Mobilization of predominantly Philadelphia chromosome‐negative blood progenitors using cyclophosphamide and rHUG‐CSF in early chronic‐phase chronic myeloid leukaemia: correlation with Sokal prognostic index and haematological control

Abstract

Summary. Mobilization of Philadelphia chromosome (Ph) negative blood progenitors was attempted in 23 newly diagnosed chronic myeloid leukaemia (CML) patients using a regimen of cyclophosphamide (CY) 5 g/m 2 and rHUG-CSF 150 mg/m 2 daily. This regimen was well tolerated with no major adverse events reported. More than 2 × 10 6 /kg CD34 þ cells were collected in 21 patients (91%). Predominantly Ph-negative mobilization (0-25% Ph-positive) was seen in 30% of cases overall and was confined to patients with a Sokal prognostic score < 1 (7/11 with Sokal score <1; 0/12 with Sokal score у1). Within the low Sokal index group, a low WBC count pre-mobilization and a low WBC nadir both correlated strongly with Ph-negative mobilization (P ¼ 0 . 006 and 0 . 02 respectively). Five of 19 patients receiving at least 6 months of Roferon A therapy post mobilization achieved a major cytogenetic response; all five patients were Ph-negative mobilizers. Therefore CML patients can be divided into a good-prognosis group in whom predominantly Ph-negative progenitors can be mobilized using a regimen of moderate intensity if haematological control is achieved pre-mobilization, and a poorprognosis group for whom predominantly Ph-positive cells are mobilized with this regimen regardless of haematological control.

Collection of Philadelphia-negative peripheral blood progenitor cells in unselected patients with chronic granulocytic leukaemia

“…This has been achieved using a regimen causing no mortality and acceptable morbidity. The ability to mobilize adequate numbers of haemopoietic progenitor cells for engraftment appears to be significantly associated with the patients' Sokal score at diagnosis confirming the observation by Hughes et al 26 who failed to achieve a successful harvest in any patient with a Sokal score Ͼ1.0. In contrast, Carella et al 27 using a more intensive mobilising regimen (idarubicin, cytosine arabinoside and etoposide (ICE)) found no association between achievement of a successful harvest and Sokal score at diagnosis.…”

“…Analysis of 30 metaphases cannot exclude a clone of up to 10% Ph-positive cells at the 95% confidence limit. 32 Other studies 13,26,31 are based on the analysis of 20 metaphases (clones of up to 14% Ph-positive cells cannot be excluded). Such variation in the number of metaphases examined could go some way towards explaining the apparently lower levels of completely Ph-negative collections in this study.…”

“…The true potential of this regimen in larger numbers of newly diagnosed patients remains to be evaluated. Hughes et al 26 have mobilized 75-100% Ph-negative cells in at least one leukapheresis in seven of 21 evaluable patients using high-dose cyclophosphamide and GCSF. This regimen caused no mortality and tolerable morbidity.…”

“…Total registration of all new cases of CGL has been in place since January 1988. A median of 25 new cases present per annum (range [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. 4 From January 1994 a programme of early intervention for patients under 60 years of age was begun with the cooperation of all 25 regional haematologists.…”

Mobilisation of haemopoietic progenitors in CML: a second course of intensive chemotherapy does not improve Ph-negativity in stem cell harvests

“…A substantial portion of patients treated in this way revert, at least temporarily, to Ph-negative haemopoiesis. [9][10][11][12][13][14][15][16][17][18][19] The probability of reaching a major cytogenetic reponse after autoSCT may be related to the number of negative progenitors in the stem cell graft. 20 Generally, haemopoietic stem cells have been harvested in the early recovery phase after a single cycle of conventional intensive chemotherapy followed by G-CSF.…”