now an established treatment modality with definitive indications for many hematological disorders. However, this line of treatment requires tremendous resources, and it becomes increasingly difficult for transplanters practicing in the developing world to reconcile the difference between what is possible and what is available. On the basis of 18 years of experience and more than 1300 transplants, this article will focus on special issues, which we think are important for hematopoietic SCT practices in developing countries, taking the program in Egypt as an example that may be applicable to other countries in the developing world. The SCT program in Egypt started in 1989 on a narrow scale. In 1997, the transplant rate increased dramatically with the opening of the SCT unit at the Nasser Institute. Our team is registered in the Center for International Blood and Marrow Transplant Research. The total number of transplants performed till June 2007 is 1362; 80% of the cases are allogeneic and 20% autologous. There are seven other centers in Egypt performing mainly autologous transplants.

Marrow transplantation for pancytopenia in dyskeratosis congenita

SummaryA 33-year-old man with dyskeratosis congenita received a marrow transplant to treat severe pancytopenia. The graft was successful, but the patient developed severe acute graft-versus-host-disease grade IV and died 51 days post-grafting. — The outcome of transplantation in dyskeratosis congenita is compared to that in Fanconis anaemia due to the resemblance of both diseases in some aspects.

Impact of CD34 subsets on engraftment kinetics in allogeneic peripheral blood stem cell transplantation

Summary:Our objective was to evaluate, probably for the first time, the impact of CD34 subsets on engraftment kinetics in allogeneic PBSC transplantation (PBSCT). PBSC graft components were analyzed in 62 cases for the absolute count/kg of total CD34+ and the following subsets: DR− and +, CD71+/−, CD38+/−, CD33+/− and CD61+/−. Time to ANC >0.5 and >1 × 109/l and platelets >20 and >50 × 109/l was reported. The median value for each parameter was used to discriminate rapid from slow engraftment. Four parameters showed significant predictive power of early neutrophil engraftment, namely CD34+/DR− (P=0.002), CD34+/38− (P=0.02), CD34+/CD61− (P=0.04) and total CD34+ cell dose (P=0.04). Four parameters showed significant predictive power of early platelet engraftment, namely CD34+/CD61+ (P=0.02), CD34+/CD38− and total CD34+ cell dose (P=0.04) and CD34+/CD71− (P=0.05). Comparing patients who received >to those who received < the threshold dose(s), only CD34+/CD38− lost its significance for neutrophil engraftment; and only CD34+/CD61+ retained its significance for platelet engraftment (P=0.03); furthermore, the former group required significantly fewer platelet transfusions (P=0.018). We concluded that in allogeneic PBSCT, the best predictor of early neutrophil engraftment is the absolute CD34+/DR− and for early platelet engraftment is the absolute CD34+/CD61+ cell dose.

The «clostridial effect» of selective decontamination of the human gut with trimethoprim/sulphamethoxazole in neutropenic patients

SummaryDuring 59 periods of hospitalisation, 39 patients with either acute myeloid leukemia (22), acute lymphatic leukemia (9), acute undifferentiated leukemia (1), blastic crisis of chronic myeloid leukemia (6) or high-grade malignant non-Hodgkin lymphoma (1) were subjected to aggressive polychemotherapy after selective decontamination of the gut. The patients were given an amphotericin B suspension in a dosage of 1.2 g/day for two days, after which one tablet of trimethoprim/sulphamethoxazole (TMP/SMZ) (160 mg TMP and 800 mg SMZ) t.i.d. was added to prevent endogenous infections by gram-negative aerobic bacteria or moulds and to maintain the “colonisation resistance” endowed by the anaerobes. During 16 of the 59 periods of hospitalisation, no potentially pathogenic aerobic bacteria were isolated, TMP/SMZ-resistantEscherichia coli were the etiological agent of septicemia in two patients, and resistantKlebsiella pneumoniae andPseudomonas aeruginosa in two other patients. These bacteria were cultured from the patients fecal samples prior to the development of septicemia. We observed that long-term prophylaxis with TMP/SMZ modified the normal aspect of the fecal biotop culture, not only by suppressing the aerobic gram-negative bacteria, but also by allowing certain clostridia to appear. We differentiated 207 clostridia from the fecal samples of 29 patients and observed a predominance of TMP/SMZ-resistantClostridium difficile, Clostridium innocuum andClostridium clostridiiforme. C. difficile was also isolated from the blood culture of a neutropenic patient treated with TMP/SMZ and proved to be very toxic in the Verocell culture.ZusammenfassungWährend 59 Krankenhausaufenthalten wurden 39 Patienten nach selektiver Dekontamination des Darmes einer aggressiven Polychemotherapie unterzogen. 22 Patienten litten an akuter myeloischer und neun an akuter lymphatischer Leukämie, ein Patient an akuter undifferenzierter Leukämie, sechs Patienten befanden sich in der Blastenkrise einer chronischen myeloischen Leukämie und einer litt an Non-Hodgkin-Lymphom von hohem Malignitätsgrad. Die Patienten erhielten Amphotericin B Suspension 1,2 g/die, nach 2 Tagen zusätzlich Trimethoprim/Sulphamethoxazol (TMP/SMZ) 3×1 Tabl./die (160 mg TMP und 800 mg SMZ), um endogene Infektionen durch gramnegative Aerobier und Pilze zu verhüten und um gleichzeitig die „colonisation resistance“, die durch Anaerobier gegeben ist, zu erhalten. Während 16 von 59 Krankenhausaufenthalten konnten keine potentiell pathogenen aeroben Bakterien isoliert werden. TMP/SMZ-resistenteEscherichia coli verursachten eine Sepsis bei zwei Patienten, resistenteKlebsiella pneumoniae undPseudomonas aeruginosa bei zwei anderen. Diese Keime wurden aus den Stuhlproben der Patienten gezüchtet, schon bevor sich die Sepsis entwickelte. Wir beobachteten, daß die Langzeit-Prophylaxe mit TMP/SMZ die fäkale Biotop-Kultur nicht nur durch das Fehlen der aeroben gramnegativen Darmbakterien veränderte, sondern auch durch das Aufkommen bestimmter Clostridien. Wir differenzierten 207 Clostridien in Stuhlproben von 29 dieser Patienten und beobachteten das gehäufte Vorkommen von Trimethoprim/Sulphamethoxazol-resistentenClostridium difficile, Clostridium innocuum undClostridium clostridiiforme. C. difficile wurde auch aus der Blutkultur einer TMP/SMZ-behandelten Patientin isoliert und erwies sich in der Verozell-Kultur als sehr toxisch.

Allogeneic bone marrow transplantation for acute leukaemia or chronic myeloid leukaemia in the fifth decade of life

To determine the influence of advanced age on long-term survival after allogeneic bone marrow transplantation (BMT), the probability of survival and the frequency of transplantation-associated complications were analysed retrospectively in 20 patients with acute leukaemia (AL) or chronic myeloid leukaemia (CML), who were 40-49 years of age (median 44.5 years) at the time of transplant. The results of this patient group were compared to those of 32 patients aged 30-39 years (median 33.5 years) with AL or CML, who also underwent BMT during the same period of time. The overall actuarial survival of the two age groups was comparable with 44% and 41% at 5.9 and 5.6 years, respectively. Patients with standard risk criteria (i.e. HLA-genotypically identical sibling donor, 1st chronic phase of CML or 1st remission of AL) showed a higher probability of survival in both groups (62% at 5.9 years in older patients and 59% at 5.5 years in younger patients, respectively). In contrast, actuarial survival in patients who underwent BMT at an advanced stage of their disease or with marrow from a partially HLA-compatible donor was significantly inferior (P = 0.04). The cumulative incidence of acute and chronic graft-versus-host disease was low in older patients (27%), who received marrow from an HLA-identical sibling donor. The most frequent cause of death was interstitial pneumonia, occurring in seven of the older patients (35%) and in seven of the younger patients (22%). This difference, however, was not statistically significant. Our results indicate that allogenic marrow transplantation in the fifth decade of life might be associated with a tolerable risk of transplantation-related complications. This treatment modality may therefore be regarded as first-line therapy for patients in 1st remission of AL or first chronic phase of CML, who show a normal performance status. The same applies to older patients in advanced stages of disease, since the results are comparable to those achieved in the younger patient group.

Trends of Hematopoietic stem cell transplantation in the Eastern Mediterranean region, 1984–2007

Hematopoietic stem cell transplantation (HSCT) activity was surveyed in the 9 countries in the World Health Organization Eastern Mediterranean region that reported transplantation activity. Between the years of 1984 and 2007, 7933 transplantations were performed. The number of HSCTs per year has continued to increase, with a plateau in allogeneic HSCT (allo-HSCT) between 2005 and 2007. Overall, a greater proportion of transplantations were allo-HSCT (n = 5761, 77%) compared with autologous HSCT (ASCT) (n = 2172, 23%). Of 5761 allo-HSCT, acute leukemia constituted the main indication (n = 2124, 37%). There was a significant proportion of allo-HSCT for bone marrow failures (n = 1001, 17%) and hemoglobinopathies (n = 885, 15%). The rate of unrelated donor transplantations remained low, with only 2 matched unrelated donor allo-HSCTs reported. One hundred umbilical cord blood transplantations were reported (0.017% of allo-HSCT). Peripheral blood stem cells were the main source of graft in allo-HSCT, and peripheral blood stem cells increasingly constitute the main source of hematopoietic stem cells overall. Reduced-intensity conditioning was utilized in 5.7% of allografts over the surveyed period. ASCT numbers continue to increase. There has been a shift in the indication for ASCT from acute leukemia to lymphoproliferative disorders (45%), followed by myeloma (26%). The survey reflects transplantation activity according to the unique health settings of this region. Notable differences in transplantation practices as reported to the European Group for Blood and Marrow Transplantation over recent years are highlighted.